Circulation Research, Vol 75, 426-433, Copyright © 1994 by American Heart Association

ARTICLES

Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes

M Tanaka, H Ito, S Adachi, H Akimoto, T Nishikawa, T Kasajima, F Marumo and M Hiroe
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.

We examined whether apoptosis occurs in cardiomyocytes by hypoxia in vitro. Neonatal rat cardiomyocytes and nonmyocytes were cultured in 95% N2-5% CO2 atmosphere to produce hypoxic conditions. DNA fragmentation into integer multiples of the internucleosomal DNA length was observed in cardiomyocytes as early as 12 hours, whereas nonmyocytes did not show fragmentation of DNA up to 72 hours. DNA fragmentation of cardiomyocytes induced by hypoxia was also confirmed by nick-end labeling in situ. Messenger RNA for Fas antigen, a mediator of apoptotic cell death, was expressed in both cardiomyocytes and nonmyocytes as revealed by Northern blotting and in situ hybridization. In hypoxic condition, Fas messenger RNA levels in cardiomyocytes were upregulated by twofold over controls, whereas those of nonmyocytes were downregulated. These results indicate that cardiomyocyte death by hypoxia can occur via apoptosis and that Fas antigen may be associated with the mechanism of this apoptotic process.

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				D. Li, B. Yang, and J. L. Mehta Tumor necrosis factor-{alpha} enhances hypoxia-reoxygenation-mediated apoptosis in cultured human coronary artery endothelial cells: critical role of protein kinase C Cardiovasc Res, June 1, 1999; 42(3): 805 - 813. [Abstract] [Full Text] [PDF]

				R. Malhotra and F. C. Brosius III Glucose Uptake and Glycolysis Reduce Hypoxia-induced Apoptosis in Cultured Neonatal Rat Cardiac Myocytes J. Biol. Chem., April 30, 1999; 274(18): 12567 - 12575. [Abstract] [Full Text] [PDF]

				M. W. Irwin, S. Mak, D. L. Mann, R. Qu, J. M. Penninger, A. Yan, F. Dawood, W.-H. Wen, Z. Shou, and P. Liu Tissue Expression and Immunolocalization of Tumor Necrosis Factor-{alpha} in Postinfarction Dysfunctional Myocardium Circulation, March 23, 1999; 99(11): 1492 - 1498. [Abstract] [Full Text] [PDF]

				C. Kawai From Myocarditis to Cardiomyopathy: Mechanisms of Inflammation and Cell Death : Learning From the Past for the Future Circulation, March 2, 1999; 99(8): 1091 - 1100. [Abstract] [Full Text] [PDF]

				H. Chan, D. P. Bartos, and L. B. Owen-Schaub Activation-Dependent Transcriptional Regulation of the Human fas Promoter Requires NF-kappa B p50-p65 Recruitment Mol. Cell. Biol., March 1, 1999; 19(3): 2098 - 2108. [Abstract] [Full Text] [PDF]

				G.-W. Wang, D. A. Schuschke, and Y. J. Kang Metallothionein-overexpressing neonatal mouse cardiomyocytes are resistant to H2O2 toxicity Am J Physiol Heart Circ Physiol, January 1, 1999; 276(1): H167 - H175. [Abstract] [Full Text] [PDF]

				D. Li, K. Tomson, B. Yang, P. Mehta, B. P. Croker, and J. L. Mehta Modulation of constitutive nitric oxide synthase, bcl-2 and Fas expression in cultured human coronary endothelial cells exposed to anoxia-reoxygenation and angiotensin II: role of AT1 receptor activation Cardiovasc Res, January 1, 1999; 41(1): 109 - 115. [Abstract] [Full Text] [PDF]

				G Taimor, H Lorenz, B Hofstaetter, K.-D Schluter, and H.M Piper Induction of necrosis but not apoptosis after anoxia and reoxygenation in isolated adult cardiomyocytes of rat Cardiovasc Res, January 1, 1999; 41(1): 147 - 156. [Abstract] [Full Text] [PDF]

				S. Ishiyama, M. Hiroe, T. Nishikawa, T. Shimojo, S. Abe, H. Fujisaki, H. Ito, K. Yamakawa, N. Kobayashi, T. Kasajima, et al. The Fas/Fas Ligand System Is Involved in the Pathogenesis of Autoimmune Myocarditis in Rats J. Immunol., November 1, 1998; 161(9): 4695 - 4701. [Abstract] [Full Text] [PDF]

				M. E. Miranda, C.-E Tseng, W. Rashbaum, R. L. Ochs, C. A. Casiano, F. Di Donato, E. K. L. Chan, and J. P. Buyon Accessibility of SSA/Ro and SSB/La Antigens to Maternal Autoantibodies in Apoptotic Human Fetal Cardiac Myocytes J. Immunol., November 1, 1998; 161(9): 5061 - 5069. [Abstract] [Full Text] [PDF]

				E. A Woodcock, S. J Matkovich, and O. Binah Ins(1,4,5)P3 and cardiac dysfunction Cardiovasc Res, November 1, 1998; 40(2): 251 - 256. [Full Text] [PDF]

				C. Communal, K. Singh, D. R. Pimentel, and W. S. Colucci Norepinephrine Stimulates Apoptosis in Adult Rat Ventricular Myocytes by Activation of the ß-Adrenergic Pathway Circulation, September 29, 1998; 98(13): 1329 - 1334. [Abstract] [Full Text] [PDF]

				D. de Moissac, S. Mustapha, A. H. Greenberg, and L. A. Kirshenbaum Bcl-2 Activates the Transcription Factor NFkappa B through the Degradation of the Cytoplasmic Inhibitor Ikappa Balpha J. Biol. Chem., September 11, 1998; 273(37): 23946 - 23951. [Abstract] [Full Text] [PDF]

				D. Li, B. Yang, and J. L. Mehta Ox-LDL induces apoptosis in human coronary artery endothelial cells: role of PKC, PTK, bcl-2, and Fas Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H568 - H576. [Abstract] [Full Text] [PDF]

				A. Goussev, V. G. Sharov, H. Shimoyama, M. Tanimura, M. Lesch, S. Goldstein, and H. N. Sabbah Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure Am J Physiol Heart Circ Physiol, August 1, 1998; 275(2): H626 - H631. [Abstract] [Full Text] [PDF]