title: Cross-Talk Between NO Synthase Isoforms in Neuro-Inflammation: Possible Implications in HIV-Associated Neurocognitive Disorders.
abstract: Inducible nitric oxide synthase (iNOS) is expressed in several cell types, particularly in inflammatory cells, in response to diverse proinflammatory stimuli, including viral proteins as HIV Tat and gp120. This response is preceded by an early decline in basal nitric oxide (NO) levels, dependent on a signaling leading to inhibition of the constitutive isoform of NO synthase (cNOS). This process requires critical levels of arachidonic acid (AA), generated by Ca&lt;sup&gt;2+&lt;/sup&gt;-dependent activation of cytosolic phospholipase A2, and is mediated by the downstream tyrosine kinase-dependent phosphorylation of cNOS. Lowering basal NO levels are necessary for the activation of nuclear factor-κB, and thus for the expression of a variety of genes regulated by this transcription factor, which include iNOS. Notably, NO and AA, two small lipid soluble molecules, can trigger the above responses also in distal cells. Thus, AA produced at the very early stages of the inflammatory response is a likely critical signal switching the regulation of the "NO tone" from physiological (i.e., mediated by cNOS) to pathological (i.e., mediated by iNOS). This later phase of the inflammatory response is often accompanied by the onset of deleterious effects in the tissue, in which a critical role is played by iNOS-derived NO (directly or indirectly, i.e., via formation of peroxynitrite) as well as by products of the AA cascade. In this review, the authors discuss the implications of the crosstalk between the NOS isoforms in HIV-associated neuro-pathogenesis highlighting the role of NO and AA as mediators of cytotoxicity.
authors: Department of Sciences, University Roma Tre, Rome, Italy.
authors: Tiziana
authors: T
authors: Persichini
authors: Sofia
authors: S
authors: Mariotto
authors: Hisanori
authors: H
authors: Suzuki
authors: Elena
authors: E
authors: Butturini
authors: Roberta
authors: R
authors: Mastrantonio
authors: Orazio
authors: O
authors: Cantoni
authors: Marco
authors: M
authors: Colasanti
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism; D006678:HIV / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D006801:Humans; D007249:Inflammation; D016328:NF-kappa B / Q000378:metabolism; D019965:Neurocognitive Disorders / Q000209:etiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D016328:NF-kappa B; D020033:Protein Isoforms; D054322:tat Gene Products, Human Immunodeficiency Virus; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase