Effect of Nitric Oxide on Platelet Progeneitor Growth, Posttranslational Modification of Protein, and Function

Abstract

Abstract: Nitric oxide (NO), formed through the action of nitric oxide synthase of platelets, which upon exposure to oxy-gen-free radical forming peroxynitrite, could be involved in posttranslational modification of platelet intra- and extracellu-lar proteins. Platelet proteins modified through nitrotyrosylation and the S-nitrosylation can play very important roles in controlling platelet function. Keywords: Nitric oxide, platelet aggregation, platelet, nitrotyrosylation. INTRODUCTION Platelets play an important role in hemostasis and throm-bosis. Following injury to blood vessels and in certain patho-logic conditions, platelets adhere to the exposed sub-endothelial connective tissue, particularly to collagen, before aggregating and releasing several biologically active sub-stances. Many factors appear to modulate adherence of plate-lets to the exposed collagen and the ensuing aggregation process, but the precise sequence of events that leads to ag-gregation and the release reaction has not been firmly estab-lished. The interactions of platelets with vessel wall matrices have been the primary focus of numerous studies. Platelets possess many receptors including integrin and non-integrin receptors that interact with matrix type I collagen and type III collagen. Nitric oxide synthase (NOS) catalyzes the conversion of arginine to citrulline and nitric oxide (NO). There are three known isoforms of nitric oxide, inducible (iNOS), neural (nNOS) and endothelial (eNOS). It is well documented that platelets contain eNOS although the presence of nNOS has also been reported. Nitric oxide (NO) has also been reported to be involved in the collagen-platelet interactive process [1]. The role of NO in cellular signaling has become one of the most rapidly growing areas in biology. In many instances NO mediates its biological effects by activating guanylyl cyclase and increasing the cyclic 3’, 5’-guanosine mono-phosphate (cGMP) content of cells. Before the recognition of NO as an endogenously produced signal transducer, others and we had reported that collagen causes platelets to gener-ate the cGMP and that dibutyryl cyclic 3’, 5’-guanosine mo-nophosphate enhances platelet aggregation in the presence of sub-threshold amounts of collagen [2]. Interestingly, the generation of NO occurs only upon stimulation of platelets with collagen, but not with ADP or thrombin [2, 3]. We cor-roborate that collagen stimulated platelet aggregation results in the generation of NO by the platelets themselves.