Effect of lipoprotein-X on lipid metabolism in rat kidney.
Lipoprotein-X (Lp-X) is found in the plasma of patients with familial lecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. The majority of the patients with this disorder develop progressive glomerulosclerosis. In this study, the effect of Lp-X on lipid metabolism in perfused rat kidney was investigated. Lp-X was isolated from plasma of patients with familial LCAT deficiency by sequential ultracentrifugation and gel filtration column chromatography. Rat kidneys were perfused for 1-2 h with Krebs-Henseleit buffer containing 20 microM [1-(14)C]acetate or 20 microM [Me-3H]choline. In the presence of Lp-X, no significant difference in the incorporation of radioactivity into triglycerides, cholesterol, phosphocholine, CDP-choline and sphingomyelin was observed. However, incorporation of radioactivity into cholesteryl esters and phosphatidylcholine was significantly elevated in Lp-X perfused kidneys. The contents of cholesterol, cholesteryl esters and phosphatidylcholine were also significantly increased in Lp-X perfused kidneys. The increase in lipid content in the Lp-X perfused kidney is attributed to the direct deposition of Lp-X lipids into the organ. The increase in the labelling of cholesteryl esters was attributed to the increase of available substrate (cholesterol) for the acyl-CoA:cholesterol acyltransferase (ACAT) reaction. The increase in phosphatidylcholine labelling was caused by a reduced turnover of the newly synthesized labelled phosphatidylcholine during Lp-X perfusion.
O
K
K
Department of Pathology and Laboratory Medicine, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
Ly
M
M
Fang
D Z
DZ
Frohlich
J
J
Choy
P C
PC
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000187:drug effects / Q000378:metabolism; D000085:Acetates / Q000378:metabolism; D000818:Animals; D002794:Choline / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D007863:Lecithin Cholesterol Acyltransferase Deficiency / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D008073:Lipoprotein-X / Q000008:administration & dosage / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D010477:Perfusion; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000085:Acetates; D008055:Lipids; D008073:Lipoprotein-X; D008074:Lipoproteins; D008243:1-Acylglycerophosphocholine O-Acyltransferase; D010741:Phospholipases A; D002794:Choline