It is well known that α-synuclein (αS) plays an important role in the pathogenesis
of Parkinson’s disease (PD). Moreover, oxidative stress is also thought to
be an important factor in PD due to induction of dopaminergic neuronal cell
death by free radicals and enhancement of αS fibrillation by oxidized stress. In
the present study, to clarify the role of glutathione (GSH), an intracellular antioxidant,
on the molecular mechanism of αS-induced cell injury, we examined
the effects of L-buthionine-SR-sulfoximine (BSO), a GSH synthase
inhibitor, with or without N-acetyl-L-cysteine (NAC), a source of GSH, on
αS-induced cell injury in human neuroblastoma SH-SY5Y cells. Treatment with
BSO significantly reduced the cell viability of both empty-vector- and αS-transfected
SH-SY5Y cells in a dose-dependent manner (p < 0.01), although the ratio
of αS-induced reduction of cell viability in α-syn-transfected cells was much
greater than that in empty-vector-transfected cells. Moreover, BSO significantly
reduced the intracellular total GSH level in both types of transformant cells.
However, NAC significantly prevented BSO-induced reduction of both cell viability
and GSH level in the αS-transfected cells. These findings suggest that GSH
plays an important role in αS-induced cell injury by reducing cell viability.
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