NADH can enter into astrocytes and block poly(ADP-ribose) polymerase-1-mediated astrocyte death.
Poly(ADP-ribose) polymerase-1 consumes NAD to catalyze poly(ADP-ribosyl)ation of target proteins, which modulates various biological functions. However, excessive poly(ADP-ribose) polymerase-1 activation mediates oxidative cell death. Our recent studies have indicated that NAD can enter into astrocytes to prevent poly(ADP-ribose) polymerase-1 cytotoxicity. In this study, we show that NADH can also enter into astrocytes, which can significantly decrease poly(ADP-ribose) polymerase-1-induced astrocyte death even when applied 3-4 h after poly(ADP-ribose) polymerase-1 activation. The protective effects can be produced by 10 muM NADH, which is significantly lower than that required for NAD to be protective. These results provide novel information suggesting that NADH can be used for decreasing poly(ADP-ribose) polymerase-1 toxicity, and extracellular NADH can enter into astrocytes to influence cellular functions.
Zhu
Keqing
K
Department of Neurology, University of California at San Francisco and Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA.
Swanson
Raymond A
RA
Ying
Weihai
W
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D009243:NAD / Q000378:metabolism / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D008769:Methylnitronitrosoguanidine; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases