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

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.

• Authors: Roberta Mastrantonio, Manuela Cervelli, Stefano Pietropaoli, Paolo Mariottini, Marco Colasanti, Tiziana Persichini
• Journal: PloS one (PLoS One) Vol. 11 Issue 2 Pg. e0149802 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 26895301 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Receptors, N-Methyl-D-Aspartate
• tat Gene Products, Human Immunodeficiency Virus
• Oxidoreductases Acting on CH-NH Group Donors
• polyamine oxidase

Topics

• Antioxidant Response Elements
• Antioxidants (metabolism)
• Cell Line, Tumor
• Gene Expression Regulation
• Humans
• NF-E2-Related Factor 2 (metabolism)
• Neuroblastoma
• Oxidative Stress (genetics)
• Oxidoreductases Acting on CH-NH Group Donors (metabolism)
• Receptors, N-Methyl-D-Aspartate (metabolism)
• tat Gene Products, Human Immunodeficiency Virus (physiology)