Proteoglycan synthesis in normal and Lowe syndrome fibroblasts
Lowe (oculocerebrorenal) syndrome (LS) is an X-linked disorder characterized by congenital cataracts, generalized hypotonia, mental retardation, and renal Fanconi syndrome. The basic defect remains unknown, but the possibility that fibroblasts express reduced sulfation of glycosaminoglycans has been studied in several laboratories. A mechanism involving overproduction of an enzyme (nucleotide pyrophosphatase) active against adenosine 3'-phosphate, 5'-phosphosulfate (PAPS) has been postulated. Decreased synthesis of normally sulfated glycosaminoglycans was also reported. We measured the synthesis of proteoglycans and glycosaminoglycans by incorporation of (/sup 3/H)glucosamine and Na/sub 2/(/sup 35/)SO/sub 4/ into cultured fibroblasts from four LS patients and related it directly to the synthesis in six normal fibroblast cultures. We found that the rate of synthesis varied greatly among the normal cultures (cv, 30%), but not significantly between LS and the normal. The LS fibroblasts' ability to sulfate glycosaminoglycans was assayed as the amount of /sup 3/H-glycosaminoglycan eluting at low ionic strength on anion exchange chromatography, the amount of non-sulfated disaccharide present in chondroitinase digests of labeled proteoglycans, and the ratio of /sup 35/S to 3H incorporation into proteoglycans. Each parameter suggested that the LS cells were synthesizing normally sulfated glycosaminoglycans (e.g. % delta Di-0S, 21 +/- 6 in normal; 27 +/- 6 in LS). The cells' ability to sulfate glycosaminoglycans was tested under conditions of markedly stimulated glycosaminoglycan synthesis, by treating the cultures with a beta-D-xyloside.
- Research Organization:
- National Institute of Child Health and Human Development, Bethesda, MD
- OSTI ID:
- 6501198
- Journal Information:
- J. Biol. Chem.; (United States), Vol. 12
- Country of Publication:
- United States
- Language:
- English
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GLUCOPROTEINS
BIOSYNTHESIS
CONGENITAL DISEASES
FIBROBLASTS
HYALURONIC ACID
ION EXCHANGE CHROMATOGRAPHY
MENTAL DISORDERS
PATIENTS
SKIN
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
BODY
CARBOHYDRATES
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MUCOPOLYSACCHARIDES
ORGANIC COMPOUNDS
ORGANS
POLYSACCHARIDES
PROTEINS
SACCHARIDES
SEPARATION PROCESSES
SOMATIC CELLS
SYNTHESIS
550201* - Biochemistry- Tracer Techniques
550901 - Pathology- Tracer Techniques