Fysisk Aktivitet og Sundhed fra teori til praksis. Bente Klarlund Pedersen Rigshospitalet

Transkript

1 Fysisk Aktivitet og Sundhed fra teori til praksis Bente Klarlund Pedersen Rigshospitalet

2 Årligt antal dødsfald relateret til forskellige til forskellige risikofaktorer risikofaktorer Rygning Kort uddannelse Inaktivitet Alkohol Højt blodtryk For lidt frugt og grønt For meget mættet fedt Arbejdsbetingede lid. Passiv rygning Hjemme- og fritidsulyk Træffer sjældent familie Psyk arbejdsbelastning Overvægt Stofmisbrug Ingen hjælp fra andre Trafikulykker Usikker sex Arbejdsulykker Årligt antal dødsfald relateret Juel et al. Risikofaktorer og folkesundhed. SIF 2006

3 Det Obesity Amerikanske Trends* Among Paradoks: U.S. Adults de spiser mindre BRFSS, og mindre, 1990, 1999, men 2008bliver federe og (*BMI 30, or about 30 lbs. overweight for 5 4 person) 1990 federe No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

4 Små forskydninger i energibalancen 1 bolsje mere = 500 skridt mindre = 20 kcal per dag

5 1 bolsje mere = 500 skridt mindre = 20 kcal per dag = 10 kg vægtøgning på 10 år

6 Det ubevidste

7 Vi ved, at Colaflaskerne er større i dag end da vi var børn..

8 ..men reelt er vi ikke i stand til at registrere daglige udsving i energiindtag på mindre end 20%.

9 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal

10 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal

11 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal 200 kcal

12 Vi spiser det, der er på tallerkenen

13

14 Forsøgspersoner, der spiste af de bundløse suppetallerkener, spiste markant mere end de forsøgspersoner, der tømte deres tallerken på normal vis.

15 Vi spiser det, vi har besluttet os for

16 I den ene halvdel af rummet blev de afgnavede kyllingeben fjernet og studenterne fik rene tallerkener.

17 I den anden halvdel af rummet hobede vingebenene sig op.

18 De studenter, der hele tiden fik rene tallerkener og altså ikke blev mindet om, hvor meget de havde spist, spiste markant mere.

19 Hvis man skifter store tallerkener ud med mindre tallerkener, spiser man mindre.

20 Hvis vi skifter brede glas ud med smalle glas, drikker vi mindre.

21

22

23 Vi spiser ofte én af hver.

24 Vi går efter variation

25 Vi er bevidste om økologi, fedtindhold, sukkerindhold og farvestoffer. Men vi har en markant ubevidst adfærd, når det gælder de mængder, vi spiser.

26 Tilgængelighed Synlighed Variation er vigtige eksterne faktorer, når det gælder den mængde mad, vi spiser

27 .. vi er heller ikke i stand til at registrere daglige udsving i energiforbrug på mindre end 20%.

28 Bettina er sådan en person, som mange kvinder misunder i deres stille sind. Jeg vil vædde på, at hun er født med det og aldrig har haft brug for at gå på diæt i hele sit liv. Og det var lige præcist sådan det var, lige indtil hun faktisk ikke længere var helt så slank, som hun plejede at være.

29 Bettinas havde ingen bil, hun boede i København og gik hver dag fra sit hjem til sit arbejde. Det tog ca. 30 minutter.

30 Bettina og Jakob finder en lejlighed og flytter sammen.

31 Bettina forstod simpelthen ikke hvorfor hun begyndte at lægge sig ud.

32 Bettina havde tidligere deltaget i en skridttællerkonkurrenc e og vidste, at hun normalt gik skridt om dagen.

33 Da hun atter fik en skridttæller på, viste den, at hun gik skridt om dagen.

34 En reduktion på skridt om dagen svarede for Bettina til et dagligt mindre kalorieforbrug på 200 kalorier svarende til en vægtøgning på ca. 5 kg på et halvt år.

35 200 kcal om dagen = 10 kg på 1 år = 50 kg på 5 år

36 200 kcal om dagen = 10 kg på 1 år = 50 kg på 5 år

37 200 kcal om dagen = 10 kg på 1 år = 50 kg på 5 år

38 200 kcal om dagen = 10 kg på 1 år = 50 kg på 5 år

39 200 kcal om dagen = 10 kg på 1 år = 50 kg på 5 år

40 Det Obesity Amerikanske Trends* Among Paradoks: U.S. Adults de spiser mindre BRFSS, og mindre, 1990, 1999, men 2008bliver federe og (*BMI 30, or about 30 lbs. overweight for 5 4 person) 1990 federe No Data <10% 10% 14% 15% 19% 20% 24% 25% 29% 30%

41 Cuba i 90`rne: Færre døde af livsstilssygdomme! Mens den vestlige verden oplever en fedme-epidemi med stigende forekomst af type 2 diabetes, har udviklingen været stikmodsat i Cuba.

42 Cuba i 90`rne: Færre døde af livsstilssygdomme! Cubas økonomiske krise resulterede i reduceret energi-indtag øget fysisk aktivitet. Franco et al. Obesity reduction and its possible consequences: what can we learn from Cuba's Special Period? CMAJ Apr 8;178(8):1032-4

43 Krisen medførte et reduceret gennemsnitligt kalorieindtag fra 2,899 kalorier til 1,863 kalorier per dag Kalorier Før Under

44 Antallet af fysisk aktive blev øget fra 30% til 67% % fysisk aktive Før Under

45 I gennemsnit havde den enkelte borger et vægttab på 5 kg. Forekomsten af fedme faldt fra 14% to 7% % fede Før Under

46 Fald i dødsfald i løbet af som følge af diabetes Før Under %

47 Fald i dødsfald i løbet af som følge af hjertesygdom Før Under %

48 Fald i dødsfald i løbet af som følge af død af alle årsager Før Under %

49 Erfaringerne fra Cuba indicerer, at strukturelle ændringer i et samfund, der understøtter mindre energiindtag og større fysisk aktivitet kan have markant effekt på sygdom og død.

50 Tilgængelighed Synlighed Variation er vigtige eksterne faktorer, når det gælder vores fysiske aktivitets niveau i dagligdagen.

51 Er Julia Roberts nødvendigvis blevet mindre usund med en vægtøgning på 50 kg?

52 -effekt på tidlig død 2 1 Sløv Sedentary 0 Fat Slank Slim Fed Fit Fit Stevens J et al Int J Obes Relat Metab Disord 2004; 28(11):

53 Hellere Fed og Fit end Slank og Sløv 2 1 Sløv Sedentary 0 Fat Slank Slim Fed Fit Fit Stevens J et al Int J Obes Relat Metab Disord 2004; 28(11):

54 Inflammation

55 Conjunctivitis

56 Meningococci infection

57 Meningitis

58 Pulmonary Tuberculosis

59 Glandular Tuberculosis

60 Leprosy

61 Syphilis, 1.stage

62 Syphilis, 2.stage

63 Syphilis, 3. stage

64 Sepsis

65 Inflammation er et dobbeltægget sværd!

66 Sammenfald af Sygdomme Hjertesygdom Type 2 diabetes Højt blodtryk Depression Demens Tarmkræft Brystkræft

67 Kronisk Inflammation Hjertesygdom Type 2 diabetes Højt blodtryk Depression Demens Tarmkræft Brystkræft

68 Fysisk Aktivitet som for Forebyggelse Hjertesygdom Type 2 diabetes Højt blodtryk Depression Demens Tarmkræft Brystkræft

69 Fysisk Aktivitet som for Behandling Hjertesygdom Type 2 diabetes Højt blodtryk Depression Demens Tarmkræft Brystkræft

70

71

72 Fysisk aktivitet hæmmer inflammation

73 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

74 Physical Activity Myokines Abdominal Adiposity Chronic Inflammation

75 Infiltration of immune cells into white adipose tissue, and subsequently local inflammation in fat tissue, is correlated with the development of insulin resistance and type 2 diabetes

76 Matter CM, Handschin C. RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), Inflammation, Obesity, and the Metabolic Syndrome. Similarly, activated immune cells and inflammation have an important role in cardiovascular diseases Haffner SM. The Metabolic Syndrome: Inflammation, Diabetes Mellitus, and Cardiovascular Disease. The American Journal of Cardiology 2006 Jan 16;97(2, Supplement 1):3-11.

77 Moreover, Alzheimers disease are linked to local inflammation in the brain and systemic inflammation appears to exacerbate the progression of this diseases

78 An increase in the levels of circulatory inflammatory cytokines is involved in the initiation of tumour growth Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. Journal of Clinical Investigation 2007;117(5): Zhou JR, Blackburn GL, Walker WA. Symposium introduction: metabolic syndrome and the onset of cancer. Am J Clin Nutr 2007 Sep;86(3):s817-s819.

79

80 Christoph Handschin & Bruce M. Spiegelman Nature 454, (24 July 2008)

81 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

82 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

83 Healthy females n = years - risk for cardiovascular disease effect of walking Manson et al, N Engl J Med Sep 5;347(10): ,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0, , >10

84 Healthy females n = years - risk of cardiovacsular disease effect of walking 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 BMI < 25 BMI ,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0, ,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0 BMI > 30

85 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

86 Abdominal fat reflects accumulation of visceral fat

87 Ectopic fat includes Visceral fat, fat in the muscle, in the liver and around large vessels

88 Abdominal adiposity is associated with both cardiovascular disease, Type 2 diabetes, and dementia. Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB. Abdominal Obesity and the Risk of All- Cause, Cardiovascular, and Cancer Mortality: Sixteen Years of Follow-Up in US Women. Circulation 2008 Apr 1;117(13): Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. J Endocrinol Invest. 2006;29(3 Suppl): Review

89 Abdominal adiposity is directly associated with all-cause mortality independently of body mass index (BMI), even in people with a normal body weight

90 BMI and Mortality Hu et al N Engl J Med 2004; 351:

91 Association of WHR within BMI categories with MI risk INTERHEART participants Yusuf et al Lancet 2005;366:1640

92 Risk of MI in relation to waist and hip circumference the INTERHEART study Waist Hip

93 8-year progression of aortic calcification in women with different forms of body fat distribution: 290 postmenopausal females out of 1356 subjects DEXA scan 8-year change in AC 4 3 * Tanko et al 2003 Eur Heart J 24:

94 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

95 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

96

97 Fra til skridt per dag i 14 dage

98 Kondital Fitness 25,8 25,7 25,6 25,5 25,4 25,3 25,2 25, ,9 Vo2max 7% Before After

99 Vægt Body Weight 70,4 70, ,8 69,6 69,4 69, ,8 68,6 Body Weight 1.2 kg Before After

100 Total Muskelmasse Total Muscle Mass 55 54,8 54,6 54,4 54, ,8 53,6 53,4 53,2 53 Total Muscle Mass 1.2 kg Before After

101 Total Fedtmasse Total Fat Mass Before After Total Fat mass

102 Fedt mellem Total Fat Mass de indre organe 750 7% Before After Abdominal fat

103 MR-scanning viser fedtet mellem de indre organer efter 14 dages inaktivitet Før Efter

104 MR-scanning viser fedtet mellem de indre organer efter 14 dages inaktivitet Før Efter

105 MR-scanning viser fedtet mellem de indre organer efter 14 dages inaktivitet Før Efter

106 Konc. [micromol/l] Fedtbelastningstest OFTT - p-tag 2500, , , ,00 500,00 0, Preinactivity time [hours] Postinactivity

107 pmol/l Sukkerbelastningstest Plasma Insulin 600,00 500,00 400,00 300,00 200,00 OGTT before OGTT after 100,00 0, Time (min)

108 Tab af muskelmasse Tab af fitness Bugfedme Tab af insulinfølsomhed

109 Tab af muskelmasse Tab af fitness Tab af insulinfølsomhed

110 Visceral Fat Distribution: Normal vs Type 2 Diabetes Normal Type 2 Diabetes

111 Visceral fat is more inflammed than subcutaneous fat and visceral fat contributes to systemic inflammation Normal Type 2 Diabetes

112 Macrophage inflammation of adipose tissue Weisberg et al J Clin Invest 2003;112:1796 Xu et al J Clin Invest 2003;112:1821 Curat et al Diabetes 2004;53:1285

113 Myokines We have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibers and exert either paracrine or endocrine effects should be classified as 'myokines' Pedersen BK & Febbraio M, Physiological Reviews 2008

114 Physical Activity Myokines Abdominal Adiposity Chronic Inflammation

115 From Man to Molecule? IL-15??

116 IL-15 a molecule involved in muscle-fat cross talk? IL-15 IL-15R IL-15 IL-15 IL-15R IL-15R

117 Trunk fat mass R 2 = Plasma IL-15 Inverse relationship between plasma-il- 15 and visceral fat mass

118 Overexpression of IL-15 in murine muscle

119 Visceral fat/body weight (mg/g) Overexpression of in skeletal muscle - effect on visceral fat mass Controls IL Control IL * Normal * High-fat

120 Muscle IL-15 protein (relative to pre) Young healthy males performed high-intense cycle training for 12 weeks Muscle IL-15 protein 2 Control Trianing * 1 0 Pre Nielsen AR et al, unpublished data Post

121 IL-15 IL-15 IL-15 may be involved in a muscle-to-fat endocrine axis which modulates body composition IL-15R IL-15R IL-15 IL-15R

122 ? IL-15??

