Copper, zinc-superoxide dismutase protein but not mRNA is lower in copper-deficient mice and mice lacking the copper chaperone for superoxide dismutase.
Cu, Zn-superoxide dismutase (SOD1) is an abundant metalloenzyme important in scavenging superoxide ions. Cu-deficient rats have lower SOD1 activity and protein, possibly because apo-SOD1 is degraded faster than holo-SOD1. Previous work with mice lacking the Cu chaperone for SOD1 (CCS) indicated a drastic loss of SOD1 activity but not protein, suggesting an accumulation of apo-SOD1. We produced dietary Cu deficiency in mice to clarify this issue. Compared with Cu-deficient rats, reduction in liver SOD1 activity and protein was much less than Cu-deficient mouse dams and offspring. However, after perinatal Cu deficiency, 4-week-old mouse pups had lower levels of SOD1 activity and protein in liver and heart, but not brain, compared with Cu-adequate controls. Reduction in brain Cu was greater than liver. In CCS -/- mice, there was severe reduction in liver, heart, and brain SOD1 activity and protein. In fact, the reduction in activity was similar to the loss of protein. Neither Cu-deficient mouse liver nor CCS -/- mouse liver had altered SOD1 mRNA levels compared with control values. These results in mice are comparable with rats and suggest a posttranscriptional mechanism for reduction of SOD1 protein when Cu is limiting in SOD1.
Prohaska
Joseph R
JR
Department of Biochemistry and Molecular Biology, University of Minnesota Duluth School of Medicine, Duluth, Minnesota 55812, USA. jprohask@d.umn.edu
Geissler
Jacqueline
J
Brokate
Bruce
B
Broderius
Margaret
M
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D003300:Copper / Q000032:analysis / Q000172:deficiency*; D004032:Diet; D005260:Female; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D011247:Pregnancy; D011506:Proteins / Q000032:analysis; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000378:metabolism / Q000502:physiology*; D000072105:Superoxide Dismutase-1
C491962:Ccs protein, mouse; C491961:Ccs protein, rat; D018832:Molecular Chaperones; D011506:Proteins; D012333:RNA, Messenger; D003300:Copper; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1