Nitric-oxide synthases cellular mechanisms

The production of NO in vascular endothelium as well as in other cell types is catalyzed by the enzyme nitric oxide synthase (NOS). Three different classes of NOS have been described through cloning techniques and other approaches (1) an endothelial form of NOS whose activity is stimulated by the binding of the Ca2+-calmodulin complex upon cellular activation of Ca2+ mobilization (2) a neural form of NOS whose activation is through a similar mechanism (i.e., intracellular Ca2+ mobilization) but whose properties are distinct from the endothelial enzyme and (3) an in-... 

ABSTRACT In mammals, nitric oxide (NO) is a reactive free radical involved in diverse physiological functions. NO and its redox-related forms NO+ and NO react with di(oxygen) and its derivatives, with metalloproteins and thiol-containing proteins. NO-mediated nitrosation of proteins represents an important cellular regulatory mechanism. Biosynthesis of NO is catalysed by nitric oxide synthase (NOS). Three isoenzymes representing distinct gene products have been identified the inducible NOS isoform, the constitutive neuronal and endothelial isoforms. Inducible and constitutive NOSs have the same structural features, but their activities differ in their dependence to calcium and the rate of NO produced. The principal NO-mediated functions in mammals are endothelium-dependent relaxation, neurotransmission and immune response. The role of NO in the antitumor immune response comprises both regulatory and effector functions at the intra- or inter-cellular level. The first function includes inhibition of lymphocyte proliferation or participation in different transduction pathways. The second fiinction includes pro- or anti-tumoral effects and NO-mediated cell toxicity or cell resistance to apoptosis. 

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