Mechanism of nitric oxide-induced apoptosis in human neuroblastoma SH-SY5Y cells

Ryuichi Moriya, Takashi Uehara, Yasuyuki Nomura

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

We have attempted to elucidate the precise mechanism of nitric oxide (NO)-induced apoptotic neuronal cell death. Enzymatic cleavages of DEVD-AFC, VDVAD-AFC, and LEHD-AFC (specific substrates for caspase-3-like protease (caspase-3 and -7), caspase-2, and caspase-9, respectively) were observed by treatment with NO. Western blot analysis showed that pro-forms of caspase-2, -3, -6, and -7 are decreased during apoptosis. Interestingly, Ac-DEVD-CHO, a caspase-3-like protease inhibitor, blocked not only the decreases in caspase-2 and -7, but also the formation of p17 from p20 in caspase-3 induced by NO, suggesting that caspase-3 exists upstream of caspase-2 and -7. Bongkrekic acid, a potent inhibitor of mitochondrial permeability transition, specifically blocked both the loss of mitochondrial membrane potential and subsequent DNA fragmentation in response to NO. Thus, NO results in neuronal apoptosis through the sequential loss of mitochondrial membrane potential, caspase activation, and degradation of inhibitor of caspase-activated DNase (CAD) (CAD activation). Copyright (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalFEBS Letters
Volume484
Issue number3
DOIs
Publication statusPublished - Nov 10 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase
  • Mitochondrion
  • Nitric oxide

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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