Effect of colchicine on atherosclerosis. II. Biochemical studies on skin biopsies from patients treated perorally with colchicine.
The biosynthesis of proteins and glycosaminoglycans (GAGs) was determined in skin biopsies from atherosclerotic patients treated perorally for 3 months with 1 mg/day colchicine. The biopsies were incubated with 3H-glucosamine and 14C-proline for 5 h and subsequently digested with pronase. In an aliquot of the pronase digest, the specific radioactivity of 14C-proline and 14C-hydroxyproline were determined. The 3H-glucosamine-labeled GAGs were identified by specific enzymic assay and quantified after electrophoretic separation. 3 months treatment with colchicine did not modify the total amounts of proline and hydroxyproline in skin proteins, but diminished the amount of the GAGs as expressed by uronic acid content. Colchicine treatment decreased also the specific radioactivity of proline and hydroxyproline, which reflects a decrease of total protein and collagen synthesis. The incorporation of 3H-glucosamine in the 3H-GAGs was also decreased, mainly in hyaluronic acid. These results suggest that peroral administration of colchicine modifies the synthesis of extracellular matrix proteins and polysaccharides by skin fibroblasts.
D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism*; D001706:Biopsy; D002986:Clinical Trials as Topic; D003078:Colchicine / Q000627:therapeutic use*; D005260:Female; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D006909:Hydroxyproline / Q000032:analysis; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011392:Proline / Q000032:analysis; D014176:Protein Biosynthesis; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014574:Uronic Acids / Q000032:analysis
D006025:Glycosaminoglycans; D014574:Uronic Acids; D011392:Proline; D006909:Hydroxyproline; D003078:Colchicine