ToxSci Advance Access published online on March 31, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh123
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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1 INSERM UMR-S 461, Faculté de Pharmacie Paris XI, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France; Laboratoire de Toxicologie, Faculté de Pharmacie, Université Saint-Joseph, Beirut, Lebanon
* To whom correspondence should be addressed. E-mail: marc.pallardy{at}cep.u-psud.fr.
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 (
© 2004 Toxicological Sciences © Society of Toxicology 2004; all rights reserved.
Immunotoxicology
Ochratoxin A Induces Apoptosis in Human Lymphocytes through Downregulation of Bcl-xL
2 Laboratoire de Toxicologie, Faculté de Pharmacie, Université Saint-Joseph, Beirut, Lebanon
3 INSERM UMR-S 461, Faculté de Pharmacie Paris XI, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France
Abstract 
m) 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. Downregulation 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.
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