Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation.
1. Cathepsin B, a tissue (lysosomal) proteinase, and two humoral proteinases, plasmin and kallikrein, activate the latent collagenase ('procollagenase') which is released by mouse bone explants in culture. Other lysosomal proteinases (carboxypeptidase B, cathepsin C and D) and thrombin did not activate the procollagenase. Dialysis of the culture fluids against 3M-NaSCN at 4 degrees C and, for some culture fluids, prolonged preincubation at 25 degrees C also caused the activation of procollagenase. 2. In all these cases, activation of procollagenase involved at least two successive steps: the activation of an endogenous latent activator present in the culture fluids and the activation of procollagenase itself. 3. An assay method was developed for the endogenous activator. Human serum, bovine serum albumin, casein and cysteine inhibited the endogenous activator at concentrations that did not influence the collagenase activity. N-Ethylmaleimide and 4-hydroxy-mercuribenzoate stimulated the endogenous activator, but iodoacetate had no effect. 4. It is proposed that cathepsin B, kallikrein and plasmin may play a role in the physiological activation of latent collagenase and thus initiate degradation of collagen in vivo. This may occur whatever the molecular nature of procollagenase (zymogen or enzyme-inhibitor complex) might be.
D000818:Animals; D001842:Bone and Bones / Q000201:enzymology; D002403:Cathepsins / Q000494:pharmacology; D017364:Collagenases; D003470:Culture Media; D046508:Culture Techniques; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology; D007610:Kallikreins / Q000494:pharmacology; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D003012:Microbial Collagenase / Q000378:metabolism*; D013861:Thiocyanates / Q000494:pharmacology
D003470:Culture Media; D004792:Enzyme Precursors; D013861:Thiocyanates; D002403:Cathepsins; D007610:Kallikreins; D005341:Fibrinolysin; D017364:Collagenases; C022440:procollagenase; D003012:Microbial Collagenase