Platelet regulation by NO/cGMP signaling and NAD(P)H oxidase-generated ROS.
Platelets play a crucial role in the physiology of primary hemostasis and pathophysiological processes such as arterial thrombosis. Accumulating evidence suggests a key regulatory role of both NO and reactive oxygen species (ROS) in platelets. While the inhibitory role of NO/cGMP signaling in both murine and human platelets is well established, recent data suggest that intracellular ROS generation is involved in platelet activation. Thrombin-induced intracellular ROS production was inhibited by NAD(P)H oxidase inhibitors (DPI and apocynin), cyclooxygenase inhibitor (acetylsalicylic acid), and superoxide scavengers (tiron and MnTMPyP). Furthermore, thrombin (Trap6)-induced platelet aggregation and thrombus formation on collagen under high shear was inhibited by NAD(P)H oxidase inhibitors (DPI and apocynin), whereas secretion and platelet shape change were not affected. Inhibition of alphaIIbbeta3 activation by NAD(P)H oxidase inhibitors and superoxide scavengers was independent of NO/cGMP signaling demonstrating a direct role of platelet NAD(P)H oxidase-generated ROS for integrin alphaIIbbeta3 activation.
Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, 97080 Wuerzburg, Germany.
Antonija J
AJ
Begonja
Lino
L
Teichmann
Jörg
J
Geiger
Stepan
S
Gambaryan
Ulrich
U
Walter
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013917:Thrombin; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017382:Reactive Oxygen Species; D000098662:Vasodilator-Stimulated Phosphoprotein; D009569:Nitric Oxide; D019255:NADPH Oxidases; D013917:Thrombin; D006152:Cyclic GMP