123 Pedersen BK, Febbraio M, Physiol Reviews 2008

124 -1 R a F A (µ m o l.kg.m in -1 ) -1 R F A (µ m o l.k.m g in -1 ) d Rate of disappearance of Fatty Acids 14 Rate of appearance of Fatty Acids #& #& #& #& & #& # & #& # & #& #& #& #& rhil-6 infusion #& #& #& #& T im e (m in ) #& #& # & #& rh Il-6 in fu s io n # & #& T im e (m in ) C o n Low -rhil6 H ig h -rh IL 6 Van Hall et al, J Clin Endocrinol Metab June 2003 C o n L o w -rh IL -6 H ig h -rh IL 6 Van Hall et al, J Clin Endocrinol Metab June 2003

125 GIR (mg.kg -1.min -1 ) GIR (mg.kg -1.min -1 ) IL-6 enhances insulin-stimulated glucose uptake in humans * Carey et al Diabetes 2006

126 Pedersen BK, Febbraio M, Physiol Reviews 2008

127 In vivo model of low-grade inflammation in humans

128 Endotoxin-induced increase in plasma-tnf 4 3,5 3 2,5 2 1,5 1 0,5 Endotoxin ANOVA: P=0.001 Rest 0 IL-6 0 Starkie et al FASEB J 2003 Rest h

129 Endotoxin-induced increase in plasma-tnf 4 3,5 3 2,5 2 1,5 1 0,5 Endotoxin ANOVA: P=0.001 Rest Exercise IL-6 0 Exercise h

130 Endotoxin-induced increase in plasma-tnf 4 3,5 3 2,5 2 1,5 1 0,5 0 Endotoxin IL-6 infusion h ANOVA: P=0.001 Rest Exercise IL-6

131

132 Physical Inactivity Abdominal Adiposity Chronic Inflammation Insulin Resistance

133 Er Julia Roberts nødvendigvis blevet mindre usund med en vægtøgning på 50 kg?

134

135 Sammenfald af Sygdomme Hjertesygdom Type 2 diabetes Højt blodtryk Depression Demens Tarmkræft Brystkræft

136 Energi Stress Angst Humør Koncentration Libido

137

138 Skuespilleren Birthe Neumann jeg husker den første dag, hvor jeg får udgangstilladelse. Det er en meget, meget varm dag. Jeg går op ad Nordre Fasanvej, og så er det, at jeg hører musik. På denne stillestående varme sommersøndag eftermiddag, hører jeg pludselig, at nogen spiller Rock Around The Clock Tonight: One, two three o`clock, four o`clock rock..

139 Jeg går efter musikken. Gennem et vindue ser jeg så dette hold af kvinder, der danser til musikken. Klædt i pink, gul, koboltblå i virkeligheden meget stærkere farver end jeg kunne tåle. Men jeg var draget. Det var kvinder på min alder eller yngre eller ældre, som dyrkede aerobics for fuld udblæsning. Og så var det, jeg vidste, at det var det, jeg skulle.

140 Så du begynder at gå i fitness-center?

141 Ja, jeg dyrker hård konditionstræning i form af aerobics. Ikke 1 time ad gangen, men to timer i træk. Hver dag. Og ofte både formiddag og eftermiddag.

142 Og hvad sker der forsvinder depressionen og tvangstankerne, mens du laver aerobics?

143 Nej, slet ikke. Jeg kan have de forfærdeligste tanker, mens jeg hopper rundt. Det er bagefter det sker. Når jeg rigtigt har svedt og bagefter står under bruseren og senere smører min krop ind i lotion, så er det, at jeg får denne utrolige følelse af velvære. Desværre varer denne følelse ikke ved særlig længe. Men det er dette kick af velvære og nydelse, som jeg stræber

144 Joggers high

145

146 ? Betaendorfin Noradrenalin Serotonin Dopamin BDNF

147 ? Betaendorfin Noradrenalin Serotonin Dopamin BDNF

148 ? Betaendorfin Noradrenalin Serotonin Dopamin BDNF

149 Utrænet muskel Trænet muskel præstation

150 Utrænet muskel Trænet muskel Sundhed

151 Utrænet muskel Trænet muskel Samme mekanismer

152

153 VO2max Untrained Trained

154 Flere små blodkar Trænet Trænet Andersen P and Henriksson J. Capillary supply of the quadriceps femoris muscle of man: adaptive response to exercise.

155 Flere mitokondrier = energistationer

156 bedre til at lagre glykogen i musklerne Gollnick PD and Saltin B. Significance of skeletal muscle oxidative enzyme enhancement with endurance training. Clin Physiol 2: 1 12, 1982 Hawley JA. Adaptations of skeletal muscle to prolonged, intense endurance training. Clin Exp Pharmacol Physiol 29: , 2002 Holloszy JO and Booth FW. Biochemical adaptations to endurance exercise in muscle. Annu Rev Physiol 38: , 1976 Mitchell JB, Costill DL, Houmard JA, Flynn MG, Fink WJ, and Beltz JD. Influence of

157

158 O 2 ml/min RQ 0.91 FFA TAG Glycogen Fat RQ 0.82 FFA TAG Fat 200 CHO Glycogen 100 Glucose Glucose CHO min Utrænet 120 min Trænet

159 Exercise-induced Exercise-induced gene gene activation activation in in human human skeletal skeletal muscle muscle 0 0 3h 3h 6h 6h 9h 9h 24h 24h

