Factors Affecting the Proteolytic Degradation of Elastin

Abstract

Studies in our laboratory have been concerned with aspects of the interaction of elastin with pancreatic elastase in efforts to assess intrinsic and extrinsic factors which might be involved in the regulation of elastolysis in vivo. Previous studies by others have clearly shown that elastase-elastin interactions are principally governed by ionic forces distributed between the cationic enzyme and the presumably anionic substrate. Our studies have now shown that most of the dicarboxylic amino acids in elastin are amidated, rendering elastin a cationic protein containing very few negatively charged side chains. Further, we have demonstrated that elastin can be rendered highly anionic by complex formation with amphiphilic agents such as fatty acids, bile salts, and detergents. These complexes are much more susceptible to elastolysis than elastin, itself. Evidence has also been obtained that these agents induce conformational changes in insoluble elastin, reflected in losses in elasticity of elastic fibers. Additional studies have shown that the formation of sedimentable elastin-elastase complexes seem not only to be unrelated, but, possibly, counterproductive to peptide bond scission in elastin. Further, both elastolysis and enzyme binding relationships are markedly influenced by calcium ions and by amphiphilic elastin ligands.