Variation of NDRG2 and c-Myc expression in rat heart during the acute stage of ischemia/reperfusion injury
Tóm tắt
N-Myc downstream regulated gene 2 (NDRG2), a Myc-repressed gene, is highly expressed in heart tissue. NDRG2 increases in response to hypoxia-induced stress and is involved in hypoxia-induced radioresistance. However, little is known about the expression changes and possible roles of NDRG2 in the heart under hypoxia condition. Here, the authors show that NDRG2, mainly localized in cardiomyocyte cytoplasm, was significantly reduced in myocardial tissue after acute ischemia/reperfusion (I/R) injury. Meanwhile, c-Myc was up-regulated following acute I/R injury, and the expression of c-Myc was significantly inversely correlated with that of NDRG2. In addition, overexpression of c-Myc in primary cultured cardiomyocyte repressed NDRG2 expression. Furthermore, the increase of cardiomyocyte apoptosis was correlated with the decrease of NDRG2 protein during the acute phase of reperfusion. These data suggested for the first time that I/R injury-induced up-regulation of pro-apoptotic c-Myc expression may contribute to the down-regulation of anti-apoptotic NDRG2. This stress response might be involved in the novel mechanism of myocardial apoptosis induced by I/R injury in rat.
Tài liệu tham khảo
Askew DS, Ashmun RA, Simmons BC, Cleveland JL (1991) Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 6:1915–1922
Boulkroun S, Fay M, Zennaro MC, Escoubet B, Jaisser F, Blot-Chabaud M, Farman N, Courtois-Coutry N (2002) Characterization of rat NDRG2 (N-Myc downstream regulated gene 2), a novel early mineralocorticoid-specific induced gene. J Biol Chem 277:31506–31515
Brunelle JK, Santore MT, Budinger GR, Tang Y, Barrett TA, Zong WX, Kandel E, Keith B, Simon MC, Thompson CB, Hay N, Chandel NS (2004) c-Myc sensitization to oxygen deprivation-induced cell death is dependent on Bax/Bak, but is independent of p53 and hypoxia-inducible factor-1. J Biol Chem 279:4305–4312
Burchfield JG, Lennard AJ, Narasimhan S, Hughes WE, Wasinger VC, Corthals GL, Okuda T, Kondoh H, Biden TJ, Schmitz-Peiffer C (2004) Akt mediates insulin-stimulated phosphorylation of Ndrg2: evidence for cross-talk with protein kinase C theta. J Biol Chem 279:18623–18632
Condorelli G, Roncarati R, Ross J Jr, Pisani A, Stassi G, Todaro M, Trocha S, Drusco A, Gu Y, Russo MA, Frati G, Jones SP, Lefer DJ, Napoli C, Croce CM (2001) Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function. Proc Natl Acad Sci USA 98:9977–9982
Deloche A, Fabiani JN, Camilleri JP, Relland J, Joseph D, Carpentier A, Dubost C (1977) The effect of coronary artery reperfusion on the extent of myocardial infarction. Am Heart J 93:358–366
Deng Y, Yao L, Liu X (2001) Exploring a new gene containing ACP like domain in human brain and expression of it in E. coli. Prog Biochem Biophys 28:72–76
Deng Y, Yao L, Chau L, Ng SS, Peng Y, Liu X, Au WS, Wang J, Li F, Ji S, Han H, Nie X, Li Q, Kung HF, Leung SY, Lin MC (2003) N-Myc downstream-regulated gene 2 (NDRG2) inhibits glioblastoma cell proliferation. Int J Cancer 106:342–347
Esumi K, Nishida M, Shaw D, Smith TW, Marsh JD (1991) NADH measurements in adult rat myocytes during simulated ischemia. Am J Physiol 260:H1743–H1752
Green DR, Reed JC (1998) Mitochondria and apoptosis. Science 281:1309–1312
Hu XL, Liu XP, Deng YC, Lin SX, Wu L, Zhang J, Wang LF, Wang XB, Li X, Shen L, Zhang YQ, Yao LB (2006) Expression analysis of the NDRG2 gene in mouse embryonic and adult tissues. Cell Tissue Res 325:67–76
Huang CY, Fujimura M, Noshita N, Chang YY, Chan PH (2001) SOD1 down-regulates NF-kappaB and c-Myc expression in mice after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21:163–173
