Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 171, Issue 1, Pages 67-78Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2007.08.011
Keywords
antimycin A; ROS; apoptosis; HeLa; ROS scavenger; GSH
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Antimycin A (AMA) inhibits succinate oxidase and NADH oxidase, and also inhibits mitochondrial electron transport between cytochromes b and c. We investigated the involvement of ROS and GSH in AMA-induced HeLa cell death. AMA increased the intracellular H2O2 and O-2(center dot-) levels and reduced the intracellular GSH content. ROS scavengers (Tempol, Tiron, Trimetazidine and NAC) did not down-regulate the production of ROS and inhibit apoptosis in AMA-treated cells. Treatment with NAC and N-propylgallate showing the enhancement of GSH depletion in AMA-treated cells significantly intensified the levels of apoptosis. Calpain inhibitors I and II (calpain inhibitor III) and Ca2+ -chelating agent (EGTA/AM) significantly reduced H2O2 levels in AMA-treated HeLa cells. However, treatment with calpain inhibitor III intensified the levels of O-2(center dot-) in AMA-treated cells. In addition, calpain inhibitor III strongly depleted GSH content with an enhancement of apoptosis in AMA-treated cells. Conclusively, the changes of ROS by AMA were not tightly correlated with apoptosis in HeLa cells. However, intracellular GSH levels are tightly related to AMA-induced cell death. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
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