Premium
Involvement of poly ADP ribosyl polymerase‐1 in acute but not chronic zinc toxicity
Author(s) -
Sheline Christian T.,
Wang Hongmin,
Cai AiLi,
Dawson Valina L.,
Choi Dennis W.
Publication year - 2003
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2003.02865.x
Subject(s) - nad+ kinase , poly adp ribose polymerase , glyceraldehyde 3 phosphate dehydrogenase , neurotoxicity , biology , extracellular , nicotinamide mononucleotide , programmed cell death , microbiology and biotechnology , enzyme , chemistry , biochemistry , polymerase , toxicity , dehydrogenase , nicotinamide adenine dinucleotide , apoptosis , organic chemistry
We have previously suggested that zinc‐induced neuronal death may be mediated in part by inhibition of the glycolytic enzyme glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), secondary to depletion of the essential cosubstrate NAD + . Given convergent evidence implicating the NAD + ‐catabolizing enzyme, poly ADP ribosyl polymerase (PARP) in mediating ATP depletion and neuronal death after excitotoxic and ischemic insults, we tested the specific hypothesis that the neuronal death induced by exposure to toxic levels of extracellular zinc might be partly mediated by PARP. PARP was activated in cultured mouse cortical astrocytes after a toxic acute Zn 2+ exposure (350 µ m Zn 2+ for 15 min), but not in cortical neurons or glia after exposure to a toxic chronic Zn 2+ exposure (40 µ m Zn 2+ for 1–4 h), an exposure sufficient to deplete NAD + and ATP levels. Furthermore, the neurotoxicity induced by acute, but not chronic, Zn 2+ exposure was reduced in mixed neuronal‐glial cultures prepared from mutant mice lacking the PARP gene. These data suggest PARP activation may contribute to more fulminant forms of Zn 2+ ‐induced neuronal death.