title: Cadmium induces thymocyte apoptosis via caspase-dependent and caspase-independent pathways.
abstract: Based on our recent findings that 25 µM 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.
authors: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, 635 215, India.
authors: Neelima
authors: N
authors: Pathak
authors: Sumonto
authors: S
authors: Mitra
authors: Shashi
authors: S
authors: Khandelwal
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology* / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004706:Endodeoxyribonucleases / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D060168:Thymocytes / Q000187:drug effects*
chemical_list: D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D017382:Reactive Oxygen Species; D002104:Cadmium; D016572:Cyclosporine; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; D002118:Calcium