Oxidative Stress in HIV Infection and Alcohol Use: Role of Redox Signals in Modulation of Lipid Rafts and ATP-Binding Cassette Transporters.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
HIV infection | increase | oxidative stress | - | - | induces | #1 |
alcohol use | increase | disease progression | HIV positive alcohol users | - | accelerates | #2 |
alcohol with HIV-1 gp120 protein | increase | ROS production | peripheral blood mononuclear cells | - | increased | #3 |
increased ROS production | increase | redox expression in glutathione synthetase (GSS), super oxide dismutase (SOD), and glutathione peroxidase (GPx) | alcohol using HIV-positive human subjects and in vitro studies | - | significantly affected | #4 |
increased ROS production | increase | lipid rafts Cav-1, ABC transporters ABCA1, ABCG1, ABCB1, and ABCG4, and SREBP transcription | alcohol using HIV-positive human subjects and in vitro studies | - | impacted | #5 |
increased level of rate-limiting enzyme 3-hydroxy-3-methylglutaryl HMG-CoA reductase (HMGCR) | decrease | 7-dehydrocholesterol reductase (DHCR-7) | - | - | inhibited | #6 |
expression of cyclooxygenase-2 (COX-2) and lipoxygenase-5 (5-LOX) mRNA and protein modification | increase | levels of prostaglandin E2 synthases (PGE | - | - | tentatively increased | #7 |
redox inhibition | increase | lipid rafts, ABC-transporter, and SREBP transcription | HIV-positive alcohol users | - | affects | #8 |
redox inhibition | increase | AA metabolites | HIV-positive alcohol users | - | modulates | #9 |
HIV infection | increase | oxidative stress and redox inhibition | - | - | induces | #10 |
oxidative stress and redox inhibition | increase | lipid rafts and ABC transports | - | - | affecting | #11 |
affecting lipid rafts and ABC transports | increase | AA metabolites | - | - | subsequently upregulating | #12 |
upregulating AA metabolites | increase | immune toxicity | - | - | leading to | #13 |
alcohol use | increase | immune toxicity | - | - | further exacerbation | #14 |
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 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.