HIV-1 gp120 induces antioxidant response element-mediated expression in primary astrocytes: Role in HIV associated neurocognitive disorder

• Published in: Neurochemistry international 2012-10, Vol.61 (5), p.807-814
• Main Authors: Reddy, Pichili Vijaya Bhaskar, Gandhi, Nimisha, Samikkannu, Thangavel, Saiyed, Zainulabedin, Agudelo, Marisela, Yndart, Adriana, Khatavkar, Pradnya, Nair, Madhavan P.N.
• Format: Article
• Language: English
• Subjects: AIDS Dementia Complex - metabolism; AIDS Dementia Complex - virology; Antioxidant Response Elements - physiology; Antioxidants; Apoptosis; Astrocytes; Astrocytes - metabolism; Biological and medical sciences; Brain; Calcium (intracellular); Cell death; Cell survival; Cells, Cultured; Central nervous system; Chelating agents; Cognition; Defense mechanisms; Depression; Envelope protein; Enzymes; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Viral; Glycoprotein gp120; Hand; Hemoxygenase; HIV Envelope Protein gp120 - physiology; HIV-1 gp120; Human immunodeficiency virus 1; Humans; Infection; Leucine zipper proteins; NAD(P)H dehydrogenase; NAD(P)H dehydrogenase (quinone); NAD(P)H dehydrogenase quinone1; Neuropathogenesis; Neurotoxicity; NF-E2-Related Factor 2 - biosynthesis; NF-E2-Related Factor 2 - physiology; Nrf2; Oxidative stress; Oxidative Stress - physiology; Transcription factors; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2011.06.011

► HIV-1 gp120 upregulates second phase antioxidant defensive enzymes. ► Antioxidants and calcium chelator blocked the upregulation of Nrf2, HO-1 and Nqo1. ► Oxidative stress and calcium play a role in Nrf2 mediated events. HIV infection affects the central nervous system resulting in HIV associated neurocognitive disorder (HAND), which is characterized by depression, behavioral and motor dysfunctions. The HIV-1 viral envelope protein gp120 is known to induce the release of neurotoxic factors which lead to apoptotic cell death. Although the exact mechanisms involved in HIV-1 gp120-induced neurotoxicity are not completely understood, oxidative stress is suggested to play a vital role in the neuropathogenesis of HAND. Astrocytes represent major population of the non-neuronal cell type in the brain and play a critical role in the neuropathogenesis of HAND. Increased oxidative stress is known to induce nuclear factor erythroid derived 2-related factor 2 (Nrf2), a basic leucine zipper transcription factor which is known to regulate the antioxidant defensive mechanism. However, the role of Nrf2 in HAND has not been elucidated. We report that gp120 significantly upregulates Nrf2 in human astrocytes and is associated with stimulation of key antioxidant defensive enzymes Hemoxygenase (HO-1) and NAD(P)H dehydrogenase quinone1 (Nqo1). Pretreatment of the astrocytes with antioxidants or a specific calcium chelator BAPTA-AM, significantly blocked the upregulation of Nrf2, HO-1 and Nqo1. These results suggest a possible role of the intracellular calcium and oxidative stress in Nrf2 mediated antioxidant defense mechanism, which may have protective role in promoting cell survival.