Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese.
The present findings provide experimental evidence for the hypothesis that an impairment of mitochondrial function may be involved in manganese neurotoxicity. Specifically, the treatment of dopaminergic neuronal-derived cell line (PC12) with MnCl2 produced a significant inhibition of some mitochondrial complexes of the respiratory chain, while in the glial-derived cell line (C6) this effect was not observed. In PC12 the decrease in complex I activity was more pronounce than in other mitochondrial complexes. However treatment of cells with ZnSO4 exerted no significant variations in enzymatic activities. A direct exposure of mitochondrial fraction to MnCl2 reduced enzymatic activities of mitochondria in both cell lines adding further support to the proposed theory that the different sensitivity of the cells to manganese may be explained by a difference in uptake or intracellular storage. These data indicate that manganese neurotoxicity could be the result of a direct effect just on complex I activity or due to a secondary effect of oxidative stress induced by an excess of this transition metal.
Galvani
P
P
Dipartimento di Scienze dell' Ambiente e del Territorio, Facoltà di Scienze, Università degli Studi di Milano, Italy.
Fumagalli
P
P
Santagostino
A
A
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000633:toxicity*; D017895:Manganese Compounds; D020149:Manganese Poisoning; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors*; D009457:Neuroglia / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects; D051381:Rats; D013431:Sulfates / Q000494:pharmacology; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D002712:Chlorides; D017895:Manganese Compounds; D013431:Sulfates; D017967:Zinc Compounds; D019287:Zinc Sulfate; D016660:NAD(P)H Dehydrogenase (Quinone); C025340:manganese chloride