title: 14-3-3 Proteins in the regulation of rotenone-induced neurotoxicity might be via its isoform 14-3-3epsilon's involvement in autophagy.
abstract: 14-3-3 proteins have been confirmed to be involved in Parkinson's disease. It has been reported that an increase of 14-3-3 (theta, epsilon, and gamma) expression has neuroprotective effect in response to rotenone and MPP(+) in dopaminergic cell culture and transgenic C. elegans with alpha-synuclein overexpression. To further investigate the detail mechanism of 14-3-3 proteins in rotenone-induced dopamine neurotoxicity, we observed the expression of 14-3-3 isoforms, and the influence of 14-3-3epsilon knockdown on autophagic activity and cell function. The results showed that rotenone led to a decrease in expression of 14-3-3 protein and mRNA, and an increase in expression and aggregation of alpha-synuclein protein. Knockdown of 14-3-3epsilon expression in turn further aggravated PC12 cell damage, such as an enhancement of ROS formation, and a reduction of cell viability and ATP production. Further experiments confirmed that the autophagic activity was promoted with 14-3-3epsilon siRNA transfection, including an enhancement of autophagosome formation and the ratio of LC3-II/LC3-I. Therefore, we concluded that the regulation of 14-3-3 proteins in rotenone-induced neurotoxicity might be associated with its isoform 14-3-3epsilon's involvement in autophagy, which might be considered a mechanism in addition to the currently known function of 14-3-3 proteins in neurodegenerative disease pathogenesis.
authors.affiliation: The Institute of Toxicology, Third Military Medical University, Chongqing, 400038, China, ys2000cn@hotmail.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sai
authors.forename: Kaige
authors.initials: K
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuanpeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Dong
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000633:toxicity*; D014162:Transfection; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D000255:Adenosine Triphosphate; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012402:Rotenone; D051844:alpha-Synuclein; C526109:Anxa3 protein, rat