TY - JOUR
T1 - Stannin, a protein that localizes to the mitochondria and sensitizes NIH-3T3 cells to trimethyltin and dimethyltin toxicity
AU - Davidson, Collin E.
AU - Reese, Brian E.
AU - Billingsley, Melvin L.
AU - Yun, Jong K.
PY - 2004/10
Y1 - 2004/10
N2 - Stannin (Snn) is a highly conserved, 88-amino acid protein that may mediate the selective toxicity of organotins. Snn is localized in tissues with known sensitivity to trimethyltin (TMT), including the central nervous system, immune system, spleen, kidney and lung. Cells in culture that do not express Snn show considerable resistance to TMT toxicity. In vitro, Snn peptide can bind TMT in a 1:1 ratio and can de-alkylate TMT to dimethyltin (DMT). We now show that transfection with Snn sensitized TMT-resistant NIH-3T3 mouse fibroblasts to both TMT and DMT cytotoxicity. Triple label confocal microscopy of Snn-transfected cells and Percoll gradient purification of mitochondria showed Snn localized to the mitochondria and other membrane structures. The mitochondrial localization of Snn, coupled with its ability to bind and dealkylate organotin compounds, indicates a possible mechanism by which selective alkyltin toxicity might be mediated.
AB - Stannin (Snn) is a highly conserved, 88-amino acid protein that may mediate the selective toxicity of organotins. Snn is localized in tissues with known sensitivity to trimethyltin (TMT), including the central nervous system, immune system, spleen, kidney and lung. Cells in culture that do not express Snn show considerable resistance to TMT toxicity. In vitro, Snn peptide can bind TMT in a 1:1 ratio and can de-alkylate TMT to dimethyltin (DMT). We now show that transfection with Snn sensitized TMT-resistant NIH-3T3 mouse fibroblasts to both TMT and DMT cytotoxicity. Triple label confocal microscopy of Snn-transfected cells and Percoll gradient purification of mitochondria showed Snn localized to the mitochondria and other membrane structures. The mitochondrial localization of Snn, coupled with its ability to bind and dealkylate organotin compounds, indicates a possible mechanism by which selective alkyltin toxicity might be mediated.
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U2 - 10.1124/mol.104.001719
DO - 10.1124/mol.104.001719
M3 - Article
C2 - 15269288
AN - SCOPUS:4844226883
SN - 0026-895X
VL - 66
SP - 855
EP - 863
JO - Molecular pharmacology
JF - Molecular pharmacology
IS - 4
ER -