Human placental ribonuclease inhibitor abolishes both angiogenic and ribonucleolytic activities of angiogenin.
Human placental ribonuclease inhibitor (PRI) abolishes both the ribonucleolytic activity of angiogenin toward 28S and 18S rRNA and its angiogenic activity on the chicken embryo chorioallantoic membrane. Treatment of the angiogenin-PRI complex with p-hydroxymercuribenzoate releases enzymatically active angiogenin. Assays measuring competition between angiogenin and bovine pancreatic ribonuclease A for PRI reveal that binding of the inhibitor to angiogenin is extremely tight, with a Ki value well below 0.1 nM. The stability of the angiogenin-PRI complex was assessed by cation-exchange HPLC quantitation of free angiogenin. No significant dissociation was detected after 17 hr at 25 degrees C in the presence of a large excess of bovine ribonuclease, which serves as a scavenger for free inhibitor. The results of these experiments, based on the predictive capacity of the angiogenin/RNase homology, suggest that PRI and related inhibitors may participate in the in vivo regulation of angiogenin and that this might have pharmacologic and/or therapeutic implications.
Shapiro
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Vallee
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D000482:Allantois / Q000187:drug effects; D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors*; D000818:Animals; D002642:Chick Embryo; D002823:Chorion / Q000187:drug effects; D006131:Growth Inhibitors; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010926:Placental Hormones / Q000494:pharmacology*; D012335:RNA, Ribosomal; D012259:Ribonuclease, Pancreatic / Q000037:antagonists & inhibitors; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity
D043925:Angiogenesis Inducing Agents; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D010926:Placental Hormones; D012335:RNA, Ribosomal; C022052:placental ribonuclease inhibitor; D012260:Ribonucleases; C046366:angiogenin; D012259:Ribonuclease, Pancreatic