title: A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity.
abstract: Chronic oxidative stress, which occurs in brain tissues of HIV-infected patients, is involved in the pathogenesis of HIV-associated dementia. Oxidative stress can be induced by HIV-1-secreted proteins, either directly or indirectly through the release of cytotoxic factors. In particular, HIV-1 Tat is able to induce neuronal death by interacting with and activating the polyamine-sensitive subtype of the NMDA receptor (NMDAR). Here, we focused on the role of polyamine catabolism in Tat-induced oxidative stress in human neuroblastoma (SH-SY5Y) cells. First, Tat was found to induce reactive oxygen species production and to affect cell viability in SH-SY5Y cells, these effects being mediated by spermine oxidase (SMO). Second, Tat was observed to increase SMO activity as well as decreasing the intracellular spermine levels. Third, Tat-induced SMO activation was completely prevented by the NMDAR antagonist MK-801, clearly indicating an involvement of NMDAR stimulation. Finally, pretreatment of cells with N-acetylcysteine, a scavenger of H₂O₂, and with MK-801 was able to completely inhibit reactive oxygen species formation and to restore cell viability. Altogether, these data strongly suggest a role for polyamine catabolism-derived H₂O₂ in neurotoxicity as elicited by Tat-stimulated NMDAR.
authors.affiliation: Department of Science, University Roma Tre, 00146 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Capone
authors.forename: Manuela
authors.initials: M
authors.lastname: Cervelli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Angelucci
authors.forename: Marco
authors.initials: M
authors.lastname: Colasanti
authors.forename: Alberto
authors.initials: A
authors.lastname: Macone
authors.forename: Paolo
authors.initials: P
authors.lastname: Mariottini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Persichini
mesh_terms: D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002460:Cell Line; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D000097667:Polyamine Oxidase
chemical_list: D006861:Hydrogen Peroxide; D009419:Nerve Tissue Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D013096:Spermine; D054322:tat Gene Products, Human Immunodeficiency Virus; D000097667:Polyamine Oxidase; C485668:GRIN1 protein, human
keywords: CHL; Free radicals; Glutathione; HAD; HAND; HIV-1 Tat; HIV-associated dementia; HIV-associated neurocognitive disorders; L-NAME; MDL; N(1), N(4)-bis(2,3-butadienyl)-1,4-butanediamine; N(ω)-Nitro-L-arginine methyl ester hydrochloride; N-acetylcysteine; N-methyl-d-aspartate; N-methyl-d-aspartate receptor; NAC; NMDA; NMDA receptor; NMDAR; Oxidative stress; ROS; Reactive oxygen species; SH-SY5Y cells; SMO; Spd; Spermine oxidase; Spm; chlorhexidine digluconate; reactive oxygen species; spermidine; spermine; spermine oxidase