Expression pattern of E2F6 in physical and chemical hypoxia-induced apoptosis

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SHU Bo(Laboratory of Molecular Cardiology of Institute of Health Sciences,Shanghai Jiao Tong University School of Medicine(SJTUSM) and Shanghai Institutes for Biological Sciences(SIBS),Chinese Academy of Sciences(CAS),Shanghai 200025,China)
YANG Wei-Wei(Laboratory of Molecular Cardiology of Institute of Health Sciences,SIBS,CAS and SJTUSM,Shanghai 200025,China)
YANG Huang-Tian(Laboratory of Molecular Cardiology of Institute of Health Sciences,SIBS,CAS and SJTUSM,Shanghai 200025,China)
Journal Title:
Volume 60, Issue 01, 2008
Key Word:
E2F6;apoptosis;physical hypoxia;cobalt chloride;desferrioxamine;H9c2 cells

Abstract´╝Ü Apoptosis can be caused by hypoxia,a major factor during ischemic injury,in cardiomyocytes.However,the regulatory mechanisms underlying hypoxia-induced cardiomyocyte apoptosis have not yet been fully understood.E2F6,an identified E2F family member,has been demonstrated to repress DNA damage-induced apoptosis in our recent study.HoweveL it is unclear whether E2F6 is involved in hypoxia-induced apoptosis.In this study,we determined the expression property of E2F6 during hypoxia-induced apoptosis in H9c2 cells,a rat ventricular myoblast cell line.The results showed that physical hypoxia and chemical hypoxia-mimetic agents desferrioxamine(DFO)and cobalt chloride(CoCl2)induced apoptosis in H9c2 cells.Physical hypoxia-and CoCl2-induced apoptosis was accompanied with a downregulation of endogenous E2F6 mRNA expression,but not protein expression.DFO treatment resulted in a significant downregulation of both mRNA and protein expressions of endogenous E2F6.These results suggest that E2F6 may be involved in DFO-induced apoptosis,while it is less sensitive in physical hypoxia-and CoCl2-induced apoptosis in H9c2 cells.In addition,the apoptosis induced by DFO may share different pathways from that induced by physical hypoxia and CoCl2.

  • [1]Hajra KM.Liu JR.Apoptosome dysfunction in human cancer.Apoptosis 2004;9:691-704.
  • [2]Krijnen PA,Nijmeijer R,Meijer CJ,Visser CA,Hack CE,Niessen SHU Bo et al:E2F6 Expression in Hypoxia-induced Apoptosis HW.Apoptosis in myocardial ischaemia and infarction.J Clin Patho12002; 55:801-811.
  • [3]Kang PM,Izumo S.Apoptosis and heart failure:a critical review of the literature.Circ Res 2000; 86:1107-1113.
  • [4]Mehrhof FB,Muller FU,Bergnmnn MW,Li P,Wang Y,Schmitz W,Dietz IL yon Harsdoff R.In cardiomyocyte hypoxia,insulinlike growth factor-I-induced antiapoptotic signaling requires phosphatidylinositol-3-OH-kinase-dependent and mitogen-activated protein kinase-depondent activation of the transcription factor cAMP response element-binding protein.Circulation 2001;104:2088-2094.
  • [5]Bialik S,Geenen DL,Sasson IE,Cbeng R,Home JW,Evans SM,Lord EM,Koch CJ,Kitsis RN.Myocyte apoptosis during acute myocardial infarction in the mouse localizes to hypoxic regions but occurs independently.J Clin Invest 1997; 100:1363-1372.
  • [6]Kang PM,Haunstetter A,Aoki H,Usheva A,Izumo S.Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and re.oxygenation.Circ Res 2000; 87:118-125.
  • [7]Trimarchi JM,Lees JA.Sibling rivalry in the E2F family.Nat Rev Mol Cell Biol 2002; 3:11-20.
  • [8]Kowalik TF,DeGregori J,Schwarz JK,Nevins JR.E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis.J Virol 1995; 64:2491-2500.
  • [9]DeGregori J.The genetics of the E2F family of transcription factors:shared functions and unique roles.Biochim Biophys Acta 2002; 1602:131-150.
