Diabetes induced glycation of collagen inhibits the binding step of collagen phagocytosis.
Published: 2006
Language: eng
Number of pages: 64
ISBN-13: 9780494210918
Description: As physiological collagen turnover is mediated by the intracellular phagocytic pathway, we studied the impact of diabetes-induced glycation of collagen on the binding step of phagocytosis. Collagen glycation was modeled with methylglyoxal, a glucose metabolite that modifies arginine and lysine residues. Glycation was authenticated by fluorescence photometry, solubility and cross-linking. The proportion of phagocytic cells was estimated by flow cytometry. Glycation inhibited collagen binding in a time and concentration-dependent manner. Inhibition of binding was reversed by aminoguanidine. Glycation inhibited collagen binding strength and intracellular calcium signaling. MGO glycation of triple helical collagen peptides mimicking the alpha2beta1 integrin binding site of collagen induced modification of arginine in the critical GFOGER integrin recognition sequence of collagen. MGO-induced cross-linking of lysines played only a small rote in binding inhibition. Conclusion: diabetes-induced loss of connective tissue homeostasis may involve glycation-mediated modifications of collagen that are required for recognition and binding in the intracellular, phagocytic pathway.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1439.

Thesis (M.Sc.)--University of Toronto, 2006.

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