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


RESULTS
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.


CONCLUSIONS
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.
Inotek Pharmaceuticals Corporation, Suite 419E, 100 Cummings Center, Beverly, MA 01915, USA.
Min
M
Chen
Zsuzsanna
Z
Zsengellér
Chun-Yang
CY
Xiao
Csaba
C
Szabó
D000818:Animals; D051033:Apoptosis Inducing Factor; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D005420:Flavoproteins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D011506:Proteins / Q000235:genetics / Q000502:physiology*
D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; C494830:AIFM1 protein, mouse; D011506:Proteins; D045304:Cytochromes c; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases