Document Detail

NO depletes cellular ATP contents via inactivation of glyceraldehyde-3-phosphate dehydrogenase in PC12 cells.
MedLine Citation:
PMID:  9922941     Owner:  NLM     Status:  MEDLINE    
Recently, we demonstrated that nitric oxide (NO) reduces ATP generation via oxidative phosphorylation coupled with the mitochondrial respiratory chain in PC12 cells resulting in induction of apoptotic cell death. To further study the correlation between NO-induced ATP depletion and neuronal death, we examined the effect of NO on glycolytic ATP generation in PC12 cells, a neuronal model. When the oxidative phosphorylation was maximally suppressed by DNP and oligomycin, which are inhibitors of the mitochondrial respiratory chain, the cellular ATP contents were reduced by sodium nitroprusside (SNP). In addition, the cellular ATP contents were further decreased along with a decrease in the activity of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a key enzyme in the glycolytic pathway. Benzamide, an inhibitor of poly (ADP-ribose) synthetase, could protect the depletion of NAD but had no effect on the depletion of ATP in PC12 cells induced by NO. These results suggest that the depletion of ATP in PC12 cells caused via the inhibition of G3PDH by NO is one of the mechanisms responsible for NO neurotoxicity.
M Yasuda; H Fujimori; H Panhou
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of toxicological sciences     Volume:  23     ISSN:  0388-1350     ISO Abbreviation:  J Toxicol Sci     Publication Date:  1998 Dec 
Date Detail:
Created Date:  1999-04-14     Completed Date:  1999-04-14     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7805798     Medline TA:  J Toxicol Sci     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  389-94     Citation Subset:  IM    
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
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MeSH Terms
Adenosine Triphosphate / analysis*
Benzamides / pharmacology
Cell Respiration / drug effects
Dinitrophenols / pharmacology
Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors*
Nitric Oxide / toxicity*
Nitroprusside / pharmacology
Oligomycins / pharmacology
Oxidative Phosphorylation / drug effects
PC12 Cells
Poly(ADP-ribose) Polymerases / antagonists & inhibitors
Reg. No./Substance:
0/Benzamides; 0/Dinitrophenols; 0/Oligomycins; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 27208-38-4/benzamide; 56-65-5/Adenosine Triphosphate; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases; EC Polymerases

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