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

J Neurochem. 1997 Jun;68(6):2493-9. doi: 10.1046/j.1471-4159.1997.68062493.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Nucleus / drug effects
  • DNA Fragmentation / drug effects*
  • DNA, Neoplasm / drug effects*
  • Glioma
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Hybrid Cells / cytology
  • Hybrid Cells / drug effects
  • Hybrid Cells / enzymology
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Neuroblastoma
  • Nitric Oxide / metabolism
  • Nitroprusside / pharmacology
  • Rats
  • Sesquiterpenes / pharmacology
  • Sulfhydryl Reagents / pharmacology

Substances

  • Anti-Bacterial Agents
  • DNA, Neoplasm
  • Sesquiterpenes
  • Sulfhydryl Reagents
  • Nitroprusside
  • Nitric Oxide
  • heptelidic acid
  • L-Lactate Dehydrogenase
  • Glyceraldehyde-3-Phosphate Dehydrogenases