Redox control of platelet function.
There has recently been a dramatic expansion in research in the area of redox biology with systems that utilize thiols to perform redox chemistry being central to redox control. Thiol-based reactions occur in proteins involved in platelet function, including extracellular platelet proteins. The alphaIIbbeta3 fibrinogen receptor contains free thiols that are required for the activation of this receptor to a fibrinogen-binding conformation. This process is under enzymatic control, with protein disulfide isomerase playing a central role in the activation of alphaIIbbeta3. Other integrins, such as the alpha2beta1 collagen receptor on platelets, are also regulated by protein disulfide isomerase and thiol metabolism. Low molecular weight thiols that are found in blood regulate these processes by converting redox sensitive disulfide bonds to thiols and by providing the appropriate redox potential for these reactions. Additional mechanisms of redox control of platelets involve nitric oxide that inhibits platelet responses, and reactive oxygen species that potentiate platelet thrombus formation. Specific nitrosative or oxidative modifications of thiol groups in platelets may modulate platelet function. Since many biologic processes are regulated by redox reactions that involve surface thiols, the extracellular redox state can have an important influence on health and disease status and may be a target for therapeutic intervention.
Essex
David W
DW
Department of Medicine and the Sol Sherry Thrombosis Research Center, Philadelphia, Pennsylvania 19140, USA. david.essex@temple.edu
D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D006801:Humans; D010084:Oxidation-Reduction; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001798:Blood Proteins; D013438:Sulfhydryl Compounds; C496931:PDIA6 protein, human; D019704:Protein Disulfide-Isomerases