160 Ex-0h-AL1 ** Ex-3h-AL4 ** Ex-6h-AL6 ** Ex-9h-AL7 ** Ex-24h-AL8 ** fatyacidbindingprotein3,muscleandheart tumorsupresordeletedinoral cancer-related1 heatshockprotein,alpha-crystalin-related,b6 carboxylesterase2(intestine,liver) glutaredoxin(thioltransferase) al-trans-13,14-dihydroretinol saturase cholinergicreceptor,nicotinic,alphapolypeptide1(muscle) purinergicreceptorp2x,ligand-gatedionchanel,5 colagen-liketail subunitofasymetricacetylcholinesterase angiomotinlike1 signal-inducedproliferation-asociated1like2 isocitratedehydrogenase3(nad+)alpha solutecarierfamily25(carnitine/acylcarnitinetranslocase),member20 mitochondrial protein18kda myosinbindingproteinh humanimuneasociatednucleotide6 Zincfingerprotein302 DNA-damage-inducibletranscript4-like Plasminogen-like growthdiferentiationfactor8 eukaryotictranslationinitiationfactor4a,isoform2 Thyroidhormonereceptorasociatedprotein1 Dystrobrevin,alpha Titinimunoglobulindomainprotein(myotilin) Semaphorin6D carbonicanhydraseiv regucalcingenepromotoregionrelatedprotein Dsiteofalbuminpromoter(albuminD-box)bindingprotein nuclearfactornf-kapa-binhibitoralpha Neuroserpin LIMdomainbinding2 thyroidhormonereceptor,alpha DAPK-interactingprotein1 Zincfinger,MYNDdomaincontaining17 synaptotagmin-like3 ankyrinrepeatdomain20a flavincontainingmonoxygenase2 CXCfinger6 Phosphonoformateimuno-asociatedprotein5 RAR-relatedorphanreceptorA dual specificityphosphatase10 Myocytenhancerfactor2C myosinx syntaxinbindingprotein6(amisyn) WDrepeatandSOCSbox-containing1 ectonucleotidepyrophosphatase/phosphodiesterase2(autotaxin) PDZdomaincontainingRINGfinger3 colagentriplehelixrepeatcontaining1 myosinregulatorylightchaininteractingprotein Sodiumchanel,voltage-gated,typeVI,alpha histonedeacetylase9 inhibitorofdnabinding2 myosin,heavypolypeptide10,non-muscle transmembraneprotein46 integrin,beta6 ATPase,(Na+)/K+transporting,beta4polypeptide ATPase,Ca+transporting,type2C,member1 meningiomaexpresedantigen6(coiled-coil proline-rich) phosphoinositide-3-kinase,clas2,betapolypeptide chemokine(c-x3-cmotif)receptor1 ubiquitinspecificprotease9,y-linked(fatfacets-like,drosophila) Ribosomal proteins23 ligand-dependentcorepresor mitogen-activatedproteinkinaseasociatedprotein1 aminomethyltransferase(glycinecleavagesystemproteint) membranemetalo-endopeptidase,cd10 Ankyrin3,nodeofRanvier(ankyrinG) glucocorticoidinducedtranscript1 phosphataseandactinregulator2 dual-specificitytyrosine-(y)-phosphorylationregulatedkinase2 mitogen-activatedproteinkinase9 tripartitemotif-containing45 TAF9-likeRNApolymeraseI zincfingerprotein252 LanClantibioticsynthetasecomponentC-like1(bacterial) alcohol dehydrogenaseib(clasi),betapolypeptide catenin(cadherin-asociatedprotein),delta1 fucosidase,alpha-l-1,tisue Rasasociation(RalGDS/AF-6)domainfamily4 basichelix-lop-helixdomaincontaining,clasb,3 nucleareceptorsubfamily1,groupd,member2 periodhomolog3(drosophila) vacuolarproteinsorting45a(yeast) unc-13homologb(c.elegans) nuclearfactornf-kapa-binhibitorkinase inter-alpha(globulin)inhibitorh4(plasmakalikrein-sensitiveglycoprotein) neural precursorcel expresed,developmentalydown-regulated1 Restin sonofsevenleshomolog2(drosophila) 2,3-bisphosphoglyceratemutase malicenzyme2,nad(+)-dependent,mitochondrial mesenchymal stemcel proteindsc54 tumorproteind52 uridine-cytidinekinase1-like1 secernin3 tripartitemotif-containing7 aquaporin4 dermatopontin putativelymphocyteg0/g1switchgene NuclearfactorI/B SETbindingprotein1 SERTAdomaincontaining2 transducin-likenhancerofsplit1 disheveledasociatedactivatorofmorphogenesis1 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase1 advilin GRB2-asociatedbindingprotein1 RhoGTPaseactivatingprotein18 adenylatecyclase2(brain) mucosasociatedlymphoidtisuelymphomatranslocationgene1 RAD51homologC(S.cerevisiae) CD38antigen(p45) Zincfinger,CHCdomaincontaining1 downregulatedinovariancancer1 pleckstrinhomologydomaininteractingprotein ankyrinrepeatandfyvedomaincontaining1 Endomucin Kelch-like1(Drosophila) inhibitorofdnabinding3 guanylatebindingprotein1,interferon-inducible,67kda v-ki-ras2kirstenratsarcomaviral oncogenehomolog fibronectinleucinerichtransmembraneprotein3 myeloidceleukemiasequence1(bcl2-related) Ubiquitin-conjugatingenzymeE2H(UBC8homolog,yeast) Rho-relatedBTBdomaincontaining1 inhibitorofdnabinding1 majorhistocompatibilitycomplex,clasi,dmalpha CD36antigen(colagentypeIreceptor,thrombospondinreceptor) Muscleblind-like(Drosophila) Sestrin1 DEAD(Asp-Glu-Ala-Asp)boxpolypeptide17 Partial mrnafort-cel receptorbetachain metalothionein1x adenosinemonophosphatedeaminase(isoforme) Catalase gangliosideinducediferentiationasociatedprotein2 Ependyminrelatedprotein1(zebrafish) RNAbindingmotifprotein6 imunoglobulinsuperfamily,member4 Proteinphosphatase1A,magnesium-dependent,alphaisoform Discs,largehomolog5(Drosophila) aryl hydrocarbonreceptornucleartranslocator-like splicingfactor1 Aryl hydrocarbonreceptornucleartranslocator insulin-likegrowthfactor1receptor familywithsequencesimilarity13,membera1 PogotransposablelementwithZNFdomain Abhydrolasedomaincontaining3 thioredoxininteractingprotein Ribosomal proteinl37a cytochromecoxidasesubunitviapolypeptide1 Wilmstumor1asociatedprotein Zincfingerprotein297B Fem-1homologa(C.elegans) Ribosomal proteins10 Iron-responsivelementbindingprotein2 Ribosomal proteinl27 ubiquitin-conjugatingenzymee2b(rad6homolog) HBxAgtransactivatedprotein2 ATPase,H+transporting,lysosomal 9kDa,V0subunite lungcancermetastasis-relatedprotein1 ribosomal proteinl38 Insulinreceptor CR4-NOTtranscriptioncomplex,subunit6-like Aminopeptidasepuromycinsensitive CytochromecoxidasesubunitVb Ribosomal proteins20 SourceofimunodominantMHC-asociatedpeptides Cysteine-richmotorneuron1 heatshock70kdaprotein1b zincfingerprotein403 Malatedehydrogenase1,NAD(soluble) FK506bindingprotein5 disheveledasociatedactivatorofmorphogenesis2 hexokinase2 trophoblast-derivednoncodingrna solutecarierfamily16(monocarboxylicacidtransporters),member7 Phosphodiesterase4D,cAMP-specific pyruvatedehydrogenasekinase,isoenzyme4 T-cel activationproteinphosphatase2c solutecarierfamily25,member5 estrogen-relatedreceptorgama Spermidine/spermineN1-acetyltransferase abhydrolasedomaincontaining2 translocaseofinermitochondrial membrane8homologa(yeast) muscledisease-relatedprotein fem-1homologb(c.elegans) proteintyrosinephosphatasedomaincontaining1 MethionineadenosyltransferaseI,alpha zincfingerprotein kDFMRPInteractingProtein histonedeacetylase4 nucleareceptorinteractingprotein1 kelchrepeatandbtb(poz)domaincontaining9 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 MAD2L1bindingprotein dysferlininteractingprotein1(tonin) signal-inducedproliferation-asociated1like3 Cholinephosphotransferase1 tumornecrosisfactoreceptorsuperfamily,member1a zincfingerprotein4(kox7) GTF2Irepeatdomaincontaining1 zincfingerprotein564 humanimunodeficiencyvirustypeienhancerbindingprotein2 pituitarytumor-transforming1interactingprotein myosin,heavypolypeptide9,non-muscle campresponsivelementmodulator solutecarierfamily19(thiaminetransporter),member2 aquaporin3 mitochondrial carierprotein ZincfingerandBTBdomaincontaining10 cryptochrome1(photolyase-like) lowdensitylipoproteinreceptor-relatedproteinbindingprotein UDP-glucoseceramideglucosyltransferase asparagine-linkedglycosylation2homolog TGFBinduciblearlygrowthresponse2 DnaJ(Hsp40)homolog,subfamilyB,member6 transcriptionfactor8(represesinterleukin2expresion) vestigialike2(drosophila) TGFBinduciblearlygrowthresponse Ras-relatedGTPbindingC LATS,largetumorsupresor,homolog2(Drosophila) nucleosomeasemblyprotein1-like5 moesin chlorideintracelularchanel 4 TGFB-inducedfactor(TALEfamilyhomeobox) actin,beta anexina3 insulinreceptorsubstrate2 tisueinhibitorofmetaloproteinase3 cofactorequiredforsp1transcriptional activation,subunit7,70kda coronin,actinbindingprotein,1c TBC1domainfamily,member14 chemokineorphanreceptor1 retinoblastomabindingprotein6 Transientreceptorpotential cationchanel,subfamilym,member7 tryptophanyl-trnasynthetase Jumonji,ATrichinteractivedomain2 thrombospondin1 microtubuleasociatedmonoxygenase,calponinandlim2 zincfingerprotein31 solutecarierfamily1(proton-coupledivalentmetal iontransporters),member2 hairy/enhancer-of-splitrelatedwithyrpwmotif1 ATPase,Na+/K+transporting,beta3polypeptide RAB20,memberRASoncogenefamily v-mafmusculoaponeuroticfibrosarcomaoncogenehomologf(avian) breastcanceranti-estrogenresistance3 TEKtyrosinekinase,endothelial tropomyosin4 FOS-likeantigen2 phosphatidylinositol transferprotein,cytoplasmic1 cytoplasmicpolyadenylationelementbindingprotein4 selenophosphatesynthetase2 vascularendothelial growthfactor peripheral myelinprotein2 v-mafmusculoaponeuroticfibrosarcomaoncogenehomologk(avian) fourandahalflimdomains2 sphingomyelinphosphodiesterase,acid-like3a angiopoietin-like4 Myelinbasicprotein Bcel RAGasociatedprotein nuclearfactor,interleukin3regulated nucleareceptorsubfamily4,groupa,member3 tumorproteinp73-like GABA(A)receptor-asociatedproteinlike1 Supresorofcytokinesignaling7 CHMP1.5protein interleukin6receptor angiopoietin-like2 pim-3oncogene salt-inducibleserine/threoninekinase2 v-etserythroblastosisviruse26oncogenehomolog2(avian) Sexcombonmidleg-like1(Drosophila) stomatin RAR-relatedorphanreceptorC MAXgeneasociated interleukin1receptor,typei peroxisomeproliferativeactivatedreceptor,gama,coactivator1,alpha forkheadboxo1a(rhabdomyosarcoma) Guaninenucleotidebindingprotein(Gprotein),alpha13 interferon,gama-inducibleprotein16 colagen,typeiv,alpha1 solutecarierfamily2(organicationtransporter),member5 SH3-domainbindingprotein5(BTK-asociated) TBC1domainfamily,member8(withGRAMdomain) potasiumvoltage-gatedchanel,kqt-likesubfamily,member4 ZincfingerandBTBdomaincontaining16 RNA,U2smal nucleolar Epidermal growthfactoreceptorpathwaysubstrate15-like1 pericentrin2(kendrin) basichelix-lop-helixdomaincontaining,clasb,2 mitogen-activatedproteinkinasekinasekinase2 hairy/enhancer-of-splitrelatedwithyrpwmotif2 phospholipidscramblase1 glucosamine-6-phosphatedeaminase1 Ubiquitinspecificprotease36 endothelial diferentiation,sphingolipidg-protein-coupledreceptor,3 synaptojanin2 esterase31 platelet/endothelial cel adhesionmolecule(cd31antigen) adrenomedulin Bicaudal Dhomolog1(Drosophila) Proteinkinase,AMP-activated,gama2non-catalyticsubunit Proteinkinase,cGMP-dependent,typeI Spectrin,beta,erythrocytic(includespherocytosis,clinical typei) Proteinphosphatase1,regulatory(inhibitor)subunit12B forkheadboxo3a frizledhomolog7(drosophila) eukaryotictranslationinitiationfactor2-alphakinase3 jundproto-oncogene SERTAdomaincontaining1 SorbinandSH3domaincontaining1 zyxin actin,gama1 integrin,alpha5(fibronectinreceptor,alphapolypeptide) Epidermal growthfactoreceptor fourandahalflimdomains5 periodhomolog2(drosophila) periodhomolog1(drosophila) Fms-relatedtyrosinekinase1(vegf/vpfreceptor) Nucleareceptorsubfamily3,groupC,member1(glucocorticoidreceptor) Isopentenyl-diphosphatedeltaisomerase arestindomaincontaining4 plexina2 dual specificityphosphatase1 Zincfingerprotein146 solutecarierfamily20(phosphatetransporter),member1 tumornecrosisfactoreceptorsuperfamily,member10b metastasisasociatedlungadenocarcinomatranscript1 smal proteinefector1ofcdc42 GTPbindingproteinoverexpresedinskeletal muscle Zincfingersandhomeoboxes2 brainandreproductiveorgan-expresed(tnfrsf1amodulator) spectrinrepeatcontaining,nuclearenvelope1 prostaglandinereceptor4(subtypeep4) FERMdomaincontaining4A glycoproteinarepetitionspredominant conectivetisuegrowthfactor karyopherinalpha2(ragcohort1,importinalpha1) RNAbindingproteinwithmultiplesplicing solutecarierfamily25(mitochondrial carier;phosphatecarier),member25 PQloprepeatcontaining1 proteinphosphatase2,regulatorysubunita(pr65),betaisoform SERPINH1/Heatshockprotein47 zincfingerprotein295 epithelial membraneprotein1 LIMandSH3protein1 p14356 mrna Transforming,acidicoiled-coil containingprotein2 Ankyrin1,erythrocytic imediatearlyresponse2 chemokine(c-x3-cmotif)ligand1 phosphodiesterase7a Familywithsequencesimilarity36,memberA golgi autoantigen,golginsubfamilya,4 Krupel-likefactor2(lung) V-raf-1murineleukemiaviral oncogenehomolog1 earlygrowthresponse3 Krupel-likefactor4(gut) serine/threoninekinase38like neural precursorcel expresed,developmentalydown-regulated9 Semaphorin4C Ankylosis,progresivehomolog(mouse) Rasinteractingprotein1 Ras-likewithoutCAX1 lowdensitylipoproteinreceptor(familial hypercholesterolemia) ATPase,ClasI,type8B,member1 Elongationfactor,RNApolymeraseI,2 plasminogenactivator,urokinase testisderivedtranscript(3limdomains) proteinphosphatase1dmagnesium-dependent,deltaisoform nucleosidephosphorylase AXIN1up-regulated1 regulatorofg-proteinsignaling2,24kda KITligand STARTdomaincontaining4,sterol regulated Mortalityfactor4like2 solutecarierfamily2(facilitatedglucosetransporter),member3 Sirtuin(silentmatingtypeinformationregulation2homolog)2(S.cerevisiae) BTGfamily,member3 chemokine(c-cmotif)ligand8 Staniocalcin1 nucleareceptorsubfamily4,groupa,member2 ADAMTS9metaloprotease GTPcyclohydrolase1(dopa-responsivedystonia) FilaminB,beta(actinbindingprotein278) PCTAIREproteinkinase2 Musashi homolog2(drosophila) phorbol-12-myristate-13-acetate-inducedprotein1 Nexin,plasminogenactivatorinhibitortype1 deletedinlivercancer1 SimilartoD(1B)dopaminereceptor Actinin,alpha4 ADAMTS1metaloprotease Microtubule-asociatedprotein,RP/EBfamily,member2 MAXdimerizationprotein1 cysteine-rich,angiogenicinducer,61 proteinphosphatase1,regulatory(inhibitor)subunit15a chemokine(c-x-cmotif)ligand2 pleckstrinhomologydomaincontaining,familygmember1 heatshock105kda/10kdaprotein1 lysozyme(renal amyloidosis) mesenchymehomeobox1 ubiquitinspecificprotease2 myeloid/lymphoidormixed-lineageleukemia TPRdomain,ankyrin-repeatandcoiled-coil-containing programedcel death1ligand1 ChromodomainhelicaseDNAbindingprotein1 caldesmon1 ringfingerprotein138 RING1andY1bindingprotein CUGtripletrepeat,RNAbindingprotein2 tyrosine3-monoxygenase/tryptophan5-monoxygenaseactivationprotein,eta dynein,cytoplasmic,lightpolypeptide1 phosphatidylinositol bindingclathrinasemblyprotein tightjunctionprotein2(zonaocludens2) tribleshomolog1(drosophila) chlorideintracelularchanel 1 striatedmuscleactivatorofrho-dependentsignaling alpha-kinase3 DnaJ(Hsp40)homolog,subfamilyA,member1 mitogen-induciblegene6 zincfingerprotein36,c3htype-like1 Ankyrinrepeatdomain9 zincfinger,chcdomaincontaining2 cysteineandglycine-richprotein1 Akinase(PRKA)anchorprotein(gravin)12 zincfingerprotein36 nestin epithelial V-likeantigen1 endoglin(osler-rendu-webersyndrome1) N-mycdownstreamregulatedgene1 tubulin,beta2 discoidin,cubandlcldomaincontaining1 LIMprotein(similartoratproteinkinaseC-bindingenigma) ELOVLfamilymember5,elongationoflongchainfatyacids adrenergic,beta-2-,receptor,surface myeloid-asociatediferentiationmarker syntaxin12 ATrichinteractivedomain5B(MRF1-like) interferon-relatedevelopmental regulator1 tubulin,beta6 proteinphosphatase1,regulatory(inhibitor)subunit3e tubulin,alpha3 chemokine(c-cmotif)ligand2 Chr2synaptotagmin actin,alpha2,smothmuscle,aorta CAP,adenylatecyclase-asociatedprotein1(yeast) 0 3h 6h 9h 24h Up-regulation Down-regulation

