کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
8553510 1562589 2018 11 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
6-Hydroxydopamine induces autophagic flux dysfunction by impairing transcription factor EB activation and lysosomal function in dopaminergic neurons and SH-SY5Y cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
6-Hydroxydopamine induces autophagic flux dysfunction by impairing transcription factor EB activation and lysosomal function in dopaminergic neurons and SH-SY5Y cells
چکیده انگلیسی
Autophagy deregulation has been implicated in Parkinson's disease (PD), yet the role of autophagy in neuronal survival remains controversial. In this study, we comprehensively investigated the time-course of autophagy-related markers in 6-OHDA-induced Parkinsonian rat models and assessed its effect on the state of autophagic flux both in vivo and in vitro. We observed an early activation of autophagy followed by autophagic flux impairment, which was confirmed with autophagy inhibitor chloroquine in vivo and Ad-GFP-mCherry-LC3-infected SH-SY5Y cells in vitro. In addition, 6-OHDA not only remarkably reduced the expression level of lysosome-associated membrane protein 1 (Lamp1), but also impaired the hydrolase activities of lysosomal proteases. Transcription factor EB (TFEB), a key transcription factor controlling lysosome biogenesis, was also significantly downregulated by 6-OHDA and its nuclear translocation was inhibited as well, which could account for the impaired lysosomal function. Promoting lysosome biogenesis through TFEB overexpression could protect SH-SY5Y cells against 6-OHDA-induced neurotoxicity. The above findings demonstrated that autophagic flux dysfunction was closely associated with 6-OHDA-induced neurotoxicity and highlighted the importance of functional lysosomes and homeostatic autophagic flux in developing therapeutic agents for PD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 283, February 2018, Pages 58-68
نویسندگان
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