Oxidative Stress in HIV Infection and Alcohol Use: Role of Redox Signals in Modulation of Lipid Rafts and ATP-Binding Cassette Transporters.

Autor: Thangavel S; 1 Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University , Miami, Florida., Mulet CT; 1 Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University , Miami, Florida., Atluri VSR; 1 Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University , Miami, Florida., Agudelo M; 1 Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University , Miami, Florida., Rosenberg R; 2 Department of Health Promotion & Disease Prevention, Robert Stempel School of Public Health, Florida International University , Miami, Florida., Devieux JG; 2 Department of Health Promotion & Disease Prevention, Robert Stempel School of Public Health, Florida International University , Miami, Florida., Nair MPN; 1 Department of Immunology, Institute of NeuroImmune Pharmacology, College of Medicine, Florida International University , Miami, Florida.
Jazyk: angličtina
Zdroj: Antioxidants & redox signaling [Antioxid Redox Signal] 2018 Feb 01; Vol. 28 (4), pp. 324-337.
DOI: 10.1089/ars.2016.6830
Abstrakt: Aims: Human immunodeficiency virus (HIV) infection induces oxidative stress and alcohol use accelerates disease progression, subsequently causing immune dysfunction. However, HIV and alcohol impact on lipid rafts-mediated immune dysfunction remains unknown. In this study, we investigate the modulation by which oxidative stress induces reactive oxygen species (ROS) affecting redox expression, lipid rafts caveiloin-1, ATP-binding cassette (ABC) transporters, and transcriptional sterol regulatory element-binding protein (SREBP) gene and protein modification and how these mechanisms are associated with arachidonic acid (AA) metabolites in HIV positive alcohol users, and how they escalate immune dysfunction.
Results: In both alcohol using HIV-positive human subjects and in vitro studies of alcohol with HIV-1 gp120 protein in peripheral blood mononuclear cells, increased ROS production significantly affected redox expression in glutathione synthetase (GSS), super oxide dismutase (SOD), and glutathione peroxidase (GPx), and subsequently impacted lipid rafts Cav-1, ABC transporters ABCA1, ABCG1, ABCB1, and ABCG4, and SREBP transcription. The increased level of rate-limiting enzyme 3-hydroxy-3-methylglutaryl HMG-CoA reductase (HMGCR), subsequently, inhibited 7-dehydrocholesterol reductase (DHCR-7). Moreover, the expression of cyclooxygenase-2 (COX-2) and lipoxygenase-5 (5-LOX) mRNA and protein modification tentatively increased the levels of prostaglandin E2 synthases (PGE 2 ) in plasma when compared with either HIV or alcohol alone.
Innovation: This article suggests for the first time that the redox inhibition affects lipid rafts, ABC-transporter, and SREBP transcription and modulates AA metabolites, serving as an important intermediate signaling network during immune cell dysfunction in HIV-positive alcohol users.
Conclusion: These findings indicate that HIV infection induces oxidative stress and redox inhibition, affecting lipid rafts and ABC transports, subsequently upregulating AA metabolites and leading to immune toxicity, and further exacerbation with alcohol use. Antioxid. Redox Signal. 28, 324-337.
Databáze: MEDLINE
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