Effect of Lipoprotein-X on lipid metabolism in rat kidney |
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Authors: | O Karmin May Ly Ding Z Fang Jiri Frohlich Patrick C Choy |
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Institution: | (1) Department of Pathology and Laboratory Medicine, University of British Columbia, Atherosclerosis Specialty Laboratory, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, Canada;(2) Department of Biochemistry and Molecular Biology, University of Manitoba, Winnipeg, Manitoba, Canada |
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Abstract: | Lipoprotein-X (Lp-X) is found in the plasma of patients with familiallecithin: cholesterol acyltransferase (LCAT) deficiency syndromes. Themajority of the patients with this disorder develop progressiveglomerulosclerosis. In this study, the effect of Lp-X on lipid metabolism inperfused rat kidney was investigated. Lp-X was isolated from plasma ofpatients with familial LCAT deficiency by sequential ultracentrifugation andgel filtration column chromatography. Rat kidneys were perfused for 1-2 hwith Krebs-Henseleit buffer containing 20 µM 1-14C]acetate or 20µM Me-3H]choline. In the presence of Lp-X, no significant differencein the incorporation of radioactivity into triglycerides, cholesterol,phosphocholine, CDP-choline and sphingomyelin was observed. However,incorporation of radioactivity into cholesteryl esters andphosphatidylcholine was significantly elevated in Lp-X perfused kidneys. Thecontents of cholesterol, cholesteryl esters and phosphatidylcholine werealso significantly increased in Lp-X perfused kidneys. The increase in lipidcontent in the Lp-X perfused kidney is attributed to the direct depositionof Lp-X lipids into the organ. The increase in the labelling of cholesterylesters was attributed to the increase of available substrate (cholesterol)for the acyl-CoA:cholesterol acyltransferase (ACAT) reaction. The increasein phosphatidylcholine labelling was caused by a reduced turnover of thenewly synthesized labelled phosphatidylcholine during Lp-X perfusion. |
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Keywords: | Lipoprotein-X LCAT deficiency kidneyperfusion cholesterol choelsteryl esters phosphatidycholine |
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