161 Ex-0 Ex-3 Ex-6 Ex-9 Ex fatyacidbindingprotein3,muscleandheart tumorsupresordeletedinoral cancer-related1 heatshockprotein,alpha-crystalin-related,b6 carboxylesterase2(intestine,liver) glutaredoxin(thioltransferase) al-trans-13,14-dihydroretinol saturase cholinergicreceptor,nicotinic,alphapolypeptide1(muscle) purinergicreceptorp2x,ligand-gatedionchanel,5 colagen-liketail subunitofasymetricacetylcholinesterase angiomotinlike1 signal-inducedproliferation-asociated1like2 isocitratedehydrogenase3(nad+)alpha solutecarierfamily25(carnitine/acylcarnitinetranslocase),member20 mitochondrial protein18kda myosinbindingproteinh humanimuneasociatednucleotide6 Zincfingerprotein302 DNA-damage-inducibletranscript4-like Plasminogen-like growthdiferentiationfactor8 eukaryotictranslationinitiationfactor4a,isoform2 Thyroidhormonereceptorasociatedprotein1 Dystrobrevin,alpha Titinimunoglobulindomainprotein(myotilin) Semaphorin6D carbonicanhydraseiv regucalcingenepromotoregionrelatedprotein Dsiteofalbuminpromoter(albuminD-box)bindingprotein nuclearfactornf-kapa-binhibitoralpha Neuroserpin LIMdomainbinding2 thyroidhormonereceptor,alpha DAPK-interactingprotein1 Zincfinger,MYNDdomaincontaining17 synaptotagmin-like3 ankyrinrepeatdomain20a flavincontainingmonoxygenase2 CXCfinger6 Phosphonoformateimuno-asociatedprotein5 RAR-relatedorphanreceptorA dual specificityphosphatase10 Myocytenhancerfactor2C myosinx syntaxinbindingprotein6(amisyn) WDrepeatandSOCSbox-containing1 ectonucleotidepyrophosphatase/phosphodiesterase2(autotaxin) PDZdomaincontainingRINGfinger3 colagentriplehelixrepeatcontaining1 myosinregulatorylightchaininteractingprotein Sodiumchanel,voltage-gated,typeVI,alpha histonedeacetylase9 inhibitorofdnabinding2 myosin,heavypolypeptide10,non-muscle transmembraneprotein46 integrin,beta6 ATPase,(Na+)/K+transporting,beta4polypeptide ATPase,Ca+transporting,type2C,member1 meningiomaexpresedantigen6(coiled-coil proline-rich) phosphoinositide-3-kinase,clas2,betapolypeptide chemokine(c-x3-cmotif)receptor1 ubiquitinspecificprotease9,y-linked(fatfacets-like,drosophila) Ribosomal proteins23 ligand-dependentcorepresor mitogen-activatedproteinkinaseasociatedprotein1 aminomethyltransferase(glycinecleavagesystemproteint) membranemetalo-endopeptidase,cd10 Ankyrin3,nodeofRanvier(ankyrinG) glucocorticoidinducedtranscript1 phosphataseandactinregulator2 dual-specificitytyrosine-(y)-phosphorylationregulatedkinase2 mitogen-activatedproteinkinase9 tripartitemotif-containing45 TAF9-likeRNApolymeraseI zincfingerprotein252 LanClantibioticsynthetasecomponentC-like1(bacterial) alcohol dehydrogenaseib(clasi),betapolypeptide catenin(cadherin-asociatedprotein),delta1 fucosidase,alpha-l-1,tisue Rasasociation(RalGDS/AF-6)domainfamily4 basichelix-lop-helixdomaincontaining,clasb,3 nucleareceptorsubfamily1,groupd,member2 periodhomolog3(drosophila) vacuolarproteinsorting45a(yeast) unc-13homologb(c.elegans) nuclearfactornf-kapa-binhibitorkinase inter-alpha(globulin)inhibitorh4(plasmakalikrein-sensitiveglycoprotein) neural precursorcel expresed,developmentalydown-regulated1 Restin sonofsevenleshomolog2(drosophila) 2,3-bisphosphoglyceratemutase malicenzyme2,nad(+)-dependent,mitochondrial mesenchymal stemcel proteindsc54 tumorproteind52 uridine-cytidinekinase1-like1 secernin3 tripartitemotif-containing7 aquaporin4 dermatopontin putativelymphocyteg0/g1switchgene NuclearfactorI/B SETbindingprotein1 SERTAdomaincontaining2 transducin-likenhancerofsplit1 disheveledasociatedactivatorofmorphogenesis1 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase1 advilin GRB2-asociatedbindingprotein1 RhoGTPaseactivatingprotein18 adenylatecyclase2(brain) mucosasociatedlymphoidtisuelymphomatranslocationgene1 RAD51homologC(S.cerevisiae) CD38antigen(p45) Zincfinger,CHCdomaincontaining1 downregulatedinovariancancer1 pleckstrinhomologydomaininteractingprotein ankyrinrepeatandfyvedomaincontaining1 Endomucin Kelch-like1(Drosophila) inhibitorofdnabinding3 guanylatebindingprotein1,interferon-inducible,67kda v-ki-ras2kirstenratsarcomaviral oncogenehomolog fibronectinleucinerichtransmembraneprotein3 myeloidceleukemiasequence1(bcl2-related) Ubiquitin-conjugatingenzymeE2H(UBC8homolog,yeast) Rho-relatedBTBdomaincontaining1 inhibitorofdnabinding1 majorhistocompatibilitycomplex,clasi,dmalpha CD36antigen(colagentypeIreceptor,thrombospondinreceptor) Muscleblind-like(Drosophila) Sestrin1 DEAD(Asp-Glu-Ala-Asp)boxpolypeptide17 Partial mrnafort-cel receptorbetachain metalothionein1x adenosinemonophosphatedeaminase(isoforme) Catalase gangliosideinducediferentiationasociatedprotein2 Ependyminrelatedprotein1(zebrafish) RNAbindingmotifprotein6 imunoglobulinsuperfamily,member4 Proteinphosphatase1A,magnesium-dependent,alphaisoform Discs,largehomolog5(Drosophila) aryl hydrocarbonreceptornucleartranslocator-like splicingfactor1 Aryl hydrocarbonreceptornucleartranslocator insulin-likegrowthfactor1receptor familywithsequencesimilarity13,membera1 PogotransposablelementwithZNFdomain Abhydrolasedomaincontaining3 thioredoxininteractingprotein Ribosomal proteinl37a cytochromecoxidasesubunitviapolypeptide1 Wilmstumor1asociatedprotein Zincfingerprotein297B Fem-1homologa(C.elegans) Ribosomal proteins10 Iron-responsivelementbindingprotein2 Ribosomal proteinl27 ubiquitin-conjugatingenzymee2b(rad6homolog) HBxAgtransactivatedprotein2 ATPase,H+transporting,lysosomal 9kDa,V0subunite lungcancermetastasis-relatedprotein1 ribosomal proteinl38 Insulinreceptor CR4-NOTtranscriptioncomplex,subunit6-like Aminopeptidasepuromycinsensitive CytochromecoxidasesubunitVb Ribosomal proteins20 SourceofimunodominantMHC-asociatedpeptides Cysteine-richmotorneuron1 heatshock70kdaprotein1b zincfingerprotein403 Malatedehydrogenase1,NAD(soluble) FK506bindingprotein5 disheveledasociatedactivatorofmorphogenesis2 hexokinase2 trophoblast-derivednoncodingrna solutecarierfamily16(monocarboxylicacidtransporters),member7 Phosphodiesterase4D,cAMP-specific pyruvatedehydrogenasekinase,isoenzyme4 T-cel activationproteinphosphatase2c solutecarierfamily25,member5 estrogen-relatedreceptorgama Spermidine/spermineN1-acetyltransferase abhydrolasedomaincontaining2 translocaseofinermitochondrial membrane8homologa(yeast) muscledisease-relatedprotein fem-1homologb(c.elegans) proteintyrosinephosphatasedomaincontaining1 MethionineadenosyltransferaseI,alpha zincfingerprotein kDFMRPInteractingProtein histonedeacetylase4 nucleareceptorinteractingprotein1 kelchrepeatandbtb(poz)domaincontaining9 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 MAD2L1bindingprotein dysferlininteractingprotein1(tonin) signal-inducedproliferation-asociated1like3 Cholinephosphotransferase1 tumornecrosisfactoreceptorsuperfamily,member1a zincfingerprotein4(kox7) GTF2Irepeatdomaincontaining1 zincfingerprotein564 humanimunodeficiencyvirustypeienhancerbindingprotein2 pituitarytumor-transforming1interactingprotein myosin,heavypolypeptide9,non-muscle campresponsivelementmodulator solutecarierfamily19(thiaminetransporter),member2 aquaporin3 mitochondrial carierprotein ZincfingerandBTBdomaincontaining10 cryptochrome1(photolyase-like) lowdensitylipoproteinreceptor-relatedproteinbindingprotein UDP-glucoseceramideglucosyltransferase asparagine-linkedglycosylation2homolog TGFBinduciblearlygrowthresponse2 DnaJ(Hsp40)homolog,subfamilyB,member6 transcriptionfactor8(represesinterleukin2expresion) vestigialike2(drosophila) TGFBinduciblearlygrowthresponse Ras-relatedGTPbindingC LATS,largetumorsupresor,homolog2(Drosophila) nucleosomeasemblyprotein1-like5 moesin chlorideintracelularchanel 4 TGFB-inducedfactor(TALEfamilyhomeobox) actin,beta anexina3 insulinreceptorsubstrate2 tisueinhibitorofmetaloproteinase3 cofactorequiredforsp1transcriptional activation,subunit7,70kda coronin,actinbindingprotein,1c TBC1domainfamily,member14 chemokineorphanreceptor1 retinoblastomabindingprotein6 Transientreceptorpotential cationchanel,subfamilym,member7 tryptophanyl-trnasynthetase Jumonji,ATrichinteractivedomain2 thrombospondin1 microtubuleasociatedmonoxygenase,calponinandlim2 zincfingerprotein31 solutecarierfamily1(proton-coupledivalentmetal iontransporters),member2 hairy/enhancer-of-splitrelatedwithyrpwmotif1 ATPase,Na+/K+transporting,beta3polypeptide RAB20,memberRASoncogenefamily v-mafmusculoaponeuroticfibrosarcomaoncogenehomologf(avian) breastcanceranti-estrogenresistance3 TEKtyrosinekinase,endothelial tropomyosin4 FOS-likeantigen2 phosphatidylinositol transferprotein,cytoplasmic1 cytoplasmicpolyadenylationelementbindingprotein4 selenophosphatesynthetase2 vascularendothelial growthfactor peripheral myelinprotein2 v-mafmusculoaponeuroticfibrosarcomaoncogenehomologk(avian) fourandahalflimdomains2 sphingomyelinphosphodiesterase,acid-like3a angiopoietin-like4 Myelinbasicprotein Bcel RAGasociatedprotein nuclearfactor,interleukin3regulated nucleareceptorsubfamily4,groupa,member3 tumorproteinp73-like GABA(A)receptor-asociatedproteinlike1 Supresorofcytokinesignaling7 CHMP1.5protein interleukin6receptor angiopoietin-like2 pim-3oncogene salt-inducibleserine/threoninekinase2 v-etserythroblastosisviruse26oncogenehomolog2(avian) Sexcombonmidleg-like1(Drosophila) stomatin RAR-relatedorphanreceptorC MAXgeneasociated interleukin1receptor,typei peroxisomeproliferativeactivatedreceptor,gama,coactivator1,alpha forkheadboxo1a(rhabdomyosarcoma) Guaninenucleotidebindingprotein(Gprotein),alpha13 interferon,gama-inducibleprotein16 colagen,typeiv,alpha1 solutecarierfamily2(organicationtransporter),member5 SH3-domainbindingprotein5(BTK-asociated) TBC1domainfamily,member8(withGRAMdomain) potasiumvoltage-gatedchanel,kqt-likesubfamily,member4 ZincfingerandBTBdomaincontaining16 RNA,U2smal nucleolar Epidermal growthfactoreceptorpathwaysubstrate15-like1 pericentrin2(kendrin) basichelix-lop-helixdomaincontaining,clasb,2 mitogen-activatedproteinkinasekinasekinase2 hairy/enhancer-of-splitrelatedwithyrpwmotif2 phospholipidscramblase1 glucosamine-6-phosphatedeaminase1 Ubiquitinspecificprotease36 endothelial diferentiation,sphingolipidg-protein-coupledreceptor,3 synaptojanin2 esterase31 platelet/endothelial cel adhesionmolecule(cd31antigen) adrenomedulin Bicaudal Dhomolog1(Drosophila) Proteinkinase,AMP-activated,gama2non-catalyticsubunit Proteinkinase,cGMP-dependent,typeI Spectrin,beta,erythrocytic(includespherocytosis,clinical typei) Proteinphosphatase1,regulatory(inhibitor)subunit12B forkheadboxo3a frizledhomolog7(drosophila) eukaryotictranslationinitiationfactor2-alphakinase3 jundproto-oncogene SERTAdomaincontaining1 SorbinandSH3domaincontaining1 zyxin actin,gama1 integrin,alpha5(fibronectinreceptor,alphapolypeptide) Epidermal growthfactoreceptor fourandahalflimdomains5 periodhomolog2(drosophila) periodhomolog1(drosophila) Fms-relatedtyrosinekinase1(vegf/vpfreceptor) Nucleareceptorsubfamily3,groupC,member1(glucocorticoidreceptor) Isopentenyl-diphosphatedeltaisomerase arestindomaincontaining4 plexina2 dual specificityphosphatase1 Zincfingerprotein146 solutecarierfamily20(phosphatetransporter),member1 tumornecrosisfactoreceptorsuperfamily,member10b metastasisasociatedlungadenocarcinomatranscript1 smal proteinefector1ofcdc42 GTPbindingproteinoverexpresedinskeletal muscle Zincfingersandhomeoboxes2 brainandreproductiveorgan-expresed(tnfrsf1amodulator) spectrinrepeatcontaining,nuclearenvelope1 prostaglandinereceptor4(subtypeep4) FERMdomaincontaining4A glycoproteinarepetitionspredominant conectivetisuegrowthfactor karyopherinalpha2(ragcohort1,importinalpha1) RNAbindingproteinwithmultiplesplicing solutecarierfamily25(mitochondrial carier;phosphatecarier),member25 PQloprepeatcontaining1 proteinphosphatase2,regulatorysubunita(pr65),betaisoform SERPINH1/Heatshockprotein47 zincfingerprotein295 epithelial membraneprotein1 LIMandSH3protein1 p14356 mrna Transforming,acidicoiled-coil containingprotein2 Ankyrin1,erythrocytic imediatearlyresponse2 chemokine(c-x3-cmotif)ligand1 phosphodiesterase7a Familywithsequencesimilarity36,memberA golgi autoantigen,golginsubfamilya,4 Krupel-likefactor2(lung) V-raf-1murineleukemiaviral oncogenehomolog1 earlygrowthresponse3 Krupel-likefactor4(gut) serine/threoninekinase38like neural precursorcel expresed,developmentalydown-regulated9 Semaphorin4C Ankylosis,progresivehomolog(mouse) Rasinteractingprotein1 Ras-likewithoutCAX1 lowdensitylipoproteinreceptor(familial hypercholesterolemia) ATPase,ClasI,type8B,member1 Elongationfactor,RNApolymeraseI,2 plasminogenactivator,urokinase testisderivedtranscript(3limdomains) proteinphosphatase1dmagnesium-dependent,deltaisoform nucleosidephosphorylase AXIN1up-regulated1 regulatorofg-proteinsignaling2,24kda KITligand STARTdomaincontaining4,sterol regulated Mortalityfactor4like2 solutecarierfamily2(facilitatedglucosetransporter),member3 Sirtuin(silentmatingtypeinformationregulation2homolog)2(S.cerevisiae) BTGfamily,member3 chemokine(c-cmotif)ligand8 Staniocalcin1 nucleareceptorsubfamily4,groupa,member2 ADAMTS9metaloprotease GTPcyclohydrolase1(dopa-responsivedystonia) FilaminB,beta(actinbindingprotein278) PCTAIREproteinkinase2 Musashi homolog2(drosophila) phorbol-12-myristate-13-acetate-inducedprotein1 Nexin,plasminogenactivatorinhibitortype1 deletedinlivercancer1 SimilartoD(1B)dopaminereceptor Actinin,alpha4 ADAMTS1metaloprotease Microtubule-asociatedprotein,RP/EBfamily,member2 MAXdimerizationprotein1 cysteine-rich,angiogenicinducer,61 proteinphosphatase1,regulatory(inhibitor)subunit15a chemokine(c-x-cmotif)ligand2 pleckstrinhomologydomaincontaining,familygmember1 heatshock105kda/10kdaprotein1 lysozyme(renal amyloidosis) mesenchymehomeobox1 ubiquitinspecificprotease2 myeloid/lymphoidormixed-lineageleukemia TPRdomain,ankyrin-repeatandcoiled-coil-containing programedcel death1ligand1 ChromodomainhelicaseDNAbindingprotein1 caldesmon1 ringfingerprotein138 RING1andY1bindingprotein CUGtripletrepeat,RNAbindingprotein2 tyrosine3-monoxygenase/tryptophan5-monoxygenaseactivationprotein,eta dynein,cytoplasmic,lightpolypeptide1 phosphatidylinositol bindingclathrinasemblyprotein tightjunctionprotein2(zonaocludens2) tribleshomolog1(drosophila) chlorideintracelularchanel 1 striatedmuscleactivatorofrho-dependentsignaling alpha-kinase3 DnaJ(Hsp40)homolog,subfamilyA,member1 mitogen-induciblegene6 zincfingerprotein36,c3htype-like1 Ankyrinrepeatdomain9 zincfinger,chcdomaincontaining2 cysteineandglycine-richprotein1 Akinase(PRKA)anchorprotein(gravin)12 zincfingerprotein36 nestin epithelial V-likeantigen1 endoglin(osler-rendu-webersyndrome1) N-mycdownstreamregulatedgene1 tubulin,beta2 discoidin,cubandlcldomaincontaining1 LIMprotein(similartoratproteinkinaseC-bindingenigma) ELOVLfamilymember5,elongationoflongchainfatyacids adrenergic,beta-2-,receptor,surface myeloid-asociatediferentiationmarker syntaxin12 ATrichinteractivedomain5B(MRF1-like) interferon-relatedevelopmental regulator1 tubulin,beta6 proteinphosphatase1,regulatory(inhibitor)subunit3e tubulin,alpha3 chemokine(c-cmotif)ligand2 Chr2synaptotagmin actin,alpha2,smothmuscle,aorta CAP,adenylatecyclase-asociatedprotein1(yeast) Exercise-induced transient gene responses mrna content Exercise Stress responsive genes 1-2 h recovery 24 h recovery Time

