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Mechanisms of cell death in oxidant stress and ischemia‐reperfusion injury
Author(s) -
Loor Gabriel,
Kondapalli Jyothi,
Sharma Bumihka,
Guzy Robert,
Schumacker Paul
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a448-c
Subject(s) - menadione , programmed cell death , microbiology and biotechnology , apoptosis , mitochondrion , cytosol , cytochrome c , chemistry , superoxide dismutase , mitochondrial permeability transition pore , fragmentation (computing) , cell , oxidative stress , biology , biochemistry , enzyme , ecology
Cardiomyocyte cell death in ischemia‐reperfusion (I/R) involves the generation of significant oxidant stress, although the cell death pathway is not fully understood. We have examined the critical mediators of oxidant induced cell death in cultured chick cardiomyocytes during simulated I/R, or in response to the redox cycling compound, menadione. Adenoviral overexpression of antioxidant enzymes targeted to different subcellular compartments was used to determine their relative contributions to I/R induced cell death. Catalase overexpression in the cytosol or the mitochondrial matrix provided significant protection against menadione but not against I/R‐induced cell death. By contrast, overexpression of mitochondrial superoxide dismutase (Mn‐SOD) conferred significant protection against I/R injury but not against menadione challenge. Overexpression of anti‐apoptotic Bcl‐X L was not protective against I/R‐ or menadione‐induced cell death, even though cytochrome c release and DNA fragmentation were detected after I/R. In addition, mouse embryonic fibroblasts (MEFs) deficient in Bax and Bak, or overexpressing Bcl‐X L, were not resistant to I/R‐ and menadione‐induced cell death. Thus, mitochondrial oxidant stress is a critical component of I/R‐ induced cell death. This mode of cell death activates but does not require mitochondria‐dependent apoptosis.