Stannin, a protein that localizes to the mitochondria and sensitizes NIH-3T3 cells to trimethyltin and dimethyltin toxicity.
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.
Department of Pharmacology, 500 University Dr., Pennsylvania State College of Medicine, Hershey 17033, USA.
Collin E
CE
Davidson
Brian E
BE
Reese
Melvin L
ML
Billingsley
Jong K
JK
Yun
D000818:Animals; D020169:Caspases / Q000378:metabolism; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D009947:Organotin Compounds / Q000494:pharmacology*; D013347:Subcellular Fractions; D014162:Transfection; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D009479:Neuropeptides; D009947:Organotin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; C039760:dimethyltin; C075692:stannin; D020169:Caspases