کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4338678 | 1614877 | 2011 | 11 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y](/preview/png/4338678.png)
Recent studies have shown that autophagy upregulation may be a tractable therapeutic intervention for clearing the disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in Parkinson's disease (PD). In this study, we explored a novel pharmacotherapeutic approach to treating PD by utilizing potential autophagy enhancers valproic acid (VPA) and carbamazepine (CBZ). Pretreatment with VPA (3 mM) and CBZ (50 μM) along with positive control rapamycin (Rap, 0.2 μM) or lithium (LiCl, 10 mM) significantly enhanced cell viability, decreased rotenone-induced nuclear fragmentation and apoptosis, ameliorated the decrease in mitochondrial membrane potential, reduced reactive oxygen species generation in the human neuroblastoma SH-SY5Y cells. Specifically, the numbers of lysosomes and autophagic vacuolar organelles were increased and the microtubule-associated protein 1 light chain 3-II (LC3-II) expression was up-regulated by VPA, CBZ, Rap, and LiCl (53%, 31%, 72%, and 63%), suggesting that these agents activated autophagic pathways. Moreover, pretreatment with the autophagy inhibitor chloroquine (Chl, 10 μM) remarkably strengthened rotenone toxicity in these cells. Our results suggest that VPA and CBZ, the most commonly used anti-epilepsy and mood-stabilizing medications with low-risk and easy administration might be potential therapeutics for PD.
▶In SH-SY5Y cells, ▶VPA and CBZ improved cell viability against rotenone toxicity. ▶VPA and CBZ ameliorated rotenone-induced MPP reduction, ROS generation and apoptosis. ▶The autophagy inhibitor Chl reinforced rotenone toxicity. ▶VPA and CBA up-regulated LC3-II expression and the numbers of lysosomes. ▶VPA and CBA increased autophagic vacuolar organelle formation.
Journal: Neuroscience - Volume 199, 29 December 2011, Pages 292–302