Cited by 21Proteoglycans and glycosaminoglycans researchOsteoarthritis Treatment and MechanismsProtease and Inhibitor Mechanisms

Mechanism for the decreased biosynthesis of cartilage proteoglycan in the scorbutic guinea pig

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Bird, T A, Schwartz, N B, Peterkofsky, B·1986·Journal of Biological Chemistry

Abstract

Our previous work showed that vitamin C deficiency caused about a 70-80% decrease in the incorporation of [35S]sulfate into proteoglycan of guinea pig costal cartilage, coordinately with a decrease in collagen synthesis (Bird, T. A., Spanheimer, R. G., and Peterkofsky, B. (1986) Arch. Biochem. Biophys. 246, 42-51). We examined the mechanism for decreased proteoglycan synthesis by labeling normal and scorbutic cartilage in vitro with radioactive precursors. Proteoglycan monomers from scorbutic tissue were of a slightly smaller average hydrodynamic size than normal but there was no difference in the size of the glycosaminoglycan chains isolated after papain digestion. The type of glycosaminoglycans synthesized and the degree of sulfation were unaffected as determined by chondroitinase ABC digestion and duel labeling with [35S]sulfate and [3H]glucosamine. Conversion of [3H]glucosamine to [3H]galactosamine also was unimpaired. There was about a 40% decrease in core protein synthesis, measured by [14C]serine incorporation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Nevertheless, decreased incorporation of [35S]sulfate into scorbutic tissue persisted in the presence of p-nitrophenyl-beta-D-xyloside and cycloheximide, which indicated that the site of the scorbutic defect was beyond core protein synthesis and xylosylation. Galactosyltransferase activity in scorbutic cartilage decreased to about one-third the levels in control samples in parallel with the decreases in proteoglycan and collagen synthesis. Our results suggest that the step catalyzed by this enzyme activity, the addition of galactose to xylose prior to chondroitin sulfate chain elongation, is the major site of the scorbutic defect in proteoglycan synthesis. Decreased enzyme activity may be related to increased cortisol levels in scorbutic serum.

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Crossref · 10.1016/s0021-9258(18)67363-6

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Authors
Bird, T. A., Schwartz, N. B., & Peterkofsky, B.
Affiliations
National Institutes of Health (US)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1986-08
Volume
261
Issue
24
Pages
11166-11172
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1597181974
Cited by
21
References
34
Citations by year
2021: 1
FWCI
1.11
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
Keywords
scurvy, galactosyltransferase, glycosaminoglycan sulfation, chondroitin sulfate, collagen synthesis, sulfate incorporation, cortisol
MeSH terms
Animals, Ascorbic Acid Deficiency, Cartilage, Chondroitin Lyases, Chromatography, Gel, Cycloheximide, Electrophoresis, Polyacrylamide Gel, Galactosamine, Glucosamine, Glycosides, Guinea Pigs, Hydrocortisone, Proteoglycans, Sulfates

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