title: Preconditioning stimulus of proteasome inhibitor enhances aggresome formation and autophagy in differentiated SH-SY5Y cells.
abstract: 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.
authors.affiliation: College of Pharmacy, CHA University, Seongnam, Gyeonggi-do, South Korea; College of Pharmacy, Chonnam National University, Gwangju, South Korea.
authors.forename: Yeojin
authors.initials: Y
authors.lastname: Bang
authors.affiliation: College of Pharmacy, Chonnam National University, Gwangju, South Korea.
authors.forename: Bok Yun
authors.initials: BY
authors.lastname: Kang
authors.affiliation: College of Pharmacy, CHA University, Seongnam, Gyeonggi-do, South Korea. Electronic address: hjchoi3@cha.ac.kr.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D006801:Humans; D002479:Inclusion Bodies / Q000502:physiology* / Q000648:ultrastructure; D007976:Leupeptins / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000494:pharmacology*
chemical_list: D007976:Leupeptins; D061988:Proteasome Inhibitors; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Aggregates; Aggresome; Autophagy; Neurodegenerative disease; Preconditioning; Proteasome inhibitor