Abstract
Oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease. The molecule, 2,3,5,4′-tetrahydr- oxystilbene-2-O-β-D-glucoside (TSG), is a potent antioxidant derived from the Chinese herb, Polygonum multiflorum Thunb. In this study, we investigated the protective effect of TSG against 6-hydroxydopamine-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. Our data demonstrated that TSG significantly reversed the 6-hydroxydopamine-induced decrease in cell viability, prevented 6-hydroxydopamine-induced changes in condensed nuclei and decreased the percentage of apoptotic cells in a dose-dependent manner. In addition, TSG slowed the accumulation of intracellular reactive oxygen species and nitric oxide, counteracted the overexpression of inducible nitric oxide syntheses as well as neuronal nitric oxide syntheses, and also reduced the level of protein-bound 3-nitrotyrosine. These results demonstrate that the protective effects of TSG on rat adrenal pheochromocytoma PC12 cells are mediated, at least in part, by the ROS-NO pathway. Our results indicate that TSG may be effective in providing protection against neurodegenerative diseases associated with oxidative stress.
Highlights
Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease (AD), is mainly characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) [1,2]
Our study showed that exposure of PC12 cells to 75 mM 6OHDA for 24 h significantly reduced cell viability, induced typical apoptosis features such as nuclei concentration, boosted the percentage of apoptosis cells, increased the level of intracellular reactive oxygen species (ROS) and nitric oxide (NO), induced overexpression of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) and elevated the level of 3-NT
The above changes were markedly reversed in a dose-dependent manner after the pretreatment of PC12 cells with different concentrations of tetrahydr- oxystilbene-2-O-b-D-glucoside (TSG) for 24 h, which suggests that TSG may protect PC12 cells from 6OHDA-induced apoptosis by regulation of ROS-NO pathway
Summary
Parkinson’s disease (PD), the second most common neurodegenerative disorder after Alzheimer’s disease (AD), is mainly characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) [1,2]. The cause of DAergic neuron loss in PD patients remains unexplained. Several lines of evidence in PD patients and animal models have suggested that oxygen-free radicals and oxidative stress are involved in the pathogenesis of PD [3,4,5]. The regulation of oxidative stress may reduce or prevent the loss of DAergic neurons in PD patients. Six-Hydroxydopamine (6-OHDA), a hydroxylated analog of the natural neurotransmitter, dopamine [9], can induce massive oxidative stress leading to the damage of DAergic neurons in vitro and in vivo [10,11,12]. The apoptosis of PC12 cells induced by 6-OHDA has been used as an in vitro experimental model for the study of PD [13,14]
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