Analysis of relation between an increase in intracellular calcium and cell death mechanism in RCR-1 cells exposed to tributyltin chloride

Summary Tributyltin compound is a toxic organotin compound that produces injury to the central nervous systems of mam‑ mals as the main target. In in vitro studies we examined the eff ect 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 cal‑ pain 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 signifi cant activation of calpain was associated with calcium‑dependent enzyme action and an increase of intracellular calcium ((Ca2+)i was confi rmed in TBTC‑exposed RCR‑1 cells. On the other hand calpain activation was suppressed by BAPTA‑AM an intracellular cal‑ cium 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.