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.
Similar content being viewed by others
References
Glomset JA, Assmann G, Gjone E, Norum KR: Lecithin:cholesterol acyltransferase deficiency and fish eye disease. In: CR Scriver, AL Beaudet, WS Sly, D Valle (eds). The Metabolic Basis of Inherited Disease. McGraw-Hill, Inc., New York, 1995, pp 1933–1951
Torsvik H, Berg K, Magnani HN, McConathy WJ, Alaupovic P, Gjone E: Identification of the abnormal cholestatic lipoprotein (Lp-X) in familial lecithin:cholesterol acyltransferase deficiency. FEBS Lett 24:165–167, 1972
Seidel D, Gjone E, Blomhoff JP, Geisen HP: Plasma lipoproteins in patients with familial plasma lecithin:cholesterol acyltransferase (LCAT) deficiency–studies on the apolipoprotein composition of isolated fractions with identification of Lp-X. Horm Metab Res Suppl 4: 6–11, 1974
Ritland S, Gjone E: Quantitative studies of lipoprotein-X in familial lecithin:cholesterol acyltransferase deficiency and during cholesterol esterification. Clin Chem Acta 59: 109–119, 1975
Guerin M, Dolphin PJ, Chapman MJ: Familial lecithin:cholesterol acyltransferase deficiency: Further resolution of lipoprotein particle heterogeneity in the low density interval. Atherosclerosis 104: 195–212, 1993
Norum KR, Gjone E: Familial plasma lecithin:cholesterol acyltransferase deficiency. Biochemical study of a new inborn error of metabolism. Scand J Clin Lab Invest 20: 231–243, 1967
McLean JW: Molecular defects in the lecithin:cholesterol acyltransferase gene. In: NE Miller, AR Tall (eds). High Density Lipoproteins and Atherosclerosis III. Elsevier Science Publishers B.V. Amsterdam, 1992, pp 59–65
Klein H-G, Lohse P, Duverger N, Albers JJ, Rader DJ, Zech LA, Santamarina-Fojo S, Brewer Jr HB: Two different allelic mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in classic LCAT deficiency: LCAT(tyr83-stop) and LCAT(tyr156-asn). J Lipid Res 34: 49–58, 1993
Frohlich J, McLeod R, Pritchard PH, Fesmire J, McConathy W: Plasma lipoprotein abnormalities in heterozygotes for familial lecithin: cholesterol acyltransferase deficiency. Metabolism 37: 3–8, 1988
Hoving T, Gjone E: Familial plasma lecithin:cholesterol acyltransferase (LCAT) deficiency: Ultrastructural aspects of a new syndrome with particular reference to lesions in the kidneys and the spleen. Acta Pathol Microbiol Scand Section A 81: 681–697, 1973
Gjone E, Blomhoff J, Skarbovik AJ: Possible association between an abnormal low density lipoprotein and nephropathy in lecithin:cholesterol acyltransferase deficiency. Clin Chim Acta 54: 11–18, 1974
Stokke KT, Bjerve KS, Blomhoff JP, Oystese B, Flatmark A, Norum KR, Gjone E: Familial lecithin:cholesterol acyltransferase deficiency: Studies on lipid composition and morphology of tissues. J Clin Lab Invest 33: 93–100, 1974
Flatmark AL, Hovig T, Myhre E, Gjone E: Renal transplantation in patients with familial lecithin:cholesterol-acetyltransferase deficiency. Transplantation Proceedings IX: 1665–1671, 1977
Myhre E, Gjone E, Flatmark A, Hovig T: Renal Failure in familial lecithin-cholesterol acyltransferase deficiency. Nephron 18: 239–248, 1977
Magil A, Chase W, Frohlich J: Unusual renal biopsy findings in a patient with familial lecithin:cholesterol acyltransferase deficiency. Hum Pathol 13: 283–285, 1982
