Localization of urinary lactosylceramide in cytoplasmic vesicles of renal tubular cells in homozygous familial hypercholesterolemia

Subroto B Chatterjee, P. O. Kwiterovich, P. Gupta, Y. S. Erozan, C. R. Alving, R. L. Richards

Research output: Contribution to journalArticle

Abstract

An average 15-fold increase in lactosylceramide (LacCer) in the sediment of receptor-negative, familial hypercholesterolemic (FH) homozygotes has been reported. We report here the abnormal urinary excretion of significant numbers of renal tubular cells in eight FH homozygotes. The mean activity of γ-glutamyltransferase, a marker for renal tubular cells, was twice as high in urinary sediment of FH homozygotes as in normals. Membrane-enclosed cytoplasmic vesicles that stained strongly positive with a fluorescein-labeled antibody against LacCer were found in the renal tubular cells of all homozygotes except two who had undergone a portacaval shunt. These two had normal urinary levels of LacCer, and the cytoplasmic vesicles were vacuolated. In the other six, most of the fluorescent antibody label was intracellular and perinuclear. The cytoplasmic vesicles stained strongly with polychromatic Papanicolaou stain, periodic acid/Schiff reagent, and oil red O. Electron microscopy revealed perinuclear membrane-enclosed lipid and free lipid droplets. When two FH homozygotes, who excreted increased LacCer, underwent plasma exchange, the cytoplasmic vesicles became empty, and the urinary LacCer level decreased into the normal range. We conclude that the increased urinary excretion of LacCer in FH homozygotes occurs in renal tubular cells and that the intracellular location of LacCer is within cytoplasmic vesicles. The presence of LacCer within these vesicles can be modulated by treatment with plasma exchange.

Original languageEnglish (US)
Pages (from-to)1313-1317
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume80
Issue number5 I
StatePublished - 1983

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Cytoplasmic Vesicles
Hyperlipoproteinemia Type II
Homozygote
Kidney
Plasma Exchange
Surgical Portacaval Shunt
Periodic Acid
CDw17 antigen
Antibodies
Membrane Lipids
Fluorescein
Electron Microscopy
Reference Values
Coloring Agents
Membranes

ASJC Scopus subject areas

  • Genetics
  • General

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Localization of urinary lactosylceramide in cytoplasmic vesicles of renal tubular cells in homozygous familial hypercholesterolemia. / Chatterjee, Subroto B; Kwiterovich, P. O.; Gupta, P.; Erozan, Y. S.; Alving, C. R.; Richards, R. L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 80, No. 5 I, 1983, p. 1313-1317.

Research output: Contribution to journalArticle

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T1 - Localization of urinary lactosylceramide in cytoplasmic vesicles of renal tubular cells in homozygous familial hypercholesterolemia

AU - Chatterjee, Subroto B

AU - Kwiterovich, P. O.

AU - Gupta, P.

AU - Erozan, Y. S.

AU - Alving, C. R.

AU - Richards, R. L.

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N2 - An average 15-fold increase in lactosylceramide (LacCer) in the sediment of receptor-negative, familial hypercholesterolemic (FH) homozygotes has been reported. We report here the abnormal urinary excretion of significant numbers of renal tubular cells in eight FH homozygotes. The mean activity of γ-glutamyltransferase, a marker for renal tubular cells, was twice as high in urinary sediment of FH homozygotes as in normals. Membrane-enclosed cytoplasmic vesicles that stained strongly positive with a fluorescein-labeled antibody against LacCer were found in the renal tubular cells of all homozygotes except two who had undergone a portacaval shunt. These two had normal urinary levels of LacCer, and the cytoplasmic vesicles were vacuolated. In the other six, most of the fluorescent antibody label was intracellular and perinuclear. The cytoplasmic vesicles stained strongly with polychromatic Papanicolaou stain, periodic acid/Schiff reagent, and oil red O. Electron microscopy revealed perinuclear membrane-enclosed lipid and free lipid droplets. When two FH homozygotes, who excreted increased LacCer, underwent plasma exchange, the cytoplasmic vesicles became empty, and the urinary LacCer level decreased into the normal range. We conclude that the increased urinary excretion of LacCer in FH homozygotes occurs in renal tubular cells and that the intracellular location of LacCer is within cytoplasmic vesicles. The presence of LacCer within these vesicles can be modulated by treatment with plasma exchange.

AB - An average 15-fold increase in lactosylceramide (LacCer) in the sediment of receptor-negative, familial hypercholesterolemic (FH) homozygotes has been reported. We report here the abnormal urinary excretion of significant numbers of renal tubular cells in eight FH homozygotes. The mean activity of γ-glutamyltransferase, a marker for renal tubular cells, was twice as high in urinary sediment of FH homozygotes as in normals. Membrane-enclosed cytoplasmic vesicles that stained strongly positive with a fluorescein-labeled antibody against LacCer were found in the renal tubular cells of all homozygotes except two who had undergone a portacaval shunt. These two had normal urinary levels of LacCer, and the cytoplasmic vesicles were vacuolated. In the other six, most of the fluorescent antibody label was intracellular and perinuclear. The cytoplasmic vesicles stained strongly with polychromatic Papanicolaou stain, periodic acid/Schiff reagent, and oil red O. Electron microscopy revealed perinuclear membrane-enclosed lipid and free lipid droplets. When two FH homozygotes, who excreted increased LacCer, underwent plasma exchange, the cytoplasmic vesicles became empty, and the urinary LacCer level decreased into the normal range. We conclude that the increased urinary excretion of LacCer in FH homozygotes occurs in renal tubular cells and that the intracellular location of LacCer is within cytoplasmic vesicles. The presence of LacCer within these vesicles can be modulated by treatment with plasma exchange.

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