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.

Capone, C., Cervelli, M., Angelucci, E., Colasanti, M., Macone, A., Mariottini, P., et al. (2013). A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity. FREE RADICAL BIOLOGY & MEDICINE, 63C:, 99-107 [10.1016/j.freeradbiomed.2013.05.007].

A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity

CERVELLI, MANUELA;COLASANTI, Marco;MARIOTTINI, Paolo;PERSICHINI, TIZIANA
2013-01-01

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.
2013
Capone, C., Cervelli, M., Angelucci, E., Colasanti, M., Macone, A., Mariottini, P., et al. (2013). A role for spermine oxidase as a mediator of reactive oxygen species production in HIV-Tat-induced neuronal toxicity. FREE RADICAL BIOLOGY & MEDICINE, 63C:, 99-107 [10.1016/j.freeradbiomed.2013.05.007].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/267497
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