TAILIEUCHUNG - Báo cáo khoa học: Nitric oxide and cell proliferation

Nitric oxide (NO • ) has been proposed to be a physiological modulator of cell proliferation, able to promote in most cases cell cycle arrest. In this review I explore the molecular basis of this mechanism of action. The mod-ulatory action of NO • on the intracellular concentration of cGMP and the machinery directly involved in the control of cell cycle progression, inclu-ding the expression and activity of diverse cyclins and cyclin-dependent kinases, | FEBS Journal REVIEW ARTICLE Nitric oxide and cell proliferation Antonio Villalobo Institute de Investigaciones Biomedicas Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid Spain Keywords cell cycle nitric oxide synthase nitrosative stress signalling S-nitrosylation Correspondence A. Villalobo Instituto de Investigaciones Biomedicas Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid c Arturo Duperier 4 E-28029 Madrid Spain Fax 34 91 585 4401 Tel 34 91 585 4424 E-mail Received 3 March 2006 accepted 30 March 2006 Nitric oxide NO has been proposed to be a physiological modulator of cell proliferation able to promote in most cases cell cycle arrest. In this review I explore the molecular basis of this mechanism of action. The modulatory action of NO on the intracellular concentration of cGMP and the machinery directly involved in the control of cell cycle progression including the expression and activity of diverse cyclins and cyclin-dependent kinases their physiological inhibitors and the master transcriptional regulator retinoblastoma protein will be discussed. The role of NO in proliferation mediated by tyrosine kinase receptors such as the epidermal growth factor receptor and downstream signalling pathways will also be considered. Finally the involvement of NO in proliferative processes relevant for normal development will be outlined. doi Introduction Nitric oxide NO is a highly reactive gas universally produced by organisms distributed across all phyla ranging from bacteria to human and exerting a myriad of biological functions. The discovery of new targets of NO as physiological regulators of multiple vital functions in vertebrates has surpassed our expectations of the versatility of the actions of this biological messenger which was first recognized because of its relevant participation in major functions including the control of vascular tone

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