Lower copper, zinc-superoxide dismutase protein but not mRNA in organs of copper-deficient rats.
Copper deficiency was induced in Sprague Dawley rats by dietary restriction to confirm and extend studies on copper, zinc-superoxide dismutase (Cu,Zn-SOD). Male rats restricted from copper in two models, a traditional postweanling model examining 50-day-old rats fed a low copper diet for 32 days (postnatal) and a gestational-lactational model examining 23-day-old male offspring of dams started on copper deficiency at day 7 of gestation (perinatal), showed signs of severe copper deficiency including anemia, and cardiac hypertrophy. Compared to control rats, copper-deficient rats exhibited lower copper concentrations in the liver, heart, brain, and kidney and lower Cu,Zn-SOD activity in the same organs with the exception of the brain in the postnatal model. In addition, there was a significant reduction in Cu,Zn-SOD protein detected by Western immunoblot proportional (r = 0.96) to the reduction in Cu,Zn-SOD activity. In the liver the reduction in Cu,Zn-SOD protein was approximately 50%. The reduction in Cu,Zn-SOD protein is likely due to a post-transcriptional mechanism as steady-state Cu,Zn-SOD mRNA levels measured by Northern hybridization were not altered by copper deficiency in any organ studied (liver, heart, and brain). Perhaps apo-Cu,Zn-SOD is degraded faster than fully metal-loaded enzyme. The loss of Cu,Zn-SOD activity and protein reduces the antioxidant defense capacity of copper-deficient organs.
Prohaska
J R
JR
Department of Biochemistry and Molecular Biology, University of Minnesota Duluth, Duluth, Minnesota 55812, USA. jprohask@d.umn.edu
Brokate
B
B
D000818:Animals; D001483:Base Sequence; D003300:Copper / Q000172:deficiency*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution
D017931:DNA Primers; D012333:RNA, Messenger; D003300:Copper; D013482:Superoxide Dismutase