Trimethyltin but not triethyltin induces specific neural cell death through the protein stannin

Trimethyltin (TMT) is a neurotoxic organotin compound that induces neurodegeneration in selected areas of the central nervous system. The factors that decide the specificity of TMT toxicity towards different types of cells are still unknown. In vitro exposure of SH-SY5Y cells to TMT, at doses (0.1-5 mu M) similar to those reached after in vivo exposure, is followed by cell death from 1 mu M up to 5 mu M. By contrast, non-neural cells HL 60 cells are affected, and to a lesser extent, only at 5 mu M TMT. Furthermore, nuclear changes typical of apoptosis appeared after treatment with TMT in SH-SY5Y cells, but not in HL 60 cells. Prior treatment of SH-SY5Y cells with an antisense oligonucleotide for stannin, a target protein for TMT, reduced TMT-induced cell death. However, the antisense stannin oligonucleotide did not affect SH-SY5Y cell death induced by triethyltin, another neurotoxic organotin compound, which highlighted the role of stannin in determining TMT toxicity and selectivity. Only Ca2+ chelation due to the pre-incubation of SH-SY5Y cells with 10 mu M BAPTA completely prevented neural cell death at both 1 mu M and 5 mu M TMT.