"Biphasic Dose-Response of Mn-Induced Mitochondrial Damage, PINK1/Parkin Expression, and Mitophagy in SK-N-SH Cells"

作者全名："Zhang, Yue; Hu, Hong-Tao; Cao, Yu-Min; Jiang, Zhi-Gang; Liu, Jie; Fan, Qi-Yuan"

作者地址："[Zhang, Yue] Hosp Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Dept Pediat, Chongqing, Peoples R China; [Zhang, Yue; Hu, Hong-Tao; Jiang, Zhi-Gang; Fan, Qi-Yuan] Zunyi Med Univ, Sch Publ Hlth, Zunyi, Peoples R China; [Cao, Yu-Min] Zunyi Med Univ, Afliated Hosp 3, Peoples Hosp Zunyi 1, Zunyi, Peoples R China; [Liu, Jie] Zunyi Med Univ, Key Lab Basic Pharmacol, Minist Educ, Zunyi, Peoples R China; [Fan, Qi-Yuan] Zunyi Med & Pharmaceut Coll, Zunyi, Peoples R China; [Liu, Jie] Zunyi Med Univ, Dept Pharmacol, 5 Xingpu Rd, Zunyi 563003, Peoples R China"

通信作者："Fan, QY (通讯作者)，Zunyi Med Univ, Sch Publ Hlth, Zunyi, Peoples R China.; Liu, J (通讯作者)，Zunyi Med Univ, Dept Pharmacol, 5 Xingpu Rd, Zunyi 563003, Peoples R China."

来源：DOSE-RESPONSE

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000976168200001

JCR分区：Q2

影响因子：2.3

年份：2023

卷号：21

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：manganese (Mn); SK-N-SH cells; mitochondria damage; PINK1/parkin; biphasic mitophagy; cell death

摘要："Excessive manganese (Mn) exposure produces neurotoxicity with mitochondrial damage. Mitophagy is a protective mechanism to eliminate damaged mitochondria to protect cells. The aim of this study was to determine the dose-response of Mn-induced mitochondria damage, the expression of mitophagy-mediated protein PINK1/Parkin and mitophagy in dopamine-producing SKN-SH cells. Cells were exposed to 0, 300, 900, and 1500 mu M Mn2+ for 24 h, and ROS production, mitochondrial damage and mitophagy were examined. The levels of dopamine were detected by ELISA and neurotoxicity and mitophagy-related proteins (alpha-synuclein, PINK1, Parkin, Optineurin, and LC3II/I) were detected by western blot. Mn increased intracellular ROS and apoptosis and decreased mitochondrial membrane potential in a concentration-dependent manner. However, at the low dose of 300 mu M Mn, autophagosome was increased 11-fold, but at the high dose of 1500 mu M, autophagosome was attenuated to 4 fold, together with decreased mitophagy-mediated protein PINK1/Parkin and LC3II/I ratio and increased Optineurin expression, resulting in increased alpha-synuclein accumulation and decreased dopamine production. Thus, Mn-induced mitophagy exhibited a novel biphasic regulation: at the low dose, mitophagy is activated to eliminate damaged mitochondria, however, at the high dose, cells gradually loss the adaptive machinery, the PINK1/Parkin-mediated mitophagy weakened, resulting in neurotoxicity."

基金机构：National Natural Science Foundation of China [81860568]

基金资助正文："The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by National Natural Science Foundation of China (81860568)."