title: Mitochondrial proteomic alterations caused by long-term low-dose copper exposure in mouse cortex.
abstract: Mitochondrial dysfunction is involved in neurotoxicity caused by exposure of various chemicals such as copper. However, the effects of long-term low-dose copper exposure on mitochondrial proteome remain unclear. In this study, we found the treatment of copper (0.13ppm copper sulfate in drinking water) for 12 months caused abnormal expression of a total of 13 mitochondrial proteins (7 up-regulated and 6 down-regulated) as revealed by two-dimensional electrophoresis coupled with mass spectrometry in mouse cortex. Protein functional analysis revealed that these differentially expressed proteins mainly included apoptosis-associated proteins, axon guidance-associated proteins, axonogenesis-associated proteins and mitochondrial respiratory chain complex. Among these differentially expressed mitochondrial proteins, GRP75 (75kDa glucose-regulated protein) and GRP78 (78kDa glucose-regulated protein) were found to be significantly down-regulated as confirmed by Western-blot analysis. The down-regulation of GRP75 was shown to promote apoptosis. The down-regulation of GRP78/BiP could up-regulate endoplasmic reticulum (ER) stress mediators and thus cause apoptosis. Our study suggested that these differentially expressed mitochondrial proteins such as GRP75 and GRP78 could be involved in neurotoxicity caused by long-term low-dose copper exposure and serve as potential molecular targets for the treatment of copper neurotoxicity.
authors: College of Pharmacy, Jinan University, Guangdong 510632, China; Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors: Xuemei
authors: X
authors: Lin
authors: Thyroid & Breast Surgery Department, Hubei Maternal & Children Hospital, Wuhan, Hubei, China.
authors: Gang
authors: G
authors: Wei
authors: The Emergency Department, Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China.
authors: Zhijun
authors: Z
authors: Huang
authors: Department of Neurology, Shanghai Jiaotong University Affiliated the Sixth Hospital, Shanghai 200233, China.
authors: Zhongsen
authors: Z
authors: Qu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors: Xinfeng
authors: X
authors: Huang
authors: College of Pharmacy, Jinan University, Guangdong 510632, China. Electronic address: huax_mail@126.com.
authors: Hua
authors: H
authors: Xu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors: Jianjun
authors: J
authors: Liu
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
authors: Zhixiong
authors: Z
authors: Zhuang
authors: Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China. Electronic address: xifeiyang@gmail.com.
authors: Xifei
authors: X
authors: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003300:Copper / Q000633:toxicity*; D060766:Drinking Water; D004579:Electron Transport / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D020258:Neurotoxicity Syndromes / Q000235:genetics* / Q000378:metabolism*; D040901:Proteomics
chemical_list: D051017:Apoptosis Regulatory Proteins; D060766:Drinking Water; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D003300:Copper; C029892:cupric chloride
keywords: Copper; Mitochondria; Neurotoxicity; Proteomics