INVOLVEMENT OF TUBULIN IN MPP(+) NEUROTOXICITY ON NGF-DIFFERENTIATED PC12 CELLS

In vivo, the neurotoxin MPTP is oxidated to MPP(+), which is toxic to dopaminergic neurons. In this paper, we have used MPP(+) as a tool to evoke neurotoxicity in the PC12 cell line and investigate the intracellular events that are involved. A cytotoxicity test, performed on undifferentiated and NGF-differentiated PC12 cells, showed that MPP(+) is much more toxic on differentiated cells and indicated the suitable range of concentrations for studying the starting events evoked by the neurotoxin. By indirect immunofluorescence we have shown that the localisation of alpha - and beta -tubulin in NGF-differentiated cells was modified by a 24 h treatment with 15 mu mol/l MPP(+). A biochemical analysis was performed on cell extracts and the results showed that MPP(+) treatment induced an increase in alpha -tubulin levels and a decrease in beta -tubulin levels. These results suggest the involvement of the two microtubule proteins in MPP(+) neurotoxicity on NGF-differentiated PC12 cells.