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HIV-1 viral envelope glycoprotein gp120 produces oxidative stress and regulates the functional expression of multidrug resistance protein-1 (Mrp1) in glial cells.
J Neurochem. 2008 Aug; 106(3):1298-313.JN

Abstract

Brain human immunodeficiency virus type-1 (HIV-1) infection is associated with oxidative stress, which may lead to HIV-1 encephalitis, a chronic neurodegenerative condition. In vitro, oxidative stress can be induced in glial cells by exposure to HIV-1 envelope protein glycoprotein (gp120). Multidrug resistance proteins (Mrps) are known to efflux endogenous substrates (i.e. GSH and GSSG) involved in cellular defense against oxidative stress. Altered GSH/GSSG export may contribute to oxidative damage during HIV-1 encephalitis. At present, it is unknown if gp120 exposure can alter the functional expression of Mrp isoforms. Heat-shock protein 70, inducible nitric oxide synthase, intracellular GSSG, 2',7'-dichlorofluorescein fluorescence, and extracellular nitrite were increased in primary cultures of rat astrocytes triggered with gp120, suggesting an oxidative stress response. RT-PCR and immunoblot analysis demonstrated increased Mrp1 mRNA (2.3-fold) and protein (2.2-fold), respectively, in gp120 treated astrocytes while Mrp4 mRNA or protein expression was not changed. Cellular retention of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, an established Mrp substrate, was reduced (twofold) in gp120-treated astrocytes, suggesting increased Mrp-mediated transport. In addition, GSH and GSSG export were enhanced in gp120-triggered cells. These data suggest that gp120 can up-regulate Mrp1, but not Mrp4, functional expression in cultured astrocytes. Our observation of increased GSH/GSSG efflux in response to gp120 treatment implies that Mrp isoforms may be involved in regulating the oxidative stress response in glial cells.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18485102

Citation

Ronaldson, Patrick T., and Reina Bendayan. "HIV-1 Viral Envelope Glycoprotein Gp120 Produces Oxidative Stress and Regulates the Functional Expression of Multidrug Resistance Protein-1 (Mrp1) in Glial Cells." Journal of Neurochemistry, vol. 106, no. 3, 2008, pp. 1298-313.
Ronaldson PT, Bendayan R. HIV-1 viral envelope glycoprotein gp120 produces oxidative stress and regulates the functional expression of multidrug resistance protein-1 (Mrp1) in glial cells. J Neurochem. 2008;106(3):1298-313.
Ronaldson, P. T., & Bendayan, R. (2008). HIV-1 viral envelope glycoprotein gp120 produces oxidative stress and regulates the functional expression of multidrug resistance protein-1 (Mrp1) in glial cells. Journal of Neurochemistry, 106(3), 1298-313. https://doi.org/10.1111/j.1471-4159.2008.05479.x
Ronaldson PT, Bendayan R. HIV-1 Viral Envelope Glycoprotein Gp120 Produces Oxidative Stress and Regulates the Functional Expression of Multidrug Resistance Protein-1 (Mrp1) in Glial Cells. J Neurochem. 2008;106(3):1298-313. PubMed PMID: 18485102.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 viral envelope glycoprotein gp120 produces oxidative stress and regulates the functional expression of multidrug resistance protein-1 (Mrp1) in glial cells. AU - Ronaldson,Patrick T, AU - Bendayan,Reina, Y1 - 2008/05/12/ PY - 2008/5/20/pubmed PY - 2008/9/16/medline PY - 2008/5/20/entrez SP - 1298 EP - 313 JF - Journal of neurochemistry JO - J Neurochem VL - 106 IS - 3 N2 - Brain human immunodeficiency virus type-1 (HIV-1) infection is associated with oxidative stress, which may lead to HIV-1 encephalitis, a chronic neurodegenerative condition. In vitro, oxidative stress can be induced in glial cells by exposure to HIV-1 envelope protein glycoprotein (gp120). Multidrug resistance proteins (Mrps) are known to efflux endogenous substrates (i.e. GSH and GSSG) involved in cellular defense against oxidative stress. Altered GSH/GSSG export may contribute to oxidative damage during HIV-1 encephalitis. At present, it is unknown if gp120 exposure can alter the functional expression of Mrp isoforms. Heat-shock protein 70, inducible nitric oxide synthase, intracellular GSSG, 2',7'-dichlorofluorescein fluorescence, and extracellular nitrite were increased in primary cultures of rat astrocytes triggered with gp120, suggesting an oxidative stress response. RT-PCR and immunoblot analysis demonstrated increased Mrp1 mRNA (2.3-fold) and protein (2.2-fold), respectively, in gp120 treated astrocytes while Mrp4 mRNA or protein expression was not changed. Cellular retention of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, an established Mrp substrate, was reduced (twofold) in gp120-treated astrocytes, suggesting increased Mrp-mediated transport. In addition, GSH and GSSG export were enhanced in gp120-triggered cells. These data suggest that gp120 can up-regulate Mrp1, but not Mrp4, functional expression in cultured astrocytes. Our observation of increased GSH/GSSG efflux in response to gp120 treatment implies that Mrp isoforms may be involved in regulating the oxidative stress response in glial cells. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/18485102/HIV_1_viral_envelope_glycoprotein_gp120_produces_oxidative_stress_and_regulates_the_functional_expression_of_multidrug_resistance_protein_1__Mrp1__in_glial_cells_ L2 - https://doi.org/10.1111/j.1471-4159.2008.05479.x DB - PRIME DP - Unbound Medicine ER -