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HIV-Tat Induces the Nrf2/ARE Pathway Through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells

HIV-Tat Induces the Nrf2/ARE Pathway Through NMDA Receptor-Elicited Spermine Oxidase Activation in Human Neuroblastoma Cells

Roberta Mastrantonio, Manuela Cervelli, Stefano Pietropaoli, Paolo Mariottini, Marco Colasanti, Tiziana Persichini

PLoS One. 2016 Feb 19;11(2):e0149802.

PMID: 26895301

Abstract:

Previously, we reported that HIV-Tat elicits spermine oxidase (SMO) activity upregulation through NMDA receptor (NMDAR) stimulation in human SH-SY5Y neuroblastoma cells, thus increasing ROS generation, which in turn leads to GSH depletion, oxidative stress, and reduced cell viability. In several cell types, ROS can trigger an antioxidant cell response through the transcriptional induction of oxidative stress-responsive genes regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2). Here, we demonstrate that Tat induces both antioxidant gene expression and Nrf2 activation in SH-SY5Y cells, mediated by SMO activity. Furthermore, NMDAR is involved in Tat-induced Nrf2 activation. These findings suggest that the NMDAR/SMO/Nrf2 pathway is an important target for protection against HIV-associated neurocognitive disorders.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4249502	NMDA Receptor NR2BCT(1292-1304)-TAT			Price

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