Mitochondrial-to-nuclear translocation of apoptosis-inducing factor in cardiac myocytes during oxidant stress: potential role of poly(ADP-ribose) polymerase-1

Oxidant stress-induced activation of poly(ADP-ribose) polymerase (PARP) plays a role in the pathogenesis of various cardiovascular diseases. We have now investigated the role of PARP in the death of cardiac myocytes in response to oxidant stress induced by hydrogen peroxide, with focus on the mitoch...

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Bibliographic Details
Published in:Cardiovascular research 2004-09, Vol.63 (4), p.682-688
Main Authors: MIN CHEN, ZSENGELLER, Zsuzsanna, XIAO, Chun-Yang, SZABO, Csaba
Format: Article
Language:English
Subjects:
Animals
Apoptosis Inducing Factor
Biological and medical sciences
Biological Transport
Cardiology. Vascular system
Cell Nucleus - metabolism
Cells, Cultured
Cytochromes c - metabolism
Flavoproteins - analysis
Flavoproteins - metabolism
Male
Medical sciences
Membrane Potentials
Membrane Proteins - analysis
Membrane Proteins - metabolism
Mice
Mice, Knockout
Mitochondria, Heart - metabolism
Myocytes, Cardiac - metabolism
Oxidative Stress
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Proteins - genetics
Proteins - physiology
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Summary:Oxidant stress-induced activation of poly(ADP-ribose) polymerase (PARP) plays a role in the pathogenesis of various cardiovascular diseases. We have now investigated the role of PARP in the death of cardiac myocytes in response to oxidant stress induced by hydrogen peroxide, with focus on the mitochondrial function. Using wild-type and PARP-1-deficient murine myocytes challenged with hydrogen peroxide, we found that mitochondrial respiration and mitochondrial membrane potential were better preserved in PARP-deficient myocytes and cellular NAD+ levels were maintained. The release of the mitochondrial cell death factor cytochrome c, and the mitochondrial-to-nuclear translocation of apoptosis-inducing factor (AIF) were also attenuated in the PARP-deficient myocytes. PARP-1, directly or indirectly, regulates the translocation of AIF in myocytes subjected to oxidative stress. The current results are consistent with the view that PARP-1 activation, via induction of mitochondrial dysfunction and promotion of mitochondrial cell death pathways, plays a deleterious pathophysiological role under conditions of oxidative stress.
ISSN:0008-6363
1755-3245
DOI:10.1016/j.cardiores.2004.04.018