Platelet receptor redox regulation.
Several recent findings point to an important role for redox regulation of platelet responses to collagen involving the receptor, glycoprotein (GP)VI. First, the antioxidant dietary compound, quercetin, was shown to inhibit GPVI-dependent platelet activation and signaling responses to collagen. Second, collagen increased platelet production of the oxygen radical, superoxide anion (O2-), mediated by the multi-subunit enzyme nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidase. In that case, O2- was implicated in regulating not initial aggregation, but collagen-induced thrombus stabilization involving release of ADP. Third, our laboratory showed that an unpaired thiol in the GPVI cytoplasmic tail undergoes rapid oxidation to form GPVI homodimers following ligand binding, preceding GPVI signaling and ectodomain metalloproteolysis, and indicating formation of an oxidative submembranous environment in activated platelets. This review examines receptor/redox regulation in other cells, and relevance to the pathophysiological function of GPVI and other platelet receptors initiating thrombus formation in haemostasis or thrombotic diseases such as heart attack and stroke.
Arthur
Jane F
JF
Department of Immunology, Monash University, Alfred Medical Research & Education Precinct, Melbourne 3004, Victoria, Australia.
Gardiner
Elizabeth E
EE
Kenny
Dermot
D
Andrews
Robert K
RK
Berndt
Michael C
MC
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D019281:Dimerization; D006331:Heart Diseases / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D010084:Oxidation-Reduction; D010974:Platelet Aggregation; D017434:Protein Structure, Tertiary; D011794:Quercetin / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism
D000975:Antioxidants; D018955:CD36 Antigens; D013481:Superoxides; D000244:Adenosine Diphosphate; D003094:Collagen; D011794:Quercetin; D019255:NADPH Oxidases