Binding of 92 kDa and 72 kDa progelatinases to insoluble elastin modulates their proteolytic activation.
92 kDa and 72 kDa gelatinases, two neutral proteinases exhibiting elastinolytic activity and secreted as zymogens by aortic smooth muscle cells, were shown to bind to insoluble elastin. The active form of each enzyme interacted with substrate more avidly than latent form. Once bound to insoluble elastin, 92 kDa progelatinase was totally unaffected by any potential activators tested (tissue kallikrein, neutrophil elastase, plasmin, and stromelysin-1), except aminophenylmercuric acetate (APMA). Binding of 72 kDa progelatinase to insoluble elastin induced a fast autoactivation of the proenzyme followed by its inactivation. This process can be partly inhibited by tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), EDTA and a synthetic inhibitor of matrix metalloproteinases (BB-94). Such an autoactivation process was also partially observed following adsorption of 72 kDa gelatinase to elastin-derived peptides but not to gelatin. Therefore, elastin can act as a template to direct its own proteolysis by 72 kDa gelatinase; such a mechanism could be relevant to the focal elastolysis in the arterial wall during arteriosclerosis.
Emonard
H
H
Laboratoire de Biochimie, CNRS UPRESA 6021, Faculté de Médecine de Reims, France.
Hornebeck
W
W
D000818:Animals; D002417:Cattle; D004549:Elastin / Q000737:chemistry / Q000378:metabolism*; D010450:Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D011506:Proteins / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2
D004792:Enzyme Precursors; D011480:Protease Inhibitors; D011506:Proteins; D013876:Thiophenes; D019716:Tissue Inhibitor of Metalloproteinase-2; D010649:Phenylalanine; D004549:Elastin; C080985:batimastat; D010450:Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase