Abstract
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.
Highlights
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
We examined the effects of L-buthionine-SR-sulfoximine (BSO), a typical GSH synthase inhibitor, with or without N-acetylcysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells, to clarify the role of GSH on the molecular mechanism of αS-induced cell injury
BSO induced a reduction of cell viability in αS-transfected SH-SY5Y cells; in particular, treatment with BSO (100 μM) for 144 h resulted in markedly reduced cell viability in αS-transfected cells compared with the control cells (Figure 2; p < 0.01)
Summary
This pathology is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of cytoplasmic inclusions known as Lewy bodies (LB) [1]. Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatic oxidation [4] or auto-oxidation of an excess amount of dopamine (DA) [5], is thought to play an important role in dopaminergic (DAergic) neurotoxicity [6]. We examined the effects of L-buthionine-SR-sulfoximine (BSO), a typical GSH synthase inhibitor, with or without N-acetylcysteine (NAC), a source of GSH, on αS-induced cell injury in human neuroblastoma SH-SY5Y cells, to clarify the role of GSH on the molecular mechanism of αS-induced cell injury
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