Critical role of calcium overloading in cadmium-induced apoptosis in mousethymocytes

Cadmium (Cd) is a well-known environmental carcinogen and immunotoxin, Curr ently the direct cytotoxic effects of Cd on thymocytes are largely unexplor ed. The main objective of the present study was to investigate the apoptoge nic property of Cd and the mechanisms involved, using primary cultured mous e thymocytes as a model. Cd-induced apoptosis in thymocytes was studied by TdT-mediated dUTP nick end-labeling assay and DNA gel electrophoresis. The results showed that Cd was able to cause apoptosis in mouse thymocytes in a time- and dose-dependent manner. Moreover, Cd exposure led to a rapid and sustained intracellular calcium (Ca2+) elevation, followed by caspase-3 act ivation and PARR cleavage, all of which preceded the characteristic DNA fra gmentation. BAPTA-AM, a specific intracellular Ca2+ chelator, abolished Cd- induced Ca2+ overloading and subsequently inhibited caspase-3 activation, P ARP cleavage, and apoptosis. It is believed that intracellular Ca2+ elevati on may trigger caspase-3 activation either through mitochondria or through activation of Ca2+-dependent protease in Cd-treated thymocytes. Results fro m this study thus provide new information for a better understanding of the immunotoxic and immunomodulatory effects of Cd, (C) 2001 Academic Press.