Effect of 2-aminoethyl-L-cysteine on collagen accumulation in isolated hepatic granulomas.
Hydroxylysine residues are important structural components of collagen as sites of glycosylation and cross-linking. Because hydroxylysine is formed from lysine by post-translational enzymatic hydroxylation, we examined the effects of incorporation of a lysine analogue that could interfere with hydroxylation. For this purpose, we synthesized 35S-labeled 2-aminoethyl cysteine. By addition of this compound to a smooth muscle cell culture, we obtained radiolabeled collagen which, upon acid hydrolysis, yielded the intact labeled analogue, thus demonstrating incorporation of the compound into collagen. Using a model hepatic collagen synthesizing system, freshly isolated granulomas derived from mouse livers after 8 weeks of infection with Schistosoma mansoni, incubation over a period of 7 days with [14C]proline to measure collagen production, demonstrated a reduction in acid-precipitable [14C]hydroxyproline per milligram DNA in granuloma cultures incubated with 2-aminoethyl cysteine compared to control cultures, and the effect was dose-related. That this decrease was selective for collagen accumulation over noncollagenous proteins was demonstrated by the finding of a significant reduction in the [14C]hydroxyproline/[14C] proline ratios compared to controls. A maximum incorporation of 10 residues of analogue/1000 residues was achieved. While the extent of hydroxylation of proline in collagen remained unchanged, hydroxylation of lysine decreased with increasing amounts of analogue incorporated. We conclude that in our system, 2-aminoethyl cysteine is incorporable into collagen. In a dose-related fashion, it selectively diminishes collagen accumulation compared to control.
D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006099:Granuloma / Q000209:etiology / Q000378:metabolism; D006900:Hydroxylation; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D051379:Mice; D011392:Proline / Q000378:metabolism; D012552:Schistosomiasis
C000204:S-2-aminoethyl cysteine; D003094:Collagen; D011392:Proline; D008239:Lysine; D003545:Cysteine; D006909:Hydroxyproline