Turnover of sulfated glycosaminoglycans in fibroblasts derived from patients with Werner's syndrome

Journal Article · Sun Feb 01 04:00:00 EST 1987 · Exp. Cell Res.; (United States)

DOI:https://doi.org/10.1016/0014-4827(87)90007-3· OSTI ID:6943079

Cowles, E A; Brauker, J H; Anderson, R L

Fibroblasts derived from patients with Werner's syndrome (WS) were incubated with radioactive sulfate to study the incorporation of 35S into glycosaminoglycans (GAGs). The accumulation of cell-associated 35S radioactivity in the GAGs of WS fibroblasts was consistently higher than parallel accumulation in normal human fibroblasts, but was substantially less than in fibroblasts derived from patients with Hurler's syndrome (HS). However, when fibroblasts were labeled with 35SO4(2-), trypsinized to remove extracellular and pericellular radioactive GAGs, replated, and chased to follow the fate of the intracellular radioactivity, both WS and normal cells showed a rapid release of the intracellular 35S, while HS cells showed little or no loss of intracellular radioactivity. The radioactivity released from WS and normal cells was of low molecular weight (LMW), eluting from gel filtration columns at the same position as free sulfate. These results establish that WS cells degrade intracellular sulfated GAGs and argue against the hypothesis that a defect in GAG degradation pathways is the basis for the increased level of cell-associated GAGs. Other possible explanations for the increased cell-associated (35S)GAGs in WS cells as compared with normal cells were also considered: increased GAG sulfation; an increase in GAG chain length; an increased rate of GAG synthesis; and a decreased rate of shedding of cell surface proteoglycan into the medium. No difference between normal and WS fibroblasts in any of the above parameters was observed. These results strongly imply that the primary biochemical defect in WS fibroblasts does not involve sulfated GAG metabolism.

• Research Organization: Michigan State Univ., East Lansing
• OSTI ID: 6943079
• Journal Information: Exp. Cell Res.; (United States), Journal Name: Exp. Cell Res.; (United States) Vol. 2; ISSN ECREA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
FIBROBLASTS
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
METABOLISM
MUCOPOLYSACCHARIDES
NUCLEI
ORGANIC COMPOUNDS
ORGANS
OXYGEN COMPOUNDS
POLYSACCHARIDES
RADIOISOTOPES
SACCHARIDES
SKIN
SOMATIC CELLS
SULFATES
SULFUR 35
SULFUR COMPOUNDS
SULFUR ISOTOPES
TRACER TECHNIQUES