  • [10]Agah R,Kirshenbaum LA,Abdellatif M,Tmong LD,Chakraborty S,Michael LH,Schneider MD.Adenoviral delivery of E2F-1 directs cell cycle reentry and p53-independent apoptosis in postmitotic adult myocardium in vivo.J Clin Invest 1997; 100:2722-2728.
  • [11]Ebelt H,Hufnagel N,Neuhaus P,Neuhaus H,Gajawada P,Simm A,Mtiller-Werdan U,Werdan K,Braun T.Divergent siblings:E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis.Circ Res 2005; 96:509-517.
  • [12]Trimarchi JM,Fairchild B,Verona IL Moberg K,Andon N,Lees JA.E2F-6,a member of the E2F family that can behave as a transcriptional repressor.Proc Natl Acad Sci USA 1998; 95:2850-2855.
  • [13]Trimarchi JM,Fairchild B,Wen J,Lees JA.The E2F6 transcription factor is a component of the mammalian Broil-containing polycomb complex.Proc Nail Acad Sci USA 2001; 98:1519-1524.
  • [14]Ogawa H,Ishiguro K,Gaubatz S,Livingston DM,Nakatani Y.A complex with chromatin modifiers that occupies E2F-and Myc-responsive genes in Go cells.Science 2002; 296:1132-1136.
  • [15]Yang WW,Wang ZH,Zhu Y,Yang HT.E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1.Cell Death Differ 2007; 14:807-817.
  • [16]Kimes BW,Brandt BL.Properties of a clonal muscle cell line from rat heart.Exp Cell Res 1976; 98:367-381.
  • [17]An WG,Kanekal M,Simon MC,Maltepe E,Blagosklonny MV,Neckers LM.Stabilization of wild-type p53 by hypoxiainducible factor Ict.Nature 1998; 392:405-408.
  • [18]Yang S J,Pyen J,Lee I,Lee H,Kim Y,Kim T.Cobalt chloride induced apoptosis and extracellular signal-regulated protein kinase 1/2 activation in rat (26 glioma cells.J Biochem Mol Biol 2004; 37:480-486.
  • [19]Lee SK,Jang HJ,Lee HJ,Lee J,Jeon BH,Jun CD,Lee SK,Kim EC.p38 and ERK MAP kinase mediates iron chelator-induced apoptosis and -suppressed differentiation of immortalized and malignant human oral keratinocytes.Life Sci 2006; 79:1419-1427.
  • [20]Sakarnoto K,Urushidani T,Nagao T.Translocation of HSP27 to cytoskeleton by repetitive hypoxia-reoxygenation in the rat myoblast cell line,H9c2.Biocbem Biophys Res Commun 1998;251:576-579.
  • [21]Araya J,Maruyama M,Inoue A,Fujita T,Kawahara J,Sassa K,Hayashi R,Kawagishi Y,Yamashita N,Sugiyama E,Kobayashi M.Inhibition of proteasome activity is involved in cobalt-induced apoptosis of human alveolar maerophages.Am J Physiol Lung Cell Mol Physiol 2002; 283:849-858.
  • [22]Mecklenburgh KI,Walmsley SR,Cowburn AS,Wiesener M,Reed B J,Upton PD,Deighton J,Greening AP,Chilvers ER.Involvemem of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis.Blood 2002; 100:3008-3016.
  • [23]Scully R,Chen J,Ochs RL,Keegan K,Hoekstra M,Feunteun J,Livingston DM.Dynamic changes of BRCA1 subnuclear location and phosphorylation state are initiated by DNA damage.Ceil 1997; 90:425-435.
  • [24]Zhou D,Chen S.Characterization of a silencer element in the human aromatase gene.Arch Biochem Biophys 1998; 353:213-220.
  • [25]Debatin KM.Apoptosis pathways in cancer and cancer therapy.Cancer Immunol Immunother 2004; 53:153-159.
  • [26]Oliver G,Abbi R,Quaini F,Kajstura J,Cheng W,Nitahara JA,Quaini E,Di Loreto C,Beltrami CA,Krajewski S,Reed JC,Anversa P.Apoptosis in the failing human heart.N Engl J Med 1997; 336:1131-1141.
