Activation of protein kinase C by trimethyltin: relevance to neurotoxicity.
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 microM 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 microM). 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.
Pavlaković
G
G
Department of Pharmacology and Toxicology, Purdue University, West Lafayette, IN 47907-1334, USA.
Kane
M D
MD
Eyer
C L
CL
Kanthasamy
A
A
Isom
G E
GE
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D015153:Blotting, Western; D016923:Cell Death; D002454:Cell Differentiation; D004789:Enzyme Activation; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009498:Neurotoxins / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D014018:Tissue Distribution; D014298:Trimethyltin Compounds / Q000494:pharmacology*
D000470:Alkaloids; D053119:Benzophenanthridines; D009498:Neurotoxins; D010617:Phenanthridines; D014298:Trimethyltin Compounds; C046488:trimethyltin; C016299:chelerythrine; D011493:Protein Kinase C