title: The role of arachidonic acid in the regulation of nitric oxide synthase isoforms by HIV gp120 protein in astroglial cells.
abstract: HIV-associated neurocognitive disorder (HAND) is a common cognitive impairment in AIDS that affects 15 to 50% of adults infected with human immunodeficiency virus (HIV). Excessive amounts of nitric oxide (NO), as produced by inducible NO synthase (iNOS) upon exposure of activated microglia and astrocytes to cytokines and/or viral proteins (e.g., HIV tat and gp120), are assumed to contribute to neuronal abnormalities in HAND. Evidence exists supporting the notion that iNOS induction takes place after an early decline in physiological NO levels (i.e., NO released by constitutive NOS). Here, we demonstrate that HIV-1 gp120 is able to inhibit neuronal NOS through a cytosolic phospholipase A2 (cPLA2)-dependent arachidonic acid (AA) production, this response being critical for allowing activation of the transcriptional factor NF-κB and subsequent iNOS and interleukin-1β transcription in astroglial cells. In this context, AA seems to act as an upstream proinflammatory effector. In view of the pathogenic role of cPLA2 in HAND, a deeper insight into the molecular and cellular mechanisms of its modulation may be helpful in finding new drugs to manage cognitive impairment in HIV-1 patients.
authors: Department of Sciences, University Roma Tre, Rome 00146, Italy. Electronic address: tiziana.persichini@uniroma3.it.
authors: Tiziana
authors: T
authors: Persichini
authors: Department of Sciences, University Roma Tre, Rome 00146, Italy.
authors: Roberta
authors: R
authors: Mastrantonio
authors: Department of Sciences, University Roma Tre, Rome 00146, Italy.
authors: Silvia
authors: S
authors: Del Matto
authors: Department of Biomolecular Science, University of Urbino "Carlo Bo," 61029 Urbino PU, Italy.
authors: Letizia
authors: L
authors: Palomba
authors: Department of Biomolecular Science, University of Urbino "Carlo Bo," 61029 Urbino PU, Italy.
authors: Orazio
authors: O
authors: Cantoni
authors: Department of Sciences, University Roma Tre, Rome 00146, Italy.
authors: Marco
authors: M
authors: Colasanti
mesh_terms: D015526:AIDS Dementia Complex / Q000235:genetics / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism* / Q000821:virology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D015699:HIV Envelope Protein gp120; D053583:Interleukin-1beta; D007527:Isoenzymes; D016328:NF-kappa B; C514793:gp120 protein, Human immunodeficiency virus 1; D016718:Arachidonic Acid; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D054467:Phospholipases A2
keywords: Arachidonic acid; Astroglial cells; Cytosolic phospholipase A(2); Free radicals; HIV gp120; Interleukin-1β; Nitric oxide