Abnormal glycosylation of hemopexin in arthritic rats can be blocked by bindarit.

Abstract

Induction of arthritis in rats with Freund's complete adjuvant was accompanied by a distinctive alteration of concanavalin A (Con-A) reactivity in their serum proteins in which the concentrations of selected Con-A reactive proteins were significantly higher when compared to healthy rats. To assess if the observed increase in Con-A reactivity of specific serum proteins reflects an increase in carbohydrate moieties in these proteins in addition to an increase in their protein concentrations, a heme binding serum glycoprotein, hemopexin, also an acute phase reactant, was selected as a marker protein. Hemopexin was purified to apparent homogeneity from pools of serum samples derived from rats with yeast induced inflammation, a monospecific polyclonal antibody was prepared and was used for immunoblot analysis. It was noted that the concentration of hemopexin increased in rats with adjuvant induced arthritis; however, its concentration fell to normal levels after administration with a newly synthesized drug, bindarit, (2-[(1-benzyl-indazol-3-yl)methoxy]-2-methyl propionic acid, C19H20N2O3. Hemopexin was micropurified individually from healthy rats, adjuvant induced arthritic rats, and adjuvant arthritic rats treated with bindarit, cleaved with a Glu-C endopeptidase, Staphylococcus aureus protease V8, and the resultant peptide fragments resolved by SDS-PAGE and examined by silver staining, Coomassie blue staining, and lectin blots using Con-A. It was subsequently noted that hemopexin isolated from adjuvant induced arthritic rats showed a significant increase in Con-A reactivity in selected peptide fragments and that such an increase in glycosylation could be reversed to a pattern similar to healthy rats following treatment with bindarit.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: L Saso, B Silvestrini, I Zwain, A Guglielmotti, M R Luparini, V Cioli, C Y Cheng
• Journal: The Journal of rheumatology (J Rheumatol) Vol. 19 Issue 12 Pg. 1859-67 (Dec 1992) ISSN: 0315-162X [Print] Canada
• PMID: 1284132 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Proteins
• Indazoles
• Propionates
• Concanavalin A
• Freund's Adjuvant
• Hemopexin
• Endopeptidases
• bindarit

Topics

• Acute-Phase Reaction
• Amino Acid Sequence
• Animals
• Arthritis, Experimental (metabolism)
• Blood Proteins (metabolism)
• Chromatography, High Pressure Liquid
• Concanavalin A (pharmacology)
• Electrophoresis, Polyacrylamide Gel
• Endopeptidases (analysis)
• Freund's Adjuvant
• Glycosylation (drug effects)
• Hemopexin (isolation & purification, metabolism)
• Immunoblotting
• Indazoles (pharmacology)
• Molecular Sequence Data
• Propionates (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Staining and Labeling