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

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

Toxicol Sci

INSERM UMR-S 461, Faculté de Pharmacie Paris XI, 5 rue J.-B. Clément, 92296 Châtenay-Malabry Cedex, France.

Published: June 2004

AI Article Synopsis

Article 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-x(L) 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 (Deltachim) loss and caspase-9 and caspase-3 activation. Interestingly, Bcl-x(L) protein expression was decreased by OTA treatment, whereas Bcl-2 protein level was not affected. Down-regulation of bcl-x(L) mRNA was not observed in cells treated with OTA. Overexpression of Bcl-x(L) 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-x(L) may participate in OTA-induced cell death.

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http://dx.doi.org/10.1093/toxsci/kfh123DOI Listing

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