chondroitin-sulfates and Progeria

We report an unusual case with mental retardation, short stature, sparse scalp hair, prominence of scalp veins, atrophy of subcutaneous fat, pterygia of the neck and loose skin. The patient excreted greater amounts of low-sulphated chondroitin sulphate (LSC) in the urine than age-matched controls. The pattern of glycosaminoglycan in serum and its synthesis by the patient fibroblasts were normal. Collagen, elastin and decorin mRNA levels in the patient fibroblasts were also unaltered. These results suggest that this patient seems to be different from Lowe's syndrome and decorin-deficient progeroid. An abnormal LSC metabolism may be partially responsible for the pathology of these syndromes.

Topics: Abnormalities, Multiple; Cells, Cultured; Child; Chondroitin Sulfates; Fibroblasts; Glycosaminoglycans; Humans; Male; Progeria

WI-38 fibroblasts from 'normal' individuals and skin fibroblasts from patients displaying classical symptoms of progeria (accelerated aging) were maintained in tissue culture with and without periodic supplementation of 0.25 mg/ml of chondroitin-4-sulphate (C-4-S) during the ultimate phase of slowed division (phase 3). When C-4-S was not present in the culture medium, cell counts (not necessarily indicative of relative rates of cell division) and mean cell volumes were lower, and intracellular aberrations were higher, in both types of fibroblasts (normal and progeria) at, and even before, the 47th-50th and 13th-16th passages, respectively. The authors emphasise effects of C-4-S in preserving normal ultrastructure, pointing out that C-4-S does not fulfil the criteria of a mitogen and that any possible increases in rates of mitosis following supplementation with this substance are probably secondary to an enhanced metabolic environment.

Topics: Cell Survival; Cells, Cultured; Chondroitin; Chondroitin Sulfates; Fibroblasts; Humans; Progeria

The use of high-performance liquid chromatography for the quantification of glycosaminoglycan disaccharides has been hampered by the inability to isocratically resolve the chondroitinase digestion products 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-glucose (delta Di-HA) and 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (delta Di-OS). To overcome this limitation, we have developed a solvent system capable of resolving delta Di-HA, delta Di-OS, 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (delta Di-6S), and 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (delta Di-4S). Integrator responses were linear from 1 microgram down to 25 ng for delta Di-HA, delta Di-OS, and delta Di-4S and down to 100 ng for delta Di-6S. This method was used to examine changes in the content of urinary hyaluronic acid and chondroitin sulfates isolated from normal individuals and from patients with Lowe Syndrome, Werner Syndrome, and Hutchinson-Gilford Progeria Syndrome. We confirmed that the HPLC method gave results comparable to colorimetric methods.

Topics: Chondroitin; Chondroitin Lyases; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Glycosaminoglycans; Humans; Hyaluronic Acid; Oculocerebrorenal Syndrome; Progeria; Werner Syndrome