title: Metallochaperone for Cu,Zn-superoxide dismutase (CCS) protein but not mRNA is higher in organs from copper-deficient mice and rats.
abstract: Cu,Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats and mice have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. SOD1 interacts with and requires its metallochaperone CCS for donating copper. We produced dietary Cu deficiency in rodents to determine if the reduction in SOD1 was related to the level of its specific metallochaperone CCS. CCS levels determined by immunoblot were 2- to 3-fold higher in liver, heart, kidney, and brain from male Cu-deficient rats and mice under a variety of conditions. CCS was also higher in livers of Cu-deficient dams. Interestingly, CCS levels in brain of Cu-deficient mice were also higher even though SOD1 activity and protein were not altered, suggesting that the rise in CCS is correlated with altered Cu status rather than a direct result of lower SOD1. A DNA probe specific for rat CCS detected a single transcript by Northern blot hybridization with liver RNA. CCS mRNA levels in mouse and rat liver were not altered by dietary treatment. These results suggest a posttranscriptional mechanism for higher CCS protein when Cu is limiting in the cell, perhaps due to slower protein turnover. Elevation in CCS level is one of the most dramatic alterations in Cu binding proteins accompanying Cu deficiency and may be useful to assess Cu status.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Minnesota Duluth School of Medicine, 1035 University Drive, Duluth, MN 55812, USA. jprohask@d.umn.edu
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Prohaska
authors.forename: Margaret
authors.initials: M
authors.lastname: Broderius
authors.forename: Bruce
authors.initials: B
authors.lastname: Brokate
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003300:Copper / Q000172:deficiency* / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*
chemical_list: C114678:CCS protein, human; C491962:Ccs protein, mouse; C491961:Ccs protein, rat; D018832:Molecular Chaperones; D012333:RNA, Messenger; D003300:Copper; D013482:Superoxide Dismutase