162 Ex-0 Ex-3 Ex-6 Ex-9 Ex fatyacidbindingprotein3,muscleandheart tumorsupresordeletedinoral cancer-related1 heatshockprotein,alpha-crystalin-related,b6 carboxylesterase2(intestine,liver) glutaredoxin(thioltransferase) al-trans-13,14-dihydroretinol saturase cholinergicreceptor,nicotinic,alphapolypeptide1(muscle) purinergicreceptorp2x,ligand-gatedionchanel,5 colagen-liketail subunitofasymetricacetylcholinesterase angiomotinlike1 signal-inducedproliferation-asociated1like2 isocitratedehydrogenase3(nad+)alpha solutecarierfamily25(carnitine/acylcarnitinetranslocase),member20 mitochondrial protein18kda myosinbindingproteinh humanimuneasociatednucleotide6 Zincfingerprotein302 DNA-damage-inducibletranscript4-like Plasminogen-like growthdiferentiationfactor8 eukaryotictranslationinitiationfactor4a,isoform2 Thyroidhormonereceptorasociatedprotein1 Dystrobrevin,alpha Titinimunoglobulindomainprotein(myotilin) Semaphorin6D carbonicanhydraseiv regucalcingenepromotoregionrelatedprotein Dsiteofalbuminpromoter(albuminD-box)bindingprotein nuclearfactornf-kapa-binhibitoralpha Neuroserpin LIMdomainbinding2 thyroidhormonereceptor,alpha DAPK-interactingprotein1 Zincfinger,MYNDdomaincontaining17 synaptotagmin-like3 ankyrinrepeatdomain20a flavincontainingmonoxygenase2 CXCfinger6 Phosphonoformateimuno-asociatedprotein5 RAR-relatedorphanreceptorA dual specificityphosphatase10 Myocytenhancerfactor2C myosinx syntaxinbindingprotein6(amisyn) WDrepeatandSOCSbox-containing1 ectonucleotidepyrophosphatase/phosphodiesterase2(autotaxin) PDZdomaincontainingRINGfinger3 colagentriplehelixrepeatcontaining1 myosinregulatorylightchaininteractingprotein Sodiumchanel,voltage-gated,typeVI,alpha histonedeacetylase9 inhibitorofdnabinding2 myosin,heavypolypeptide10,non-muscle transmembraneprotein46 integrin,beta6 ATPase,(Na+)/K+transporting,beta4polypeptide ATPase,Ca+transporting,type2C,member1 meningiomaexpresedantigen6(coiled-coil proline-rich) phosphoinositide-3-kinase,clas2,betapolypeptide chemokine(c-x3-cmotif)receptor1 ubiquitinspecificprotease9,y-linked(fatfacets-like,drosophila) Ribosomal proteins23 ligand-dependentcorepresor mitogen-activatedproteinkinaseasociatedprotein1 aminomethyltransferase(glycinecleavagesystemproteint) membranemetalo-endopeptidase,cd10 Ankyrin3,nodeofRanvier(ankyrinG) glucocorticoidinducedtranscript1 phosphataseandactinregulator2 dual-specificitytyrosine-(y)-phosphorylationregulatedkinase2 mitogen-activatedproteinkinase9 tripartitemotif-containing45 TAF9-likeRNApolymeraseI zincfingerprotein252 LanClantibioticsynthetasecomponentC-like1(bacterial) alcohol dehydrogenaseib(clasi),betapolypeptide catenin(cadherin-asociatedprotein),delta1 fucosidase,alpha-l-1,tisue Rasasociation(RalGDS/AF-6)domainfamily4 basichelix-lop-helixdomaincontaining,clasb,3 nucleareceptorsubfamily1,groupd,member2 periodhomolog3(drosophila) vacuolarproteinsorting45a(yeast) unc-13homologb(c.elegans) nuclearfactornf-kapa-binhibitorkinase inter-alpha(globulin)inhibitorh4(plasmakalikrein-sensitiveglycoprotein) neural precursorcel expresed,developmentalydown-regulated1 Restin sonofsevenleshomolog2(drosophila) 2,3-bisphosphoglyceratemutase malicenzyme2,nad(+)-dependent,mitochondrial mesenchymal stemcel proteindsc54 tumorproteind52 uridine-cytidinekinase1-like1 secernin3 tripartitemotif-containing7 aquaporin4 dermatopontin putativelymphocyteg0/g1switchgene NuclearfactorI/B SETbindingprotein1 SERTAdomaincontaining2 transducin-likenhancerofsplit1 disheveledasociatedactivatorofmorphogenesis1 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase1 advilin GRB2-asociatedbindingprotein1 RhoGTPaseactivatingprotein18 adenylatecyclase2(brain) mucosasociatedlymphoidtisuelymphomatranslocationgene1 RAD51homologC(S.cerevisiae) CD38antigen(p45) Zincfinger,CHCdomaincontaining1 downregulatedinovariancancer1 pleckstrinhomologydomaininteractingprotein ankyrinrepeatandfyvedomaincontaining1 Endomucin Kelch-like1(Drosophila) inhibitorofdnabinding3 guanylatebindingprotein1,interferon-inducible,67kda v-ki-ras2kirstenratsarcomaviral oncogenehomolog fibronectinleucinerichtransmembraneprotein3 myeloidceleukemiasequence1(bcl2-related) Ubiquitin-conjugatingenzymeE2H(UBC8homolog,yeast) Rho-relatedBTBdomaincontaining1 inhibitorofdnabinding1 majorhistocompatibilitycomplex,clasi,dmalpha CD36antigen(colagentypeIreceptor,thrombospondinreceptor) Muscleblind-like(Drosophila) Sestrin1 DEAD(Asp-Glu-Ala-Asp)boxpolypeptide17 Partial mrnafort-cel receptorbetachain metalothionein1x adenosinemonophosphatedeaminase(isoforme) Catalase gangliosideinducediferentiationasociatedprotein2 Ependyminrelatedprotein1(zebrafish) RNAbindingmotifprotein6 imunoglobulinsuperfamily,member4 Proteinphosphatase1A,magnesium-dependent,alphaisoform Discs,largehomolog5(Drosophila) aryl hydrocarbonreceptornucleartranslocator-like splicingfactor1 Aryl hydrocarbonreceptornucleartranslocator insulin-likegrowthfactor1receptor familywithsequencesimilarity13,membera1 PogotransposablelementwithZNFdomain Abhydrolasedomaincontaining3 thioredoxininteractingprotein Ribosomal proteinl37a cytochromecoxidasesubunitviapolypeptide1 Wilmstumor1asociatedprotein Zincfingerprotein297B Fem-1homologa(C.elegans) Ribosomal proteins10 Iron-responsivelementbindingprotein2 Ribosomal proteinl27 ubiquitin-conjugatingenzymee2b(rad6homolog) HBxAgtransactivatedprotein2 ATPase,H+transporting,lysosomal 9kDa,V0subunite lungcancermetastasis-relatedprotein1 ribosomal proteinl38 Insulinreceptor CR4-NOTtranscriptioncomplex,subunit6-like Aminopeptidasepuromycinsensitive CytochromecoxidasesubunitVb Ribosomal proteins20 SourceofimunodominantMHC-asociatedpeptides Cysteine-richmotorneuron1 heatshock70kdaprotein1b zincfingerprotein403 Malatedehydrogenase1,NAD(soluble) FK506bindingprotein5 disheveledasociatedactivatorofmorphogenesis2 hexokinase2 trophoblast-derivednoncodingrna solutecarierfamily16(monocarboxylicacidtransporters),member7 Phosphodiesterase4D,cAMP-specific pyruvatedehydrogenasekinase,isoenzyme4 T-cel activationproteinphosphatase2c solutecarierfamily25,member5 estrogen-relatedreceptorgama Spermidine/spermineN1-acetyltransferase abhydrolasedomaincontaining2 translocaseofinermitochondrial membrane8homologa(yeast) muscledisease-relatedprotein fem-1homologb(c.elegans) proteintyrosinephosphatasedomaincontaining1 MethionineadenosyltransferaseI,alpha zincfingerprotein kDFMRPInteractingProtein histonedeacetylase4 nucleareceptorinteractingprotein1 kelchrepeatandbtb(poz)domaincontaining9 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 MAD2L1bindingprotein dysferlininteractingprotein1(tonin) signal-inducedproliferation-asociated1like3 Cholinephosphotransferase1 tumornecrosisfactoreceptorsuperfamily,member1a zincfingerprotein4(kox7) GTF2Irepeatdomaincontaining1 zincfingerprotein564 humanimunodeficiencyvirustypeienhancerbindingprotein2 pituitarytumor-transforming1interactingprotein myosin,heavypolypeptide9,non-muscle campresponsivelementmodulator solutecarierfamily19(thiaminetransporter),member2 aquaporin3 mitochondrial carierprotein ZincfingerandBTBdomaincontaining10 cryptochrome1(photolyase-like) lowdensitylipoproteinreceptor-relatedproteinbindingprotein UDP-glucoseceramideglucosyltransferase asparagine-linkedglycosylation2homolog TGFBinduciblearlygrowthresponse2 DnaJ(Hsp40)homolog,subfamilyB,member6 transcriptionfactor8(represesinterleukin2expresion) vestigialike2(drosophila) TGFBinduciblearlygrowthresponse Ras-relatedGTPbindingC LATS,largetumorsupresor,homolog2(Drosophila) nucleosomeasemblyprotein1-like5 moesin chlorideintracelularchanel 4 TGFB-inducedfactor(TALEfamilyhomeobox) actin,beta anexina3 insulinreceptorsubstrate2 tisueinhibitorofmetaloproteinase3 cofactorequiredforsp1transcriptional activation,subunit7,70kda coronin,actinbindingprotein,1c TBC1domainfamily,member14 chemokineorphanreceptor1 retinoblastomabindingprotein6 Transientreceptorpotential cationchanel,subfamilym,member7 tryptophanyl-trnasynthetase Jumonji,ATrichinteractivedomain2 thrombospondin1 microtubuleasociatedmonoxygenase,calponinandlim2 zincfingerprotein31 solutecarierfamily1(proton-coupledivalentmetal iontransporters),member2 hairy/enhancer-of-splitrelatedwithyrpwmotif1 ATPase,Na+/K+transporting,beta3polypeptide RAB20,memberRASoncogenefamily v-mafmusculoaponeuroticfibrosarcomaoncogenehomologf(avian) breastcanceranti-estrogenresistance3 TEKtyrosinekinase,endothelial tropomyosin4 FOS-likeantigen2 phosphatidylinositol transferprotein,cytoplasmic1 cytoplasmicpolyadenylationelementbindingprotein4 selenophosphatesynthetase2 vascularendothelial growthfactor peripheral myelinprotein2 v-mafmusculoaponeuroticfibrosarcomaoncogenehomologk(avian) fourandahalflimdomains2 sphingomyelinphosphodiesterase,acid-like3a angiopoietin-like4 Myelinbasicprotein Bcel RAGasociatedprotein nuclearfactor,interleukin3regulated nucleareceptorsubfamily4,groupa,member3 tumorproteinp73-like GABA(A)receptor-asociatedproteinlike1 Supresorofcytokinesignaling7 CHMP1.5protein interleukin6receptor angiopoietin-like2 pim-3oncogene salt-inducibleserine/threoninekinase2 v-etserythroblastosisviruse26oncogenehomolog2(avian) Sexcombonmidleg-like1(Drosophila) stomatin RAR-relatedorphanreceptorC MAXgeneasociated interleukin1receptor,typei peroxisomeproliferativeactivatedreceptor,gama,coactivator1,alpha forkheadboxo1a(rhabdomyosarcoma) Guaninenucleotidebindingprotein(Gprotein),alpha13 interferon,gama-inducibleprotein16 colagen,typeiv,alpha1 solutecarierfamily2(organicationtransporter),member5 SH3-domainbindingprotein5(BTK-asociated) TBC1domainfamily,member8(withGRAMdomain) potasiumvoltage-gatedchanel,kqt-likesubfamily,member4 ZincfingerandBTBdomaincontaining16 RNA,U2smal nucleolar Epidermal growthfactoreceptorpathwaysubstrate15-like1 pericentrin2(kendrin) basichelix-lop-helixdomaincontaining,clasb,2 mitogen-activatedproteinkinasekinasekinase2 hairy/enhancer-of-splitrelatedwithyrpwmotif2 phospholipidscramblase1 glucosamine-6-phosphatedeaminase1 Ubiquitinspecificprotease36 endothelial diferentiation,sphingolipidg-protein-coupledreceptor,3 synaptojanin2 esterase31 platelet/endothelial cel adhesionmolecule(cd31antigen) adrenomedulin Bicaudal Dhomolog1(Drosophila) Proteinkinase,AMP-activated,gama2non-catalyticsubunit Proteinkinase,cGMP-dependent,typeI Spectrin,beta,erythrocytic(includespherocytosis,clinical typei) Proteinphosphatase1,regulatory(inhibitor)subunit12B forkheadboxo3a frizledhomolog7(drosophila) eukaryotictranslationinitiationfactor2-alphakinase3 jundproto-oncogene SERTAdomaincontaining1 SorbinandSH3domaincontaining1 zyxin actin,gama1 integrin,alpha5(fibronectinreceptor,alphapolypeptide) Epidermal growthfactoreceptor fourandahalflimdomains5 periodhomolog2(drosophila) periodhomolog1(drosophila) Fms-relatedtyrosinekinase1(vegf/vpfreceptor) Nucleareceptorsubfamily3,groupC,member1(glucocorticoidreceptor) Isopentenyl-diphosphatedeltaisomerase arestindomaincontaining4 plexina2 dual specificityphosphatase1 Zincfingerprotein146 solutecarierfamily20(phosphatetransporter),member1 tumornecrosisfactoreceptorsuperfamily,member10b metastasisasociatedlungadenocarcinomatranscript1 smal proteinefector1ofcdc42 GTPbindingproteinoverexpresedinskeletal muscle Zincfingersandhomeoboxes2 brainandreproductiveorgan-expresed(tnfrsf1amodulator) spectrinrepeatcontaining,nuclearenvelope1 prostaglandinereceptor4(subtypeep4) FERMdomaincontaining4A glycoproteinarepetitionspredominant conectivetisuegrowthfactor karyopherinalpha2(ragcohort1,importinalpha1) RNAbindingproteinwithmultiplesplicing solutecarierfamily25(mitochondrial carier;phosphatecarier),member25 PQloprepeatcontaining1 proteinphosphatase2,regulatorysubunita(pr65),betaisoform SERPINH1/Heatshockprotein47 zincfingerprotein295 epithelial membraneprotein1 LIMandSH3protein1 p14356 mrna Transforming,acidicoiled-coil containingprotein2 Ankyrin1,erythrocytic imediatearlyresponse2 chemokine(c-x3-cmotif)ligand1 phosphodiesterase7a Familywithsequencesimilarity36,memberA golgi autoantigen,golginsubfamilya,4 Krupel-likefactor2(lung) V-raf-1murineleukemiaviral oncogenehomolog1 earlygrowthresponse3 Krupel-likefactor4(gut) serine/threoninekinase38like neural precursorcel expresed,developmentalydown-regulated9 Semaphorin4C Ankylosis,progresivehomolog(mouse) Rasinteractingprotein1 Ras-likewithoutCAX1 lowdensitylipoproteinreceptor(familial hypercholesterolemia) ATPase,ClasI,type8B,member1 Elongationfactor,RNApolymeraseI,2 plasminogenactivator,urokinase testisderivedtranscript(3limdomains) proteinphosphatase1dmagnesium-dependent,deltaisoform nucleosidephosphorylase AXIN1up-regulated1 regulatorofg-proteinsignaling2,24kda KITligand STARTdomaincontaining4,sterol regulated Mortalityfactor4like2 solutecarierfamily2(facilitatedglucosetransporter),member3 Sirtuin(silentmatingtypeinformationregulation2homolog)2(S.cerevisiae) BTGfamily,member3 chemokine(c-cmotif)ligand8 Staniocalcin1 nucleareceptorsubfamily4,groupa,member2 ADAMTS9metaloprotease GTPcyclohydrolase1(dopa-responsivedystonia) FilaminB,beta(actinbindingprotein278) PCTAIREproteinkinase2 Musashi homolog2(drosophila) phorbol-12-myristate-13-acetate-inducedprotein1 Nexin,plasminogenactivatorinhibitortype1 deletedinlivercancer1 SimilartoD(1B)dopaminereceptor Actinin,alpha4 ADAMTS1metaloprotease Microtubule-asociatedprotein,RP/EBfamily,member2 MAXdimerizationprotein1 cysteine-rich,angiogenicinducer,61 proteinphosphatase1,regulatory(inhibitor)subunit15a chemokine(c-x-cmotif)ligand2 pleckstrinhomologydomaincontaining,familygmember1 heatshock105kda/10kdaprotein1 lysozyme(renal amyloidosis) mesenchymehomeobox1 ubiquitinspecificprotease2 myeloid/lymphoidormixed-lineageleukemia TPRdomain,ankyrin-repeatandcoiled-coil-containing programedcel death1ligand1 ChromodomainhelicaseDNAbindingprotein1 caldesmon1 ringfingerprotein138 RING1andY1bindingprotein CUGtripletrepeat,RNAbindingprotein2 tyrosine3-monoxygenase/tryptophan5-monoxygenaseactivationprotein,eta dynein,cytoplasmic,lightpolypeptide1 phosphatidylinositol bindingclathrinasemblyprotein tightjunctionprotein2(zonaocludens2) tribleshomolog1(drosophila) chlorideintracelularchanel 1 striatedmuscleactivatorofrho-dependentsignaling alpha-kinase3 DnaJ(Hsp40)homolog,subfamilyA,member1 mitogen-induciblegene6 zincfingerprotein36,c3htype-like1 Ankyrinrepeatdomain9 zincfinger,chcdomaincontaining2 cysteineandglycine-richprotein1 Akinase(PRKA)anchorprotein(gravin)12 zincfingerprotein36 nestin epithelial V-likeantigen1 endoglin(osler-rendu-webersyndrome1) N-mycdownstreamregulatedgene1 tubulin,beta2 discoidin,cubandlcldomaincontaining1 LIMprotein(similartoratproteinkinaseC-bindingenigma) ELOVLfamilymember5,elongationoflongchainfatyacids adrenergic,beta-2-,receptor,surface myeloid-asociatediferentiationmarker syntaxin12 ATrichinteractivedomain5B(MRF1-like) interferon-relatedevelopmental regulator1 tubulin,beta6 proteinphosphatase1,regulatory(inhibitor)subunit3e tubulin,alpha3 chemokine(c-cmotif)ligand2 Chr2synaptotagmin actin,alpha2,smothmuscle,aorta CAP,adenylatecyclase-asociatedprotein1(yeast) Exercise-induced transient gene responses mrna content Exercise Stress responsive genes 1-2 h recovery Metabolic genes 24 h recovery Time

