Modulation of protein C inhibitor activity by histidine-rich glycoprotein and platelet factor 4: role of zinc and calcium ions in the heparin-neutralizing ability of histidine-rich glycoprotein.
Effects of zinc and calcium ions on the heparin-neutralizing abilities of histidine-rich glycoprotein (HRG) and platelet factor 4 (PF4) were examined. Both HRG and PF4 effectively neutralized the ability of heparin to accelerate the activated protein C (APC) and the thrombin inhibitions by protein C inhibitor (PCI). the heparin-neutralizing ability of HRG in the APC inhibition by PCI, however, was decreased in a Ca(2+)-dependent manner and apparently lost at 1 mM Ca2+, while it was enhanced by Zn2+ regardless of the presence or absence of Ca2+. The heparin-neutralizing ability of HRG in the thrombin inhibition by PCI was not affected by Ca2+. In contrast to HRG, there was no significant difference in the heparin-neutralizing ability of PF4 in the presence or absence of 1 mM Ca2+. These results strongly suggest additional physiological functions of HRG and PF4 as modulators of PCI.
Kazama
Y
Y
Department of Biochemistry, Niigata University School of Medicine, Japan.
Koide
T
T
D002118:Calcium / Q000378:metabolism; D006494:Heparin Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015849:Plasminogen Inactivators / Q000378:metabolism*; D010978:Platelet Factor 4 / Q000494:pharmacology*; D011486:Protein C / Q000037:antagonists & inhibitors / Q000378:metabolism; D018046:Protein C Inhibitor; D011506:Proteins / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors; D015032:Zinc / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
D006494:Heparin Antagonists; D015849:Plasminogen Inactivators; D011486:Protein C; D018046:Protein C Inhibitor; D011506:Proteins; D000099053:Histidine-Rich Glycoprotein; D010978:Platelet Factor 4; D013917:Thrombin; D015032:Zinc; D002118:Calcium