Inhibition of copper-associated erythrocyte ghost membrane lipid peroxidation by hepatic cytosolic low molecular weight proteins.
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.
Homer
B L
BL
Department of Veterinary Pathology, College of Veterinary Medicine, Texas A&M University, College Station 77343-4463.
Pierce
K R
KR
Bridges
C H
CH
Womack
J E
JE
Sowa
B A
BA
Littell
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002845:Chromatography; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344
D002352:Carrier Proteins; C023548:copper-binding protein; D003300:Copper; C029892:cupric chloride