Mitochondrial toxicity of iron and the protective role of ferritin on dopaminergic PC12 cell line.
A specific defect of imtochondrial Complex I activity has recently been identified in the substantia nigra of parkinsonian brain. Using an in vitro dopaminergic PC12 cell line model, a possible pathogenic link has been investigated between this finding and increased levels of iron actually observed in the substantia nigra of parkinsonian patients. Exposure of PC12 cells to FeSO(4) for 168 hr induced a significant inhibition of Complex I, whereas succinate dehydrogenase activity was not reduced by this treatment. Furthermore, the non-dopaminergic cell line (SK-N-BE) was not sensitive to the mitochondria! inhibitory effect of iron. Direct treatment of the mitochondrial fraction with FeSO(4) decreased Complex I activity in both cell lines, suggesting that the difference in sensitivity of cells to iron could be due to the difference in uptake or intracellular storage of this element.
Galvani
P
P
Dipartimento di Scienze dell'Ambiente e del Territorio, Facoltà di Scienze, Università degli Studi di Milano, Italy.
Colleoni
M
M
Origgi
M
M
Santagostino
A
A