کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859914 | 1133156 | 2015 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The molecular mechanism of rotenone-induced α-synuclein aggregation: Emphasizing the role of the calcium/GSK3β pathway
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کلمات کلیدی
GSK3βLBSPI3KMPTPGSK3DMSO - DMSOα-synuclein - α-سینوکلینPermeability transition pore - افت فشار نفوذ پذیریLewy bodies - بدن لویBAPTA/AM - بیایپیتیای / AMParkinson’s disease - بیماری پارکینسونDimethyl sulfoxide - دیمتیل سولفواکسیدRotenone - روتنونPhosphatidylinositol 3-kinase - فسفاتیدیلینواستیل 3-کینازpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازCalcium - کلسیمglycogen synthase kinase 3 - گلیکوزین سنتاز کیناز 3
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Environmental toxin exposure is associated with the development of Parkinson's disease (PD), and environmental factors can influence the onset of the majority of sporadic PD cases via genetically mediated pathways. Rotenone, a widespread pesticide, induces Parkinsonism and the formation of Lewy bodies in animals; however, the molecular mechanism that underlies α-synuclein aggregation remains unclear. Here, we assessed the aggregation of α-synuclein in PC12 cells with or without cross-linking following rotenone exposure via a variety of methods, including western blotting, immunofluorescence and electron microscopy. We demonstrated that rotenone increased the intracellular calcium levels and induced the aggregation and phosphorylation of α-synuclein in a calcium-dependent manner. Aggregated α-synuclein is typically degraded by autophagy, and rotenone impaired this process. The attenuation of autophagy and α-synuclein alterations were reversed by scavenging calcium. Calcium regulates the activity of AKT-glycogen synthase kinase 3 (GSK3)β. We demonstrated that rotenone attenuated the phosphorylation of AKT and GSK3β, and the elimination of calcium reversed these phenomena. As a GSK3β inhibitor, lithium promoted autophagy and decreased the aggregation and phosphorylation of α-synuclein. GSK3β activation through overexpression depressed autophagy and increased the total protein level and phosphorylation of α-synuclein. These results suggest that rotenone-induced α-synuclein aggregation is mediated by the calcium/GSK3β signaling pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 233, Issue 2, 4 March 2015, Pages 163-171
Journal: Toxicology Letters - Volume 233, Issue 2, 4 March 2015, Pages 163-171
نویسندگان
Yu-he Yuan, Wen-fen Yan, Jian-dong Sun, Ju-yang Huang, Zheng Mu, Nai-Hong Chen,