Cyclosporin A inhibits oxidant and calcium stimulated phospholipase D activity in the rat intestinal mitochondria.

Mitochondrial swelling and calcium cycling occurs during oxidative stress and can be prevented by cyclosporin A (CysA). Our earlier work has shown that enterocyte mitochondria contains a phospholipase D (PLD) which can be activated by superoxide or calcium. In this study, we have shown that enterocyte mitochondrial PLD activated by these agents can be inhibited by cyclosporin A. This was clearly shown by the absence of phosphatidic acid (PA) formation and phosphatidylethanolamine (PE) degradation. Since this PLD specifically utilizes PE as substrate, PLD activity was also assessed by ethanolamine formation which was inhibited by CysA. CysA also inhibited the cabbage PLD activity as judged by phosphatidylethanol formation. These results suggest that cyclosporin A is an inhibitor of PLD and this may be one of the mechanism by which CysA protects enterocyte mitochondria from oxidative stress.