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Oligomycin and antimycin A prevent nitric oxide-induced apoptosis by blocking cytochrome C leakage.
- Source :
-
The Journal of laboratory and clinical medicine [J Lab Clin Med] 2004 Mar; Vol. 143 (3), pp. 143-51. - Publication Year :
- 2004
-
Abstract
- 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 Bax or Bcl-2 proteins, release of cytochrome C from mitochondria into the cytosol, activation of caspase-3, and changes in the mitochondrial membrane potential (DeltaPsi) were measured with the use of Western blotting, c43 lorimetric 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 Bax protein. On the one hand, oligomycin treatment was not accompanied by a decline in DeltaPsi. On the other hand, antimycin A treatment decreased DeltaPsi 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.
- Subjects :
- Adenosine Triphosphate metabolism
Animals
Cell Line
Cytochromes c metabolism
Gastric Mucosa drug effects
Gastric Mucosa physiology
Nitric Oxide pharmacology
Nitrites metabolism
Rats
Antimycin A pharmacology
Apoptosis drug effects
Cytochromes c antagonists & inhibitors
Gastric Mucosa cytology
Nitric Oxide physiology
Nitric Oxide Donors pharmacology
Nitroso Compounds pharmacology
Oligomycins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2143
- Volume :
- 143
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of laboratory and clinical medicine
- Publication Type :
- Academic Journal
- Accession number :
- 15007303
- Full Text :
- https://doi.org/10.1016/j.lab.2003.11.003