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

• DOI: 10.1371/journal.pone.0149802
• Publication Date: 2016-02-19T13:49:19Z
• Authors: Roberta Mastrantonio; Manuela Cervelli; Stefano Pietropaoli; Paolo Mariottini; Marco Colasanti; Tiziana Persichini
• Keywords: oxidative stress, nrf2, hiv tat; 0301 basic medicine; Oxidoreductases Acting on CH-NH Group Donors; 0303 health sciences; NF-E2-Related Factor 2; Science; Q; R; Receptors, N-Methyl-D-Aspartate; Antioxidant Response Elements; Antioxidants; 3. Good health; Neuroblastoma; Oxidative Stress; 03 medical and health sciences; Gene Expression Regulation; Cell Line, Tumor; Polyamine Oxidase; Medicine; Humans; tat Gene Products, Human Immunodeficiency Virus; Research Article

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 turn leads to GSH depletion, oxidative stress, and reduced cell viability. In several types, can trigger an antioxidant response the transcriptional induction of stress-responsive genes regulated by nuclear factor erythroid 2-related 2 (Nrf2). Here, demonstrate Tat induces both gene expression Nrf2 activation mediated SMO activity. Furthermore, NMDAR is involved Tat-induced activation. These findings suggest NMDAR/SMO/Nrf2 pathway important target for protection against HIV-associated neurocognitive disorders.