Simple shifts in redox/thiol balance that perturb blood coagulation.
The biological chemistry that underlies and regulates the blood coagulation cascade is not fully understood. To begin to understand this, we performed clotting assays under various redox conditions. By varying the amount of oxidant and/or antioxidant in these assays, we observed that both the intrinsic/tenase complex and the extrinsic pathways were susceptible to shifts in the thiol/redox balance. We established a dichotomy where blood clotting via the intrinsic pathway was sensitive to oxidation whereas the tissue factor or extrinsic pathway was more sensitive to reduction. These differential inhibitory effects present a conceptual mechanism for selective modulation of the activities of clotting factors specific for the respective pathways. These data also suggest that blood clotting may be influenced by unidentified redox or thiol equilibria.
Bayele
Henry K
HK
Department of Haematology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF, UK. h.bayele@rfc.ucl.ac.uk
Murdock
Paul J
PJ
Perry
David J
DJ
Pasi
K John
KJ
D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005337:Fibrin / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D019803:Glutathione Disulfide / Q000494:pharmacology; D006801:Humans; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010314:Partial Thromboplastin Time; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D016877:Oxidants; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D005337:Fibrin; D004228:Dithionitrobenzoic Acid; D005978:Glutathione; D019803:Glutathione Disulfide