Fatty acid-induced apoptosis in neonatal cardiomyocytes: redox signaling.
Exposure of neonatal rat cardiac myocytes to palmitate and glucose produces apoptosis as seen by cytochrome c release, caspase 3-like activation, DNA laddering, and poly(ADP-ribose) polymerase cleavage. The purpose of this study was to understand the role of reactive oxygen species in the initiation of programmed cell death by palmitate. We found that palmitate (but not oleate) produces inhibition of carnitine palmitoyltransferase I, accumulation of ceramide, and inhibition of electron transport complex III. These events are subsequent to cytochrome c release and loss of the mitochondrial membrane potential. No differences in H2O2 production or N-terminal c-Jun kinase phosphorylation were detected between myocytes incubated in palmitate and control myocytes (nonapoptotic) incubated in oleate. These results suggest that the palmitate-induced loss of the mitochondrial membrane potential is not associated with H2O2 synthesis and that a membrane potential is required to generate reactive oxygen species following ceramide inhibition of complex III.
Sparagna
G C
GC
Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Health Science Center, 6431 Fannin, Houston, TX 77030, USA.
Hickson-Bick
D L
DL
Buja
L M
LM
McMillin
J B
JB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D002518:Ceramides / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004247:DNA / Q000032:analysis; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000494:pharmacology; D010084:Oxidation-Reduction; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D002518:Ceramides; D003574:Cytochrome c Group; D004791:Enzyme Inhibitors; D019301:Oleic Acid; D019308:Palmitic Acid; D004247:DNA; D002334:Carnitine O-Palmitoyltransferase; D014450:Electron Transport Complex III