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Identification of divalent metal ion-dependent inhibition of activated protein-C by alpha-2-macroglobulin and alpha-2-antiplasmin in blood and comparisons to inhibition of factor-Xa, thrombin, and plasmin

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Overview

authors

  • Heeb, Mary Jo
  • Gruber, A.
  • Griffin, John

publication date

  • 1991

journal

  • Journal of Biological Chemistry  Journal

abstract

  • The half-life of activated protein C (APC) was 31 min in citrated blood and 18 min in whole blood. Immunoblotting analysis of citrated blood identified APC-protein C inhibitor (APC-PCI) and APC-alpha 1-antitrypsin complexes. Whole blood contained two additional APC-inhibitor complexes, one stimulated by Ca2+ and another by Mg2+. The former was identified as APC-alpha 2-macroglobulin (APC-alpha 2M) while the latter was not identified. APC-alpha 2-antiplasmin complexes (APC-alpha 2AP) were identified, comigrating with APC-PCI complexes. Purified alpha 2M and alpha 2AP inhibited APC in the presence of Ca2+ (k2 = 99 and 100 M-1 S-1, respectively. Inhibition of APC and Factor Xa by alpha 2M and inhibition of APC by alpha 2AP was stimulated by Ca2+, Mn2+, and Mg2+. Inhibition of thrombin by alpha 2M and of plasmin by alpha 2AP was not altered by EDTA or Ca2+, suggesting divalent metal ions affect APC and Factor Xa rather than the inhibitors. k2 values for the APC inhibitors and their plasma concentrations suggest that PCI and alpha 1-antitrypsin are the more important APC inhibitors and that alpha 2M and alpha 2AP are metal ion-dependent auxiliary inhibitors. Inhibitors can account for the in vivo half-life of APC.

subject areas

  • Enzyme Activation
  • Factor Xa Inhibitors
  • Fibrinolysin
  • Half-Life
  • Humans
  • Immunoblotting
  • In Vitro Techniques
  • Kinetics
  • Metals
  • Protein C
  • Thrombin
  • alpha-2-Antiplasmin
  • alpha-Macroglobulins
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Identity

International Standard Serial Number (ISSN)

  • 0021-9258

PubMed ID

  • 1716632
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Additional Document Info

start page

  • 17606

end page

  • 17612

volume

  • 266

issue

  • 26

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