1. Nitric Oxide: News from Stem Cells to Platelets
- Author
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S. Negrotto, María Albertina Romaniuk, M. Schattner, Pozner Rg, Lina Paola D'Atri, and E. Malaver
- Subjects
Blood Platelets ,CIENCIAS MÉDICAS Y DE LA SALUD ,Cellular differentiation ,Medicina Clínica ,Biology ,Nitric Oxide ,Biochemistry ,Paracrine signalling ,MEGAKARYOCYTES ,Drug Discovery ,medicine ,STATINS ,Animals ,Humans ,Thrombopoiesis ,Autocrine signalling ,Pharmacology ,CGMP ,NO-NSAID ,Organic Chemistry ,Hematopoietic stem cell ,Hematopoietic Stem Cells ,PLATELETS ,APOPTOSIS ,medicine.anatomical_structure ,Second messenger system ,Molecular Medicine ,Medicina Critica y de Emergencia ,Nitric Oxide Synthase ,Stem cell ,Soluble guanylyl cyclase ,NITRIC OXIDE ,STEM CELLS - Abstract
Nitric oxide (NO) is a diffusible, short-lived, diatomic free radical ubiquitously produced by mammalian cells. The generation of NO from L-arginine is enzymatically regulated by three different isoforms of NO synthases. The NO signaling pathway involves mainly the activation of soluble guanylyl cyclase to produce cyclic GMP (cGMP) as a second messenger and downstream mediator. In addition, the free radical activity of NO can cause cellular damage through a phenomenon known as nitrosative stress. NO is a pleiotropic biomodulator in several systems, including the cardiovascular, nervous and immune systems. In the hematopoietic system, NO is thought to be an autocrine or paracrine messenger but also an intracellular effector molecule. Megakaryopoiesis and subsequent thrombopoiesis occur through complex biologic steps that involve hematopoietic stem cell commitment to megakaryocytic lineage, megakaryocyte maturation and finally, platelet release. Here, we summarize the current knowledge regarding the role of exogenous and endogenous NO in hematopoietic stem cell biology, megakaryocyte development and platelet biogenesis as well as relevance of platelet-derived NO generation on platelet function. Dysregulation of NO synthesis has been observed in several diseases, and the evaluation of a series of pharmacological agents with the ability to modulate the NO/ cGMP pathway in platelets will also be discussed. Fil: D'Atri, Lina Paola. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Malaver Marín, Elisa. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Romaniuk, María Albertina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pozner, Roberto Gabriel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Negrotto, Soledad. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schattner, Mirta Ana. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Hemostasia y Trombosis; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
- Published
- 2009