title: Involvement of CTR1 and ATP7A in lead (Pb)-induced copper (Cu) accumulation in choroidal epithelial cells.
abstract: The blood-cerebrospinal fluid barrier (BCB) plays a key role in maintaining copper (Cu) homeostasis in the brain. Cumulative evidences indicate that lead (Pb) exposure alters cerebral Cu homeostasis, which may underlie the development of neurodegenerative diseases. This study investigated the roles of Cu transporter 1 (CTR1) and ATP7A, two Cu transporters, in Pb-induced Cu accumulation in the choroidal epithelial cells. Pb exposure resulted in increased intracellular (64)Cu retention, accompanying with up-regulated CTR1 level. Knockdown of CTR1 using siRNA before Pb exposure diminished the Pb-induced increase of (64)Cu uptake. The expression level of ATP7A was down-regulated following the Pb exposure. ATP7A siRNA knockdown, or PCMB treatment, inhibited the (64)Cu efflux from the cells, while the following additional incubation with Pb failed to further increase the intracellular (64)Cu retention. Cu exposure, or intracellular Cu accumulation following the tetracycline (Tet)-induced overexpression of CTR1, did not result in significant change in ATP7A expression. Taken together, these data indicate that CTR1 and ATP7A play important roles in Cu transport in choroidal epithelial cells, and the Pb-induced intracellular Cu accumulation appears to be mediated, at least in part, via the alteration of CTR1 and ATP7A expression levels following Pb exposure.
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Gang
authors: G
authors: Zheng
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Jieqiong
authors: J
authors: Zhang
authors: Department of Laboratory, Xijing Hospital, Fourth Military Medical University, Xi'an China.
authors: Yan
authors: Y
authors: Xu
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Xuefeng
authors: X
authors: Shen
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Han
authors: H
authors: Song
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Jinfei
authors: J
authors: Jing
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
authors: Wenjing
authors: W
authors: Luo
authors: School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: wzheng@purdue.edu.
authors: Wei
authors: W
authors: Zheng
authors: Department of Occupational and Environmental Health and The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an 710032, China. Electronic address: jy_chen@fmmu.edu.cn.
authors: Jingyuan
authors: J
authors: Chen
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D009942:Organometallic Compounds / Q000633:toxicity*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D009942:Organometallic Compounds; D012333:RNA, Messenger; C510533:Slc31a1 protein, rat; D003300:Copper; D000251:Adenosine Triphosphatases; C486202:Atp7a protein, rat; D000073840:Copper-Transporting ATPases; C008261:lead acetate; C029892:cupric chloride
keywords: ATP7A; ATP7B; ATPase, Cu(2+) transporting, alpha polypeptide; ATPase, Cu(2+) transporting, beta polypeptide; BCB; Blood–cerebrospinal fluid barrier; CNS; CSF; CTR1; Copper; Copper transporter 1; Cu transporter 1; DMT1; Lead; blood–cerebrospinal fluid barrier; central nervous system; cerebrospinal fluid; divalent metal transporter 1