Nicotinamide as a precursor for NAD+ prevents apoptosis in the mouse brain induced by tertiary-butylhydroperoxide.
The vitamin nicotinamide can protect against oxidative stress-induced apoptosis in the brain when used as a precursor for nicotinamide adenine dinucleotide (NAD+). The intracerebroventricular administration of tertiary-butylhydroperoxide (t-buOOH) to mice was used to simulate physiologic oxidative stress and apoptosis which may occur in some neurodegenerative conditions. t-buOOH produced characteristic apoptotic nuclear degeneration in neurons with extensive fragmentation of DNA. In this report we show that the elevation of NAD+ by nicotinamide prevents DNA fragmentation during apoptosis or necrosis in the brain as stimulated by t-buOOH administration. NAD+ levels can be increased by 50% in the brain. This may prevent the critical depletion of NAD+ by poly(ADP-ribose) polymerase (PARP) and provide additional substrate during the repair of DNA. Nicotinamide may be of particular interest in the treatment of neurodegeneration.
Klaidman
L K
LK
Department of Molecular Pharmacology and Toxicology, University of Southern California, School of Pharmacy 90033, USA.
Mukherjee
S K
SK
Hutchin
T P
TP
Adams
J D
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D009243:NAD / Q000378:metabolism*; D009410:Nerve Degeneration / Q000187:drug effects; D009536:Niacinamide / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress; D010545:Peroxides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D009243:NAD; D009536:Niacinamide; D004247:DNA; D020122:tert-Butylhydroperoxide; D011065:Poly(ADP-ribose) Polymerases