Effect of cupric ions on serum and liver cholesterol metabolism.
Cupric ions were administered subcutaneously to male Sprague-Dawley r rats at a single dose of 200 mumol/kg. At 24 hr after administration, a remarkable increase of total and free cholesterol was seen in the rat serum. Also, when lecithin-cholesterol acyltransferase (LCAT) (E.C. 2.3.1.43) activity was expressed as the percentage of the total serum that free cholesterol esterified, the acyltransferase activity in rats treated with cupric ions showed a slight decrease while the triglyceride content in rat serum and liver decreased by 54% and 61%, respectively. However, the content of hepatic cholesterol in rats treated with cupric ions did not show such a marked change. On the other hand, acid cholesteryl ester hydrolase activity (Acid CEH) (E.C. 3.1.1.14) in liver lysosomes of rats treated with cupric ions showed a marked decrease with increasing cupric ion concentration both in vivo and in vitro. Furthermore, cupric ions caused a marked release of the lysosomal enzymes cathepsin D and beta-glucuronidase into the cytosolic fraction. The changes in acid cholesteryl ester hydrolase activity induced by cupric ions appear to be a direct effect of cupric ions on the enzyme. These results suggest that excessive cupric ion concentrations could cause various disorders in lipid metabolism.
Tanaka
M
M
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Iio
T
T
Tabata
T
T
D000818:Animals; D002402:Cathepsin D / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D014280:Triglycerides; D003300:Copper; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D002787:Sterol Esterase; D005966:Glucuronidase; D002402:Cathepsin D; C029892:cupric chloride