Activation of Protein Kinase C by Trimethyltin: Relevance to Neurotoxicity

• DOI: 10.1046/j.1471-4159.1995.65052338.x
• Publication Date: 2010-07-15T23:54:40Z
• Authors: Goran Pavlaković; Michael D. Kane; Charles L. Eyer; Anumantha Kanthasamy; Gary E. Isom
• Keywords: Benzophenanthridines; 0301 basic medicine; 0303 health sciences; Microscopy, Confocal; Cell Death; Trimethyltin Compounds; Blotting, Western; Neurotoxins; Cell Differentiation; Immunohistochemistry; PC12 Cells; Phenanthridines; Rats; Enzyme Activation; 03 medical and health sciences; Alkaloids; Animals; Tissue Distribution; Protein Kinase C

Abstract: The differentiated PC12 cell neuronal model was used to determine the effect of trimethyltin (TMT) on protein kinase C (PKC). Cells treated with 5–20 µM TMT showed a partial and sustained PKC translocation within 30 min and persisted over a 24‐h period. TMT treatment was accompanied by a low level of PKC down‐regulation over 24 h, which was small compared with that produced by phorbol esters. Confocal imaging of differentiated PC12 cells showed that PKC translocates to the plasma membrane and the translocation is blocked by the PKC inhibitor chelerythrine (1 µM). Phorbol myristate‐induced PKC down‐regulation or inhibition with chelerythrine provided protection against TMT‐induced cytotoxicity. It was concluded that TMT‐induced PKC translocation and activation contribute to the cytotoxicity of TMT in differentiated PC12 cells.