Koningic acid (a potent glyceraldehyde-3-phosphate dehydrogenase inhibitor)-induced fragmentation and condensation of DNA in NG108-15 cells

Minako Nakazawa, Takashi Uehara, Yasuyuki Nomura

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2493-2499
Number of pages7
JournalJournal of Neurochemistry
Volume68
Issue number6
DOIs
Publication statusPublished - Jun 1997

Keywords

  • Apoptosis
  • Glyceraldehyde-3-phosphate dehydrogenase
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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