doi: 10.1161/01.RES.0000030195.38795.CF
© 2002 American Heart Association, Inc.
Editorials |
Hypoxia, BNip3 Proteins, and the Mitochondrial Death Pathway in Cardiomyocytes
From the Department of Medicine, Johns Hopkins University, Baltimore, Md.
Correspondence to Michael T. Crow, PhD, Johns Hopkins University, Department of Medicine, Division of Pulmonary Medicine, JHAAC, 5501 Hopkins Bayview Cir, Baltimore, MD 21224. E-mail mcrow1@jhmi.edu
Key Words: BNip3/BNip3L/Nix • apoptosis • hypoxia • Bcl-2 proteins • mitochondria permeability transition
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Myocyte cell loss is a prominent and important pathogenic feature of cardiac ischemia. Limiting this loss is a desirable therapeutic goal, but the development of truly effective strategies to achieve that goal requires an understanding of the mechanisms by which ischemia triggers cell death. Investigators have turned to isolated and cultured cardiomyocytes to identify signaling pathways involved in the response to ischemia and to systematically test the effectiveness of prosurvival signaling pathways and various antideath molecules against ischemia-associated cellular insults, such as hypoxia.1–4 Despite some success in this area, it is still not totally clear how hypoxia actually triggers cell death in cardiomyocytes.
One attractive mechanism through which hypoxia might trigger cardiomyocyte cell death is explored by Regula and coworkers5 in this issue of Circulation Research. These investigators present data on the possible role of BNip3, a hypoxia-inducible member of the Bcl-2 family of apoptotic regulators, in mediating cardiomyocyte cell death. They show that (1) BNip3 expression is dramatically increased in response to hypoxia, (2) enforced expression of BNip3 causes cell death in normoxic cardiomyocytes, and (3) enforced expression of a BNip3 mutant lacking its transmembrane domain (BNip3
TM) partially blocks hypoxia-induced cell death. BNip3 is an attractive candidate to play a pivotal role in the cellular response to hypoxia because (1) its expression is regulated by the hypoxia-inducible factor (HIF) transcription complex, the activation of which by hypoxia is a well-characterized response, (2) its activity is tied to the Bcl-2 family of apoptosis regulators, and (3) it is
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