Human plasma inactive renin: purification and activation by proteases.
A new affinity chromatographic procedure was devised to purify inactive renin by using a selective hydrophobic interaction of inactive renin to octyl-Sepharose. Additional extensive purification was accomplished by immunoaffinity chromatography on antihuman renin immunoglobulin G-Sepharose. A trace amount of active renin was removed by chromatography on pepstatin-Sepharose. Human plasma inactive renin purified by this method was free from protease inhibitors and permitted the investigation of protease-mediated activation without the acid treatment which was used previously to remove inhibitors. Human plasma kallikrein, human plasmin, cathepsin B1, and arginine esteropeptidases associated with mouse epidermis growth factor and nerve growth factor were effective activators. Human urinary kallikrein, hog pancreatic kallikrein, and rat urinary esterase A were inefficient activators of low potency. Thrombin, factor Xa, factor XIIa, and urokinase did not activate inactive renin. The in vitro activation of 56,000-dalton inactive renin by these proteases was not accompanied by a recognizable reduction in molecular weight. Activation required plasma albumin, presumably as a protecting substance. These results suggest that human inactive renin can be activated by a minimum change in its molecular size.
D002401:Cathepsin B; D002403:Cathepsins / Q000494:pharmacology; D002846:Chromatography, Affinity; D004789:Enzyme Activation / Q000187:drug effects; D005341:Fibrinolysin / Q000494:pharmacology; D006801:Humans; D007158:Immunologic Techniques; D007610:Kallikreins / Q000494:pharmacology; D001121:Lysine Carboxypeptidase / Q000494:pharmacology; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000494:pharmacology*; D012083:Renin / Q000097:blood* / Q000302:isolation & purification; D014357:Trypsin / Q000494:pharmacology
D002403:Cathepsins; D010447:Peptide Hydrolases; D001121:Lysine Carboxypeptidase; D007610:Kallikreins; D014357:Trypsin; D005341:Fibrinolysin; D002401:Cathepsin B; D012083:Renin