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 mangan ese neurotoxicity. Specifically, the treatment of dopaminergic neurona l-derived cell line (PC12) with MnCl2 produced a significant inhibitio n of some mitochondrial complexes of the respiratory chain, while in t he glial-derived cell line (C6) this effect was not observed. In PC12 the decrease in complex I activity was more pronounced than in other m itochondrial complexes. However treatment of cells with ZnSO4 exerted no significant variations in enzymatic activities. A direct exposure o f mitochondrial fraction to MnCl2 reduced enzymatic activities of mito chondria in both cell lines adding further support to the proposed the ory that the different sensitivity of the cells to manganese may be ex plained 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 oxi dative stress induced by an excess of this transition metal.