Oligomycin and antimycin A prevent nitric oxide-induced apoptosis by blocking cytochrome C leakage

Naohiro Dairaku, Katsuaki Kato, Kennichi Honda, Tomoyuki Koike, Katsunori Iijima, Akira Imatani, Hitoshi Sekine, Shuichi Ohara, Hiroshi Matsui, Tooru Shimosegawa

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17 Citations (Scopus)


Nitric oxide (NO) is a potent inducer of apoptosis, and its cytotoxicity is closely related to mitochondrial dysfunction. In this study we investigated the effects of a F0F1-ATPase inhibitor, oligomycin, and a mitochondrial respiratory chain complex III inhibitor, antimycin A, on NO-induced apoptosis. We used a normal rat gastric-epithelium cell line, RGM-1, treated with a pure NO donor, NOC-1 - 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene - in the presence or absence of oligomycin or antimycin A. Changes in the expressions of Box or Bcl-2 proteins, release of cytochrome C from mitochondria into the cytosol, activation of caspase-3, and changes in the mitochondrial membrane potential (ΔΨ) were measured with the use of Western blotting, colorimetric assays, and a mitochondrial potential sensor, JC-1 dye. Treatment with NOC-18 induced dose-dependent apoptotic cell death in RGM-1 cells. Cell death was accompanied by mitochondrial depolarization, increases in Bax protein expression and cytochrome C leakage, and, subsequently, caspase-3 activation. Oligomycin and antimycin A prevented NO-induced apoptosis in a dose-dependent fashion by preventing cytochrome C release independent of Bcl-2 expression. However, neither compound affected the up-regulation of Box protein. On the one hand, oligomycin treatment was not accompanied by a decline in ΔΨ. On the other hand, antimycin A treatment decreased ΔΨ regardless of NOC-18 treatment. The findings of this study suggest that various functional molecules that constitute the mitochondrial respiratory chain may contribute to cytochrome C release that occurs during NO-induced apoptosis.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalJournal of Laboratory and Clinical Medicine
Issue number3
Publication statusPublished - 2004 Mar

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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