Genes endothelial constitutive nitric-oxide

FIGURE 4 Potential trans-acting factor binding sites in the 5 -flanking region of the human endothelial constitutive nitric oxide synthase gene. Nucleotides are numbered relative to the major transcriptional start site ( + 1). See text for details. 

Ohata, T. et al. 1998. Hybrid artificial lung with interleukin-10 and endothelial constitutive nitric oxide synthase gene transfected endotheUal cells attenuates inflammatory reactions induced by cardiopulmonary bypass. Circulation 98 11269-74. 

The enzyme nitric oxide synthase (NOS), that produces NO and citrullin from arginine, occurs as several isoenzymes (Knowles et al., 1989). Type I NOS is a constitutive, calcium and calmodulin-dependent enzyme, present in neurons and, possibly, in glia. Type II NOS is calcium-independent and can be induced in macrophages and glial cells by exposure to bacterial lipopolysaccharide (Galea et al., 1992 Murphy et al., 1993). Type III NOS is the endothelial iso-enzyme. NOS-I, II and III are produced by diflferent genes (Bredt et al., 1991 Lamas et al., 1992 Xie et al., 1992 Lowenstein et al., 1992 Lyons et al. 1992 Ogura et al., 1993). NOS displays NADPH-dependent diaphorase... 

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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