| Inhibition of Nuclear Factor Erythroid 2-Related Factor 2 Exacerbates HIV-1 gp120-Induced Oxidative and Inflammatory Response: Role in HIV Associated Neurocognitive Disorder. | |
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MedLine Citation:
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PMID: 22528837 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The HIV epidemic continues to be the most severe public health problem and concern within USA and across the globe. In spite of the highly active antiretroviral therapy, HIV infected subjects experience major neurological complications that range from HIV associated dementia to moderate neurocognitive and motor impairments collectively termed as HIV associated neurocognitive disorders (HAND). Astrocytes play an important role in the neuropathogenesis of HAND. Further, in the recent years it has been shown that oxidative stress plays a major role in the neuropathogenesis of HAND. Nuclear factor erythroid 2-related factor 2 (Nrf2), a leucine zipper redox-sensitive transcription factor, is an important regulator of cell survival and adaptive mechanisms and has been shown to possess a protective role in a variety of neurological and inflammatory disorders. Earlier we have shown that Nrf2 is upregulated in response to HIV-1 gp120 and such upregulation of Nrf2 may be a protective mechanism against the HIV-induced oxidative stress. We hypothesize that Nrf2-mediated antioxidant pathways are important in regulating the HIV-induced oxidative stress and that the disruption of Nrf2 makes the cells more susceptible to HIV gp120-induced deleterious effects. Our results indicate that when astrocytes are exposed to gp120 there is an increase in the expression of NOX2, a subunit of NADPH oxidase, and also an upregulated expression of nuclear factor kappa B, tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9). However, the degree of expression was significantly higher in those cells where Nrf2 was silenced by siRNA. Taken together, these results suggest a possible protective role of Nrf2 in regulating the levels of pro-oxidative and pro-inflammatory molecules in HAND. |
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Authors:
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Pichili Vijaya Bhaskar Reddy; Marisela Agudelo; Venkata S R Atluri; Madhavan P Nair |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-25 |
Journal Detail:
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Title: Neurochemical research Volume: - ISSN: 1573-6903 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-24 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7613461 Medline TA: Neurochem Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Immunology, Institute of NeuroImmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA, vpichili@fiu.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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