Ohta Y, Yamamoto S, Ysuchida H, Murano S, Saitoh Y, Yohjo S, Okada M: Nephropathy of familial lecithin-cholesterol acyltransferase deficiency: Report of a case. Am J Kidney Diseases VII: 41–46, 1986
Weber P, Owen JS, Desai K, Clemens MR: Hereditary lecithin: cholesterol acyltransferase deficiency: Case report of a German patient. Am J Clin Pathol 88: 510–516, 1987
Horina JH, Wirnsberger G, Horn S, Roob JM, Ratschek M, Holzer H, Pogglitsch H, Krejs GJ: Long-term follow-up of a patient with lecithin:cholesterol acyltransferase deficiency syndrome after kidney transplantation. Transplantation 56: 322–326, 1993
Sabesin SM: Cholestatic lipoproteins-their pathogenesis and significance. Gastroenterology 83: 704–709, 1982
Miller JP: Dyslipoproteinaemia of liver disease. Bailliere's Clin Endocrinology Met 4: 807–833, 1990
Narayanan S: Biochemistry and clinical relevance of Lipoprotein X. Ann Clin Lab Sci 14: 371–374, 1984
Patsch JR, Aune KC, Gotto Jr AM, Morrisett JD: Isolation, chemical characterization, and biophysical properties of three different abnormal lipoproteins: Lp-X1, Lp-X2, and Lp-X3. J Biol Chem 252: 2113–2120, 1977
OK, Frohlich J: Role of lecithin:cholesterol acyltransferase and apolipoprotein A-I in cholesterol esterification in Lipoprotein-X in vitro. J Lipid Res 36: 2344–2354, 1995
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275, 1951
Wengeler H, Seidel D: Does Lipoprotein-X (Lp-X) act as a substrate for the lecithin:cholesterol acyltransferase (LCAT)? Clin Chim Acta 45: 429–432, 1973
Patsch JR, Soutar AK, Morrissett JD, Gotto AM Jr, Smith LC: Lipoprotein-X: A substrate for lecithin:cholesterol acyltransferase. Eur J Clin Invest 7: 213–217, 1977
Patsch W, Patsch JR, Kunz F, Sailer S, Braunsteiner H: Studies on the degradation of Lipoprotein-X. Eur J Clin Invest 7: 523–530, 1977
Ritland S, Gjone E: Quantitative studies of Lipoprotein-X in familial lecithin:cholesterol acyltransferase deficiency and during cholesterol esterification. Clin Chim Acta 59: 109–119, 1975
Bowman RH, Maack T: Glucose transport by the isolated perfused rat kidney. Am J Physiol 222: 1499–1504, 1972
Anderson RL, Davis S: An organic phosphorus assay which avoid the use of hazardous perchloric acid. Clin Chim Acta 121: 111–116, 1982
Cao YZ, O K, Choy PC, Chan AC: Regulation by vitamin E of phosphatidylcholine metabolism in rat heart. Biochem J 247: 135–140, 1987
Michael P, Gillett T, Owen JS: Cholesterol esterifying enzymeslecithin: cholesterol acyltransferase (LCAT) and acylcoenzyme A:cholesterol acyltransferase (ACAT). In: CA Converse, ER Skinner (eds). Lipoprotein Analysis A Practical Approach. IRL Press, Oxford, 1992, pp 187–201
Kraemer FB, Patel S, Saedi MS, Sztalryd C: Detection of hormonesensitive lipase in various tissues. I. Expression of an HSL/bacterial fusion protein and generation of anti HSL antibodies. J Lipid Res 34: 663–671, 1993
Choy PC, Tardi PG, Mukherjee JJ: Lysophosphatidylcholine acyltransferase. Meth Enzymol 209: 80–86, 1992
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Karmin, O., Ly, M., Fang, D.Z. et al. Effect of Lipoprotein-X on lipid metabolism in rat kidney. Mol Cell Biochem 173, 17–24 (1997). https://doi.org/10.1023/A:1006836704042
Issue Date:
DOI: https://doi.org/10.1023/A:1006836704042