Cadmium Induces Thymocyte Apoptosis via Caspase‐Dependent and Caspase‐Independent Pathways |
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Authors: | Neelima Pathak Sumonto Mitra Shashi Khandelwal |
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Affiliation: | 1. Department of Pharmaceutical Sciences, Birla Institute of Technology, , Ranchi, 635 215 India;2. CSIR–Indian Institute of Toxicology Research (CSIR‐IITR), , Lucknow, 226 001 India |
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Abstract: | Based on our recent findings that 25 µ M cadmium triggers oxidative stress–mediated caspase‐dependent apoptosis in murine thymocytes, this study is designed to explore whether Cd also induces caspase‐independent apoptosis. We found that pretreatment with caspase inhibitors fails to prevent Cd‐induced apoptosis completely, suggesting the possibility of an additional pathway. Western blot and flow cytometry techniques indicated marked expression of apoptosis‐inducing factor and endonuclease G in nuclear fraction, signifying their translocation from mitochondria to nucleus. Intracellular Ca2+ and reactive oxygen species (ROS) levels significantly raised by Cd were restored by ruthenium red, which had no influence on mitochondrial membrane depolarization and caspase activity and apoptosis. Using cyclosporin A, ROS formation and mitochondrial membrane depolarization were completely abolished, whereas apoptosis was partly attenuated. These results clearly demonstrate more than one apoptotic pathway in thymocytes and support the role of mitochondrial permeability transition pore in the regulation of caspase‐independent cell death triggered by Cd. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:193‐203, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21468 |
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Keywords: | Cadmium Murine Thymocytes Apoptosis Apoptosis‐Inducing factor Endonuclease G Calcium Ruthenium Red Cyclosporine A |
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