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 postwe anling model examining 50-day-old rats fed a low copper diet for 32 days (p ostnatal) and a gestational-lactational model examining 23-day-old male off : spring of dams started on copper deficiency at day 7 of gestation (perina tal), showed signs of severe copper deficiency including anemia, and cardia c hypertrophy. Compared to control rats, copper-deficient rats exhibited lo wer 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 th e postnatal model. In addition, there was a significant reduction in Cu,Zn- SOD protein detected by Western immunoblot proportional (r = 0.96) to the r eduction in Cu,ZnSOD activity. In the liver the reduction in Cu,Zn-SOD prot ein was approximately 50%. The reduction in Cu,ZnSOD protein is likely due to a post-transcriptional mechanism as steady-state Cu,Zn-SOD mRNA levels m easured by Northern hybridization were not altered by copper deficiency in any organ studied (liver, heart, and brain). Perhaps apo-Cu,Zn-SOD is degra ded faster than fully metal-loaded enzyme. The loss of Cu,Zn-SOD activity a nd protein reduces the antioxidant defense capacity of copper-deficient org ans. (C) 2001 Academic Press.