Preconditioning stimulus of proteasome inhibitor enhances aggresome formation and autophagy in differentiated SH-SY5Y cells

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• 作者：Yeojin Bang^a ; ^b ; Bok Yun Kang^b ; Hyun Jin Choi^a ; ^{hjchoi3@cha.ac.kr" class="auth_mail}
• 关键词：PD ; Parkinson's disease ; UPS ; ubiquitin-proteasome system.
• 刊名：Neuroscience Letters
• 出版年：30 April, 2014
• 年：2014
• 卷：566
• 期：Complete
• 页码：263-268
• 全文大小：1788 K

文摘

The abnormal accumulation of protein aggregates is a dominant pathological feature common in neurodegenerative diseases. Autophagy contributes to the processing of aggregated proteins resistant to proteasomal degradation. Autophagic degradation is multi-step process, and especially aggresome formation is a specific and active cellular process for appropriate autophagy-mediated protein homeostasis mechanism. Here, we showed that preconditioning of cells with a non-toxic low dose of MG132 induced autophagy, using an in vitro experimental model that closely represents the characteristics of the autophagy pathway under proteasome inhibition. Clear and large aggresome-like protein accumulation was observed in the perinuclear region of differentiated SH-SY5Y cells with preconditioning stimulus. This results in up-regulation of autophagosome formation and turnover and degradation of intracellular ubiquitinated and p62-bound protein aggregates. Pretreatment with low dose of MG132 attenuated proteinopathy-related cytotoxicity. Together, our experimental model could provide a proper in vitro system for studying the autophagy-related pathophysiology of neurodegeneration, especially therapeutic targeting of intracellular aggresome-like aggregates formation.