  • [27]Narula J,Haider N,Virrnani R,DiSalvo TG,Kolodgie FD,Hajjar RJ,Schmidt U,Semigran MJ,Dec GW,Khaw BA.Apoptosis in myocytes in end-stage heart failure.N Engl J Med 1996; 335:1182-1189.
  • [28]Saraste A,Pulkki K,Kallajoki M,Henriksen K,Parvinen M,Voipio-Pulkki LM.Apoptosis in human acute myocardial infarction.Circulation 1997; 95:320-323.
  • [29]Long X,Boluyt MO,Hipolito ML,Lundberg MS,Zheng JS,O'NeillLCh-iclliC,LakattaEG,CrowMT.p53andthehypoxiainduced apoptosis of cultured neonatal rat cardiac myocytes.J Clin Invest 1997;99:2635-2643.
  • [30]Movassagh M,Bicknell KA,Brooks G.Characterisation and regulation of E2F-6a and E2F-6b in the mt heart:a potential targetformyocardialregeneration?JPharlnPharmac012006;58:73-82.
  • [31]Hauck L,Harlsnlann G,Dietz R,yonHarsdorf R.Inhibition of hypoxia-induced apoptosis by modulation of retinoblastoma protein-dependent signaling in cardiomyocytes.Circ Res 2002;91:782-789.
  • [32]Wang GL,Semenza GL.General involvement ofhypoxia-induciblefactorl transcriptional response to hypoxia Proc Natl Acad Sci USA 1993:90:4304-4308.
  • [33]Wang GL,SemenzaGL.Desferdoxamineinduceserythropoietin gene expression and hypoxia-inducible factor l DNA-binding activity:implications for models of hypoxia signal transducfion.Blood 1993;82:3610-3615.
  • [34]Woo KJ,Lee TJ,Park JW,Kwon TK.Desferrioxamine,an iron chelator,enhances HIF-Ia accumulation via cyclooxygenase-2signaling pathway.Biochem Biophys Res Commun 2006;343:8-14.
  • [35]Groenman FA,Rutter M,Wang J,Caniggia I,Tibboel D,Post Acta Physiologica Sinica,February 25,2008,60(1):1-10M.Effect of chemical stabilizers of hypoxia inducible factors on early lung development.Am J Physiol Lung Cen Mol Physiol 2007:293:557-567.
  • [35]Groenman FA,Rutter M,Wang J,Caniggia I,Tibboel D,Post Acta Physiologica Sinica,February 25,2008,60(1):1-10M.Effect of chemical stabilizers of hypoxia inducible factors on early lung development.Am J Physiol Lung Cen Mol Physiol 2007:293:557-567.
  • [36]VengeUur A,Phillips JM,Hogenesch JB,LaPres JJ.Gene expression profiling ofhypoxia signaling in human hepatocellular carcinoma cells.Physiol Genomics 2005;22:408-418.
  • [37]Adams JM,Cory S.The Bcl-2 protein family:arbiters of cell survival.Science 1998:281:1322-1326.
  • [38]Green DR,Reed JC.Mitochondria and apoptosis.Science 1998;281:1309-1312.
  • [39]Pulido MD.Pardsh AR.Metal-induced apoptosis:mechanisms.Mutat Res 2003:533:227-241.
  • [40]Kim BM,Choi JY,Kim YJ,Woo HD,Chung HW.Desferrioxamine(DFX)has genotoxic effects oncultured human lym phocytes and induces the p53-mediated damagere sponse.Toxicology 2007;229:226-235.
  • [41]Guo M,Song LP,Jiang Y,Liu W,Yu Y,Chen GQ.Hypoxiamimetic agents desferrioxamine and cobalt chloride induce leukemic cell apoptosis through different hypoxia-inducible factorla independent mechanisms.Apoptosis 2006;11:67-77.
  • [42]Gegelashvili G.Schousboe A.High affinity glutamate transporters:regulation of expression and activity.Mol Pharmacol 1997;52:6-15.
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