Regulation of sphingolipid synthesis in renal cells from normal subjects and familial hypercholesterolemic subjects
The authors have investigated the effects of lipoproteins on sphingolipid metabolism in proximal renal tubular cells from normal subjects and low density lipoprotein (LDL) receptor-negative homozygous familial hypercholesterolemic (FH) subjects (TB,BA,DD,VH) employing (/sup 3/H)serine and (/sup 3/H)glucose. The results were: normal cells - 1) LDL (25 ..mu..g/ml) decreased the incorporation of (/sup 3/H)glucose and (/sup 3/H)serine into ceramide and LacCer about 2-3 fold; 2) the incorporation of (/sup 3/H)serine into sphingomyelin was also reduced 2 fold by LDL; 3) LDL modified by reductive methylation of lysine residues (which is not recognized by the LDL receptor) did not decrease the incorporation of (/sup 3/H)glucose and (/sup 3/H)serine into sphingolipids; FH cells - In contrast to normal cells, LDL (100 ..mu..g/ml) stimulated both the incorporation of (/sup 3/H)glucose into LacCer and of (/sup 3/H)serine into ceramide, LacCer and sphingomyelin 2-3 fold in cells lacking LDL receptors. The authors conclude that the endogenous synthesis of sphingolipids in normal renal cells may be regulated by the LDL receptor. Lack of LDL receptor, as in FH cells, results in increased sphingolipid synthesis and storage of LacCer.
- Research Organization:
- Johns Hopkins Univ., Baltimore, MD
- OSTI ID:
- 7171353
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
AMINO ACIDS
BIOSYNTHESIS
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHOLESTEROL
ESTERS
GLUCOSE
HEXOSES
HYDROXY ACIDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
KIDNEYS
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MEMBRANE PROTEINS
METABOLISM
METHYLATION
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PHOSPHOLIPIDS
PROTEINS
RECEPTORS
SACCHARIDES
SERINE
SPHINGOMYELINS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS