NO DEPLETES CELLULAR ATP CONTENTS VIA INACTIVATION OF GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE IN PC12 CELLS

Abstract

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 nitro-prusside (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 effedct 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.