| The effects of 6-diazo-5-oxo-L-norleucine, a glutamine analogue, on the structure of the major cartilage proteoglycan synthesized by cultured chondrocytes. | |
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MedLine Citation:
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PMID: 3112139 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Incubation of embryonic chick chondrocytes with 6-diazo-5-oxo-L-norleucine (DON), a glutamine analogue, led to a dose-dependent inhibition of [35S]sulfate incorporation into proteoglycan. In the absence of exogenous L-glutamine, a maximal inhibition of 50-60% was achieved with DON concentrations greater than or equal to 1 microgram/ml (6 microM); the ED50 was approximately 0.2 microM. This inhibitory effect could be partially restored by the addition of 100-fold molar excess of either exogenous L-glutamine or M-glucosamine. The quantitative changes were due neither to inhibition of protein core synthesis nor to undersulfation of glycosaminoglycan chains. Rather, the proteoglycan synthesized in the presence of DON contained substantially fewer (approximately 50% of control) and smaller (10-15% of control, on the average) chondroitin sulfate chains as well as a paucity of keratan sulfate chains. The result of these structural changes was a proteoglycan with significantly lower molecular weight, buoyant density, and anionic charge. In spite of these modifications, the altered proteoglycan synthesized in the presence of DON was secreted normally and retained the ability to interact with exogenous hyaluronic acid and link proteins. The results of our experiments also indicate that DON substantially diminished the pool of hexosamine precursors required for glycosaminoglycan synthesis. We conclude that this decrease was responsible for the molecular alterations described above; and these, in turn, can account for the morphological changes previously seen in cartilage matrix synthesized in the presence of DON. |
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Authors:
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C C Clark; C F Richards; M Pacifici; R V Iozzo |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 262 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1987 Jul |
Date Detail:
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Created Date: 1987-09-04 Completed Date: 1987-09-04 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 10229-38 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azo Compounds / pharmacology* Cartilage / metabolism* Chick Embryo Chondroitin Lyases / metabolism Chromatography, Gel Diazooxonorleucine / pharmacology* Glycoside Hydrolases* Molecular Weight Protein Conformation / drug effects Proteoglycans / analysis, metabolism* beta-Galactosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AM-13812/AM/NIADDK NIH HHS; AM-20553/AM/NIADDK NIH HHS; AM-32481/AM/NIADDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Azo Compounds; 0/Proteoglycans; 764-17-0/Diazooxonorleucine; EC 3.2.1.-/Glycoside Hydrolases; EC 3.2.1.103/keratan-sulfate endo-1,4-beta-galactosidase; EC 3.2.1.23/beta-Galactosidase; EC 4.2.2.-/Chondroitin Lyases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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