Klefstrom J, Västrik I, Saksela E, Valle J, Eilers M, Alitalo K (1994) c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha. EMBO J 13:5442–5450
Lefer DJ, Granger DN (2000) Oxidative stress and cardiac disease. Am J Med 109:315–323
Liu J, Zhang J, Wang X, Li Y, Chen Y, Li K, Zhang J, Yao L, Guo G (2010a) HIF-1 and NDRG2 contribute to hypoxia-induced radioresistance of cervical cancer Hela cells. Exp Cell Res 316(12):1985–1993
Liu S, Yang P, Kang H, Lu L, Zhang Y, Pan J, Rui YC (2010b) NDRG2 induced by oxidized LDL in macrophages antagonizes growth factor productions via selectively inhibiting ERK activation. Biochim Biophys Acta 1801:106–113
Lusis EA, Watson MA, Chicoine MR, Lyman M, Roerig P, Reifenberger G, Gutmann DH, Perry A (2005) Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma. Cancer Res 65:7121–7126
Ma H, Zhang HF, Yu L, Zhang QJ, Li J, Hou JH, Li X, Guo WY, Wang HC, Gao F (2006) Vasculoprotective effect of insulin in the ischemic/reperfused canine heart: role of Akt-stimulated NO production. Cardiovasc Res 69:57–65
Ma J, Jin H, Wang H, Yuan J, Bao T, Jiang X, Zhang W, Zhao H, Yao L (2008) Expression of NDRG2 in clear cell renal cell carcinoma. Biol Pharm Bull 31:1316–1320
Matsui H, Motooka M, Koike H, Inoue M, Iwasaki T, Suzuki T, Kurabayashi M, Yokoyama T (2007) Ischemia/reperfusion in rat heart induces leptin and leptin receptor gene expression. Life Sci 80:672–680
Mitchelmore C, Büchmann-Møller S, Rask L, West MJ, Troncoso JC, Jensen NA (2004) NDRG2: a novel Alzheimer’s disease associated protein. Neurobiol Dis 16:48–58
Okuda T, Kondoh H (1999) Identification of new genes ndr2 and ndr3 which are related to Ndr1/RTP/Drg1 but show distinct tissue specificity and response to N-myc. Biochem Biophys Res Commun 266:208–215
Oyama J, Blais C Jr, Liu X, Pu M, Kobzik L, Kelly RA, Bourcier T (2004) Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. Circulation 109:784–789
Piacentini L, Karliner JS (1999) Altered gene expression during hypoxia and reoxygenation of the heart. Pharmacol Ther 83:21–37
Takahashi K, Yamada M, Ohata H, Honda K, Yamada M (2005) Ndrg2 promotes neurite outgrowth of NGF-differentiated PC12 cells. Neurosci Lett 388:157–162
Verma S, Fedak PW, Weisel RD, Butany J, Rao V, Maitland A, Li RK, Dhillon B, Yau TM (2002) Fundamentals of reperfusion injury for the clinical cardiologist. Circulation 105:2332–2336
Vila-Petroff M, Salas MA, Said M, Valverde CA, Sapia L, Portiansky E, Hajjar RJ, Kranias EG, Mundiña-Weilenmann C, Mattiazzi A (2007) CaMKII inhibition protects against necrosis and apoptosis in irreversible ischemia-reperfusion injury. Cardiovasc Res 73:689–698
Wang L, Liu N, Yao L, Li F, Zhang J, Deng Y, Liu J, Ji S, Yang A, Han H, Zhang Y, Zhang J, Han W, Liu X (2008) NDRG2 is a new HIF-1 target gene necessary for hypoxia-induced apoptosis in A549 cells. Cell Physiol Biochem 21:239–250
Wechsler AS, Entwistle JC 3rd, Yeh T Jr, Ding M, Jakoi ER (1994) Early gene changes in myocardial ischemia. Ann Thorac Surg 58:1282–1284
Yang J, Li Y, Wu L, Zhang Z, Han T, Guo H, Jiang N, Tao K, Ti Z, Liu X, Yao L, Dou K (2010) NDRG2 in rat liver regeneration: role in proliferation and apoptosis. Wound Repair Regen 18:524–531
Zhang J, Li F, Liu X, Shen L, Liu J, Su J, Zhang W, Deng Y, Wang L, Liu N, Han W, Zhang J, Ji S, Yang A, Han H, Yao L (2006) The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter. J Biol Chem 281:39159–39168
Zhou RH, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T (2001) Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Genomics 73:86–97