163 Ex-0 Ex-3 Ex-6 Ex-9 Ex fatyacidbindingprotein3,muscleandheart tumorsupresordeletedinoral cancer-related1 heatshockprotein,alpha-crystalin-related,b6 carboxylesterase2(intestine,liver) glutaredoxin(thioltransferase) al-trans-13,14-dihydroretinol saturase cholinergicreceptor,nicotinic,alphapolypeptide1(muscle) purinergicreceptorp2x,ligand-gatedionchanel,5 colagen-liketail subunitofasymetricacetylcholinesterase angiomotinlike1 signal-inducedproliferation-asociated1like2 isocitratedehydrogenase3(nad+)alpha solutecarierfamily25(carnitine/acylcarnitinetranslocase),member20 mitochondrial protein18kda myosinbindingproteinh humanimuneasociatednucleotide6 Zincfingerprotein302 DNA-damage-inducibletranscript4-like Plasminogen-like growthdiferentiationfactor8 eukaryotictranslationinitiationfactor4a,isoform2 Thyroidhormonereceptorasociatedprotein1 Dystrobrevin,alpha Titinimunoglobulindomainprotein(myotilin) Semaphorin6D carbonicanhydraseiv regucalcingenepromotoregionrelatedprotein Dsiteofalbuminpromoter(albuminD-box)bindingprotein nuclearfactornf-kapa-binhibitoralpha Neuroserpin LIMdomainbinding2 thyroidhormonereceptor,alpha DAPK-interactingprotein1 Zincfinger,MYNDdomaincontaining17 synaptotagmin-like3 ankyrinrepeatdomain20a flavincontainingmonoxygenase2 CXCfinger6 Phosphonoformateimuno-asociatedprotein5 RAR-relatedorphanreceptorA dual specificityphosphatase10 Myocytenhancerfactor2C myosinx syntaxinbindingprotein6(amisyn) WDrepeatandSOCSbox-containing1 ectonucleotidepyrophosphatase/phosphodiesterase2(autotaxin) PDZdomaincontainingRINGfinger3 colagentriplehelixrepeatcontaining1 myosinregulatorylightchaininteractingprotein Sodiumchanel,voltage-gated,typeVI,alpha histonedeacetylase9 inhibitorofdnabinding2 myosin,heavypolypeptide10,non-muscle transmembraneprotein46 integrin,beta6 ATPase,(Na+)/K+transporting,beta4polypeptide ATPase,Ca+transporting,type2C,member1 meningiomaexpresedantigen6(coiled-coil proline-rich) phosphoinositide-3-kinase,clas2,betapolypeptide chemokine(c-x3-cmotif)receptor1 ubiquitinspecificprotease9,y-linked(fatfacets-like,drosophila) Ribosomal proteins23 ligand-dependentcorepresor mitogen-activatedproteinkinaseasociatedprotein1 aminomethyltransferase(glycinecleavagesystemproteint) membranemetalo-endopeptidase,cd10 Ankyrin3,nodeofRanvier(ankyrinG) glucocorticoidinducedtranscript1 phosphataseandactinregulator2 dual-specificitytyrosine-(y)-phosphorylationregulatedkinase2 mitogen-activatedproteinkinase9 tripartitemotif-containing45 TAF9-likeRNApolymeraseI zincfingerprotein252 LanClantibioticsynthetasecomponentC-like1(bacterial) alcohol dehydrogenaseib(clasi),betapolypeptide catenin(cadherin-asociatedprotein),delta1 fucosidase,alpha-l-1,tisue Rasasociation(RalGDS/AF-6)domainfamily4 basichelix-lop-helixdomaincontaining,clasb,3 nucleareceptorsubfamily1,groupd,member2 periodhomolog3(drosophila) vacuolarproteinsorting45a(yeast) unc-13homologb(c.elegans) nuclearfactornf-kapa-binhibitorkinase inter-alpha(globulin)inhibitorh4(plasmakalikrein-sensitiveglycoprotein) neural precursorcel expresed,developmentalydown-regulated1 Restin sonofsevenleshomolog2(drosophila) 2,3-bisphosphoglyceratemutase malicenzyme2,nad(+)-dependent,mitochondrial mesenchymal stemcel proteindsc54 tumorproteind52 uridine-cytidinekinase1-like1 secernin3 tripartitemotif-containing7 aquaporin4 dermatopontin putativelymphocyteg0/g1switchgene NuclearfactorI/B SETbindingprotein1 SERTAdomaincontaining2 transducin-likenhancerofsplit1 disheveledasociatedactivatorofmorphogenesis1 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase1 advilin GRB2-asociatedbindingprotein1 RhoGTPaseactivatingprotein18 adenylatecyclase2(brain) mucosasociatedlymphoidtisuelymphomatranslocationgene1 RAD51homologC(S.cerevisiae) CD38antigen(p45) Zincfinger,CHCdomaincontaining1 downregulatedinovariancancer1 pleckstrinhomologydomaininteractingprotein ankyrinrepeatandfyvedomaincontaining1 Endomucin Kelch-like1(Drosophila) inhibitorofdnabinding3 guanylatebindingprotein1,interferon-inducible,67kda v-ki-ras2kirstenratsarcomaviral oncogenehomolog fibronectinleucinerichtransmembraneprotein3 myeloidceleukemiasequence1(bcl2-related) Ubiquitin-conjugatingenzymeE2H(UBC8homolog,yeast) Rho-relatedBTBdomaincontaining1 inhibitorofdnabinding1 majorhistocompatibilitycomplex,clasi,dmalpha CD36antigen(colagentypeIreceptor,thrombospondinreceptor) Muscleblind-like(Drosophila) Sestrin1 DEAD(Asp-Glu-Ala-Asp)boxpolypeptide17 Partial mrnafort-cel receptorbetachain metalothionein1x adenosinemonophosphatedeaminase(isoforme) Catalase gangliosideinducediferentiationasociatedprotein2 Ependyminrelatedprotein1(zebrafish) RNAbindingmotifprotein6 imunoglobulinsuperfamily,member4 Proteinphosphatase1A,magnesium-dependent,alphaisoform Discs,largehomolog5(Drosophila) aryl hydrocarbonreceptornucleartranslocator-like splicingfactor1 Aryl hydrocarbonreceptornucleartranslocator insulin-likegrowthfactor1receptor familywithsequencesimilarity13,membera1 PogotransposablelementwithZNFdomain Abhydrolasedomaincontaining3 thioredoxininteractingprotein Ribosomal proteinl37a cytochromecoxidasesubunitviapolypeptide1 Wilmstumor1asociatedprotein Zincfingerprotein297B Fem-1homologa(C.elegans) Ribosomal proteins10 Iron-responsivelementbindingprotein2 Ribosomal proteinl27 ubiquitin-conjugatingenzymee2b(rad6homolog) HBxAgtransactivatedprotein2 ATPase,H+transporting,lysosomal 9kDa,V0subunite lungcancermetastasis-relatedprotein1 ribosomal proteinl38 Insulinreceptor CR4-NOTtranscriptioncomplex,subunit6-like Aminopeptidasepuromycinsensitive CytochromecoxidasesubunitVb Ribosomal proteins20 SourceofimunodominantMHC-asociatedpeptides Cysteine-richmotorneuron1 heatshock70kdaprotein1b zincfingerprotein403 Malatedehydrogenase1,NAD(soluble) FK506bindingprotein5 disheveledasociatedactivatorofmorphogenesis2 hexokinase2 trophoblast-derivednoncodingrna solutecarierfamily16(monocarboxylicacidtransporters),member7 Phosphodiesterase4D,cAMP-specific pyruvatedehydrogenasekinase,isoenzyme4 T-cel activationproteinphosphatase2c solutecarierfamily25,member5 estrogen-relatedreceptorgama Spermidine/spermineN1-acetyltransferase abhydrolasedomaincontaining2 translocaseofinermitochondrial membrane8homologa(yeast) muscledisease-relatedprotein fem-1homologb(c.elegans) proteintyrosinephosphatasedomaincontaining1 MethionineadenosyltransferaseI,alpha zincfingerprotein kDFMRPInteractingProtein histonedeacetylase4 nucleareceptorinteractingprotein1 kelchrepeatandbtb(poz)domaincontaining9 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 MAD2L1bindingprotein dysferlininteractingprotein1(tonin) signal-inducedproliferation-asociated1like3 Cholinephosphotransferase1 tumornecrosisfactoreceptorsuperfamily,member1a zincfingerprotein4(kox7) GTF2Irepeatdomaincontaining1 zincfingerprotein564 humanimunodeficiencyvirustypeienhancerbindingprotein2 pituitarytumor-transforming1interactingprotein myosin,heavypolypeptide9,non-muscle campresponsivelementmodulator solutecarierfamily19(thiaminetransporter),member2 aquaporin3 mitochondrial carierprotein ZincfingerandBTBdomaincontaining10 cryptochrome1(photolyase-like) lowdensitylipoproteinreceptor-relatedproteinbindingprotein UDP-glucoseceramideglucosyltransferase asparagine-linkedglycosylation2homolog TGFBinduciblearlygrowthresponse2 DnaJ(Hsp40)homolog,subfamilyB,member6 transcriptionfactor8(represesinterleukin2expresion) vestigialike2(drosophila) TGFBinduciblearlygrowthresponse Ras-relatedGTPbindingC LATS,largetumorsupresor,homolog2(Drosophila) nucleosomeasemblyprotein1-like5 moesin chlorideintracelularchanel 4 TGFB-inducedfactor(TALEfamilyhomeobox) actin,beta anexina3 insulinreceptorsubstrate2 tisueinhibitorofmetaloproteinase3 