PMID- 9166744 OWN - NLM STAT- MEDLINE DCOM- 19970617 LR - 20190630 IS - 0022-3042 (Print) IS - 0022-3042 (Linking) VI - 68 IP - 6 DP - 1997 Jun TI - Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase inhibitor)-induced fragmentation and condensation of DNA in NG108-15 cells. PG - 2493-9 AB - We examined nitric oxide (NO)-induced cell death in NG108-15 cells using NO donors. Both sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine caused lactate dehydrogenase (LDH) leakage from NG108-15 cells. NO is known to increase the amount of radioisotopic labeled glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in the presence of [32P]NAD and to inhibit the enzyme activity. To clarify the relationship between the NO-induced inhibition of GAPDH activity and cell death, we studied the effect of koningic acid (KA), a potent selective inhibitor of GAPDH. Both SNP and KA elicited LDH leakage, chromosomal condensation, and fragmentation of nuclei in NG108-15 cells. Gel electrophoretic analysis of cellular DNA extracted from SNP- and KA-treated cells revealed the internucleosomal DNA fragmentation typical of apoptosis in these cultures. The results suggested that in NG108-15 cells, (a) the inhibition of GAPDH activity results in apoptosis and (b) SNP-induced cell death is partly due to the NO-induced inhibition of GAPDH, perhaps by stimulating the binding of NAD to GAPDH. FAU - Nakazawa, M AU - Nakazawa M AD - Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. FAU - Uehara, T AU - Uehara T FAU - Nomura, Y AU - Nomura Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Anti-Bacterial Agents) RN - 0 (DNA, Neoplasm) RN - 0 (Sesquiterpenes) RN - 0 (Sulfhydryl Reagents) RN - 169D1260KM (Nitroprusside) RN - 31C4KY9ESH (Nitric Oxide) RN - 57710-57-3 (heptelidic acid) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases) SB - IM MH - Animals MH - Anti-Bacterial Agents/*pharmacology MH - Apoptosis/drug effects MH - Cell Nucleus/drug effects MH - DNA Fragmentation/*drug effects MH - DNA, Neoplasm/*drug effects MH - Glioma MH - Glyceraldehyde-3-Phosphate Dehydrogenases/antagonists & inhibitors/metabolism MH - Hybrid Cells/cytology/drug effects/enzymology MH - L-Lactate Dehydrogenase/metabolism MH - Mice MH - Neuroblastoma MH - Nitric Oxide/metabolism MH - Nitroprusside/pharmacology MH - Rats MH - Sesquiterpenes/pharmacology MH - Sulfhydryl Reagents/pharmacology EDAT- 1997/06/01 00:00 MHDA- 1997/06/01 00:01 CRDT- 1997/06/01 00:00 PHST- 1997/06/01 00:00 [pubmed] PHST- 1997/06/01 00:01 [medline] PHST- 1997/06/01 00:00 [entrez] AID - 10.1046/j.1471-4159.1997.68062493.x [doi] PST - ppublish SO - J Neurochem. 1997 Jun;68(6):2493-9. doi: 10.1046/j.1471-4159.1997.68062493.x.