Title:Cross-Talk Between NO Synthase Isoforms in Neuro-Inflammation: Possible Implications in HIV-Associated Neurocognitive Disorders
Volume: 23
Issue: 24
Author(s): Tiziana Persichini, Sofia Mariotto, Hisanori Suzuki, Elena Butturini, Roberta Mastrantonio, Orazio Cantoni, Marco Colasanti
Affiliation:
关键词:
花生四烯酸，星形胶质细胞，一氧化氮合酶，磷脂酶A2，一氧化氮，一方面，HIV，诱导型NOS。
摘要: 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 Ca2+-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.
