Ochratoxin A induces apoptosis in human lymphocytes through down regulation of Bcl-xL

Abstract

Ochratoxin A (OTA) is a widespread mycotoxin contaminating feed and food. Besides its potent nephrotoxicity, OTA also affects the immune system. We demonstrate here a role for Bcl-XL in OTA-induced apoptosis in human lymphocytes. In particular, human peripheral blood lymphocytes and the human lymphoid T cell line, Kit 225 cells, underwent apoptosis in a time- and dose-dependent manner. This apoptosis was inhibited by z-VAD.fmk, suggesting that caspases were responsible for the induction of apoptosis. Moreover, OTA triggered mitochondrial transmembrane potential (Δψm) loss and caspase-9 and caspase-3 activation. Interestingly, Bcl-XL protein expression was decreased by OTA treatment, whereas Bcl-2 protein level was not affected. Down-regulation of bcl-xL mRNA was not observed in cells treated with OTA. Overexpression of Bcl-xL in Kit 225 cells protected them against mitochondrial perturbation and retarded the appearance of apoptotic cells. Taken together, our data indicate that mitochondria are a central component in OTA-induced apoptosis and that the loss of BCl-xL may participate in OTA-induced cell death . © Society of Toxicology 2004; all rights reserved.