cofactorequiredforsp1transcriptional activation,subunit7,70kda coronin,actinbindingprotein,1c TBC1domainfamily,member14 chemokineorphanreceptor1 retinoblastomabindingprotein6 Transientreceptorpotential cationchanel,subfamilym,member7 tryptophanyl-trnasynthetase Jumonji,ATrichinteractivedomain2 thrombospondin1 microtubuleasociatedmonoxygenase,calponinandlim2 zincfingerprotein31 solutecarierfamily1(proton-coupledivalentmetal iontransporters),member2 hairy/enhancer-of-splitrelatedwithyrpwmotif1 ATPase,Na+/K+transporting,beta3polypeptide RAB20,memberRASoncogenefamily v-mafmusculoaponeuroticfibrosarcomaoncogenehomologf(avian) breastcanceranti-estrogenresistance3 TEKtyrosinekinase,endothelial tropomyosin4 FOS-likeantigen2 phosphatidylinositol transferprotein,cytoplasmic1 cytoplasmicpolyadenylationelementbindingprotein4 selenophosphatesynthetase2 vascularendothelial growthfactor peripheral myelinprotein2 v-mafmusculoaponeuroticfibrosarcomaoncogenehomologk(avian) fourandahalflimdomains2 sphingomyelinphosphodiesterase,acid-like3a angiopoietin-like4 Myelinbasicprotein Bcel RAGasociatedprotein nuclearfactor,interleukin3regulated nucleareceptorsubfamily4,groupa,member3 tumorproteinp73-like GABA(A)receptor-asociatedproteinlike1 Supresorofcytokinesignaling7 CHMP1.5protein interleukin6receptor angiopoietin-like2 pim-3oncogene salt-inducibleserine/threoninekinase2 v-etserythroblastosisviruse26oncogenehomolog2(avian) Sexcombonmidleg-like1(Drosophila) stomatin RAR-relatedorphanreceptorC MAXgeneasociated interleukin1receptor,typei peroxisomeproliferativeactivatedreceptor,gama,coactivator1,alpha forkheadboxo1a(rhabdomyosarcoma) Guaninenucleotidebindingprotein(Gprotein),alpha13 interferon,gama-inducibleprotein16 colagen,typeiv,alpha1 solutecarierfamily2(organicationtransporter),member5 SH3-domainbindingprotein5(BTK-asociated) TBC1domainfamily,member8(withGRAMdomain) potasiumvoltage-gatedchanel,kqt-likesubfamily,member4 ZincfingerandBTBdomaincontaining16 RNA,U2smal nucleolar Epidermal growthfactoreceptorpathwaysubstrate15-like1 pericentrin2(kendrin) basichelix-lop-helixdomaincontaining,clasb,2 mitogen-activatedproteinkinasekinasekinase2 hairy/enhancer-of-splitrelatedwithyrpwmotif2 phospholipidscramblase1 glucosamine-6-phosphatedeaminase1 Ubiquitinspecificprotease36 endothelial diferentiation,sphingolipidg-protein-coupledreceptor,3 synaptojanin2 esterase31 platelet/endothelial cel adhesionmolecule(cd31antigen) adrenomedulin Bicaudal Dhomolog1(Drosophila) Proteinkinase,AMP-activated,gama2non-catalyticsubunit Proteinkinase,cGMP-dependent,typeI Spectrin,beta,erythrocytic(includespherocytosis,clinical typei) Proteinphosphatase1,regulatory(inhibitor)subunit12B forkheadboxo3a frizledhomolog7(drosophila) eukaryotictranslationinitiationfactor2-alphakinase3 jundproto-oncogene SERTAdomaincontaining1 SorbinandSH3domaincontaining1 zyxin actin,gama1 integrin,alpha5(fibronectinreceptor,alphapolypeptide) Epidermal growthfactoreceptor fourandahalflimdomains5 periodhomolog2(drosophila) periodhomolog1(drosophila) Fms-relatedtyrosinekinase1(vegf/vpfreceptor) Nucleareceptorsubfamily3,groupC,member1(glucocorticoidreceptor) Isopentenyl-diphosphatedeltaisomerase arestindomaincontaining4 plexina2 dual specificityphosphatase1 Zincfingerprotein146 solutecarierfamily20(phosphatetransporter),member1 tumornecrosisfactoreceptorsuperfamily,member10b metastasisasociatedlungadenocarcinomatranscript1 smal proteinefector1ofcdc42 GTPbindingproteinoverexpresedinskeletal muscle Zincfingersandhomeoboxes2 brainandreproductiveorgan-expresed(tnfrsf1amodulator) spectrinrepeatcontaining,nuclearenvelope1 prostaglandinereceptor4(subtypeep4) FERMdomaincontaining4A glycoproteinarepetitionspredominant conectivetisuegrowthfactor karyopherinalpha2(ragcohort1,importinalpha1) RNAbindingproteinwithmultiplesplicing solutecarierfamily25(mitochondrial carier;phosphatecarier),member25 PQloprepeatcontaining1 proteinphosphatase2,regulatorysubunita(pr65),betaisoform SERPINH1/Heatshockprotein47 zincfingerprotein295 epithelial membraneprotein1 LIMandSH3protein1 p14356 mrna Transforming,acidicoiled-coil containingprotein2 Ankyrin1,erythrocytic imediatearlyresponse2 chemokine(c-x3-cmotif)ligand1 phosphodiesterase7a Familywithsequencesimilarity36,memberA golgi autoantigen,golginsubfamilya,4 Krupel-likefactor2(lung) V-raf-1murineleukemiaviral oncogenehomolog1 earlygrowthresponse3 Krupel-likefactor4(gut) serine/threoninekinase38like neural precursorcel expresed,developmentalydown-regulated9 Semaphorin4C Ankylosis,progresivehomolog(mouse) Rasinteractingprotein1 Ras-likewithoutCAX1 lowdensitylipoproteinreceptor(familial hypercholesterolemia) ATPase,ClasI,type8B,member1 Elongationfactor,RNApolymeraseI,2 plasminogenactivator,urokinase testisderivedtranscript(3limdomains) proteinphosphatase1dmagnesium-dependent,deltaisoform nucleosidephosphorylase AXIN1up-regulated1 regulatorofg-proteinsignaling2,24kda KITligand STARTdomaincontaining4,sterol regulated Mortalityfactor4like2 solutecarierfamily2(facilitatedglucosetransporter),member3 Sirtuin(silentmatingtypeinformationregulation2homolog)2(S.cerevisiae) BTGfamily,member3 chemokine(c-cmotif)ligand8 Staniocalcin1 nucleareceptorsubfamily4,groupa,member2 ADAMTS9metaloprotease GTPcyclohydrolase1(dopa-responsivedystonia) FilaminB,beta(actinbindingprotein278) PCTAIREproteinkinase2 Musashi homolog2(drosophila) phorbol-12-myristate-13-acetate-inducedprotein1 Nexin,plasminogenactivatorinhibitortype1 deletedinlivercancer1 SimilartoD(1B)dopaminereceptor Actinin,alpha4 ADAMTS1metaloprotease Microtubule-asociatedprotein,RP/EBfamily,member2 MAXdimerizationprotein1 cysteine-rich,angiogenicinducer,61 proteinphosphatase1,regulatory(inhibitor)subunit15a chemokine(c-x-cmotif)ligand2 pleckstrinhomologydomaincontaining,familygmember1 heatshock105kda/10kdaprotein1 lysozyme(renal amyloidosis) mesenchymehomeobox1 ubiquitinspecificprotease2 myeloid/lymphoidormixed-lineageleukemia TPRdomain,ankyrin-repeatandcoiled-coil-containing programedcel death1ligand1 ChromodomainhelicaseDNAbindingprotein1 caldesmon1 ringfingerprotein138 RING1andY1bindingprotein CUGtripletrepeat,RNAbindingprotein2 tyrosine3-monoxygenase/tryptophan5-monoxygenaseactivationprotein,eta dynein,cytoplasmic,lightpolypeptide1 phosphatidylinositol bindingclathrinasemblyprotein tightjunctionprotein2(zonaocludens2) tribleshomolog1(drosophila) chlorideintracelularchanel 1 striatedmuscleactivatorofrho-dependentsignaling alpha-kinase3 DnaJ(Hsp40)homolog,subfamilyA,member1 mitogen-induciblegene6 zincfingerprotein36,c3htype-like1 Ankyrinrepeatdomain9 zincfinger,chcdomaincontaining2 cysteineandglycine-richprotein1 Akinase(PRKA)anchorprotein(gravin)12 zincfingerprotein36 nestin epithelial V-likeantigen1 endoglin(osler-rendu-webersyndrome1) N-mycdownstreamregulatedgene1 tubulin,beta2 discoidin,cubandlcldomaincontaining1 LIMprotein(similartoratproteinkinaseC-bindingenigma) ELOVLfamilymember5,elongationoflongchainfatyacids adrenergic,beta-2-,receptor,surface myeloid-asociatediferentiationmarker syntaxin12 ATrichinteractivedomain5B(MRF1-like) interferon-relatedevelopmental regulator1 tubulin,beta6 proteinphosphatase1,regulatory(inhibitor)subunit3e tubulin,alpha3 chemokine(c-cmotif)ligand2 Chr2synaptotagmin actin,alpha2,smothmuscle,aorta CAP,adenylatecyclase-asociatedprotein1(yeast) Exercise-induced transient gene responses mrna content Exercise Stress responsive genes 1-2 h recovery Metabolic genes Oxidative enzyme genes 24 h recovery Time

164 The Biobank Satelite cells will be isolated from human skeletal muscle cells, derived from muscle biopsies from well characterised individuals..

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