2010 Volume 27 Pages 28-34
Tributyltin compound is a toxic organotin compound that produces injury to the central nervous systems of mammals as the main target. In in vitro studies, we examined the effect of tributyltin chloride (TBTC) on RCR-1 cells (a rat astrocytoma cell line). After exposure to 1 μM TBTC, RCR-1 cells induced apoptosis, such as caspase-3 activation, calpain activation and mitochondrial cytochrome c release. TBTC-induced apoptosis was suppressed when RCR-1 cells were pretreated with BAPTA-AM, an intracellular calcium chelator. Furthermore, significant activation of calpain was associated with calcium-dependent enzyme action and an increase of intracellular calcium ([Ca2+]i) was confirmed in TBTC-exposed RCR-1 cells. On the other hand, calpain activation was suppressed by BAPTA-AM, an intracellular calcium chelator. JC-1 assays were used to evaluate mitochondrial function, since a strong expression of cytochrome c by TBTC suggested mitochondrial involvement; cytochrome c release and the loss of mitochondrial function occurred within 10 min of TBTC exposure. These results indicate the presence of a TBTC-induced calcium-dependent apoptotic pathway in RCR-1 cells. In conclusion, the results are thought to contribute greatly to the elucidation of TBTC-induced cell death mechanism of astrocytes and neurons of the central nervous system.
