title: Featured Article: Effect of copper on nuclear translocation of copper chaperone for superoxide dismutase-1.
abstract: Copper chaperone for superoxide dismutase-1 (CCS-1), facilitating copper insertion into superoxide dismutase 1 (SOD-1), is present in the nucleus. However, it is unknown how CCS-1 is translocated to the nucleus. The present study was undertaken to determine the effect of copper on nuclear translocation of CCS-1. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia, causing an increase in both copper and CCS-1 in the nucleus. Treatment with tetraethylenepentamine (TEPA) not only decreased the total cellular concentration and the nuclear translocation of copper, but also completely suppressed the entry of CCS-1 to the nucleus. On the other hand, siRNA targeting CCS-1 neither inhibited the increase in total concentrations nor blocked the nuclear translocation of copper. This study thus demonstrates that under hypoxia condition, both copper and CCS-1 are transported to the nucleus. The nuclear translocation of CCS-1 is copper dependent, but the nuclear translocation of copper could take place alternatively in a CCS-1-independent pathway.
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA yjkang01@louisville.edu.
authors.forename: Y James
authors.initials: YJ
authors.lastname: Kang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects*; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D003300:Copper / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference
chemical_list: C114678:CCS protein, human; D005029:Ethylenediamines; D018832:Molecular Chaperones; D003300:Copper; C034269:tetraethylenepentamine
keywords: Copper; copper chaperone for superoxide dismutase-1; human umbilical vein endothelial cells; hypoxia-inducible factor-1; nucleus; translocation