Male weanling Fischer rats were injected ip once daily with either 12.5 mg/kg
body weight cupric chloride or 2 ml/kg
body weight saline for up to 70 days. As the hepatic cytosolic
copper increased in
copper-treated rats,
copper bound to
proteins of different molecular weights; this was determined by gel filtration chromatography. Hepatic cytosolic
copper from rats treated with
cupric chloride for 14 days eluted in 3 peaks. These included a 150,000 + dalton peak, a 29,000 dalton peak and an 11,000-12,800 dalton peak. In addition to these peaks, hepatic cytosolic
copper from rats treated with
cupric chloride for greater than or equal to 28 days also eluted in a 4th, but shorter, 6,000-7,000 dalton peak. Hepatic cytosolic
copper from saline-treated rats eluted only in a single 29,000 dalton peak. Experiments using an erythrocyte ghost membrane model of
copper-associated lipid peroxidation demonstrated that incubation of membranes with
protein-bound
copper eluted in the 11,000-12,000 dalton peak was associated with less lipid peroxidation than incubation of membranes with
cupric chloride or
protein-bound
copper eluted in the 150,000+ dalton peak. Experimental results suggest that the ability of
copper to catalyze lipid peroxidation is significantly reduced by binding with hepatic cytosolic low molecular weight
proteins but not by binding with hepatic cytosolic high molecular weight
proteins.