Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas.
Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, F. Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase. Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was greater than 65% all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space.
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002645:Chickens; D004549:Elastin / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D007700:Kinetics; D008854:Microscopy, Electron; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*
D006025:Glycosaminoglycans; D004549:Elastin; D000594:Amino Acid Oxidoreductases; D008249:Protein-Lysine 6-Oxidase