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Intracellular GSH levels rather than ROS levels are tightly related to AMA-induced HeLa cell death

Chemico-Biological Interactions, ISSN: 0009-2797, Vol: 171, Issue: 1, Page: 67-78
2008
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Article Description

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 H 2 O 2 and O 2 − 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 Ca 2+ -chelating agent (EGTA/AM) significantly reduced H 2 O 2 levels in AMA-treated HeLa cells. However, treatment with calpain inhibitor III intensified the levels of O 2 − 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.

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