Comparison of the effect of histidine-rich glycoprotein and 6-aminohexanoic acid on plasmin production and fibrinolysis in vitro.
Because histidine-rich glycoprotein binds to the kringle 1-3 domain of plasminogen, it may affect fibrinolysis by reducing fibrin-dependent plasmin production, and in this way it could be mechanistically analogous to 6-aminohexanoic acid. We tested this hypothesis by comparing the effects of histidine-rich glycoprotein and 6-aminohexanoic acid in an in vitro assay of fibrin-dependent plasmin production mediated by tissue plasminogen activator. Whereas 1 mM of 6-aminohexanoic acid increased the K(m) of the reaction from approximately 0.22 microM to approximately 1.7 microM, 2 microM of histidine-rich glycoprotein had no discernible effect. Similar results were obtained in an assay based upon fibrin clot lysis. Therefore, we could not document an effect of histidine-rich glycoprotein on the rate of fibrin-dependent plasmin production.
Horne
M K
MK
Hematology Service, Clinical Pathology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. mhorne@nih.gov
Goad
J L
JL
Merryman
P K
PK
Cullinane
A M
AM
D015119:Aminocaproic Acid / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D005341:Fibrinolysin / Q000096:biosynthesis* / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects*; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012685:Sepharose / Q000378:metabolism
D000933:Antifibrinolytic Agents; D006023:Glycoproteins; D006639:Histidine; D010958:Plasminogen; D012685:Sepharose; D005341:Fibrinolysin; D015119:Aminocaproic Acid