Chronic binge alcohol-induced dysregulation of mitochondrial-related genes in skeletal muscle of simian immunodeficiency virus-infected rhesus macaques at end-stage disease

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dc.contributor.authorDuplanty, Anthony A.
dc.contributor.authorSimon, Liz
dc.contributor.authorMolina, Patricia E.
dc.creator.orcidhttps://orcid.org/0000-0002-3506-048X
dc.date.accessioned2019-03-13T18:48:11Z
dc.date.available2019-03-13T18:48:11Z
dc.date.issued2017-01
dc.description.abstractAims: Alcohol use disorders are more prevalent in HIV patients than the general population. Both chronic alcohol consumption and HIV infection have been linked to mitochondrial dysregulation; and this is considered an important mechanism in the pathogenesis of muscle myopathy. This study investigated if chronic binge alcohol (CBA) administration impairs the expression of genes involved in mitochondrial homeostasis in SIV-infected macaques. Methods: Male rhesus macaques were administered daily CBA (to achieve peak blood alcohol concentrations of 50–60 mM within 2 h after start of infusion) or sucrose (SUC) intragastrically 3 months prior to intravenous SIVmac251 inoculation and continued until macaques met criteria for end-stage disease. Skeletal muscle (SKM) samples were obtained at necropsy. Muscle samples were obtained from a cohort of healthy uninfected macaque controls and used for comparison of analyzed variables. Total RNA was extracted and gene expression was analyzed by quantitative polymerase chain reaction. Results: The relative expression of peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1β) was significantly decreased in the SKM of CBA/simian immunodeficiency virus (SIV) macaques compared to uninfected controls (P < 0.05). SIV infection resulted in a significant upregulation (P < 0.05) of mitophagy-related gene expression, which was prevented by CBA. CBA suppressed expression of anti-apoptotic genes and increased expression of pro-apoptotic genes (P < 0.05). Conclusions: These findings suggest that SIV infection disrupts mitochondrial homeostasis and when combined with CBA, results in differential expression of genes involved in apoptotic signaling. We speculate that impaired mitochondrial homeostasis may contribute to the underlying pathophysiology of alcoholic and HIV/AIDS associated myopathy. Short summary: This study investigated if CBA administration dysregulates gene expression associated with mitochondrial homeostasis in the SKM of SIV-infected macaques. The results suggest that SIV infection disrupts mitochondrial homeostasis and when combined with CBA, results in differential expression of genes involved in apoptotic signaling.en_US
dc.identifier.citationThis is an abstract of an article that is available at https://doi.org/10.1093/alcalc/agw107. Recommended citation: Duplanty, A. A., Simon, L., & Molina, P. E. (2017). Chronic binge alcohol-induced dysregulation of mitochondrial-related genes in skeletal muscle of simian immunodeficiency virus-infected rhesus macaques at end-stage disease. Alcohol and Alcoholism, 52(3), 298–304. https://doi.org/10.1093/alcalc/agw107. This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.identifier.urihttps://hdl.handle.net/11274/11093
dc.identifier.urihttps://doi.org/10.1093/alcalc/agw107
dc.language.isoen_USen_US
dc.publisherOxford University Pressen_US
dc.subjectEthanolen_US
dc.subjectPolymerase chain reactionen_US
dc.subjectHIVen_US
dc.subjectSignal transductionen_US
dc.subjectGene expressionen_US
dc.subjectMitochondriaen_US
dc.subjectHomeostasisen_US
dc.subjectAlcohol drinkingen_US
dc.subjectAutopsyen_US
dc.subjectGenesen_US
dc.subjectImmunologicen_US
dc.subjectImmunologic deficiency syndromesen_US
dc.subjectMacacaen_US
dc.subjectMacaca mulattaen_US
dc.subjectSkeletal musclesen_US
dc.subjectMyopathyen_US
dc.subjectSimian immunodeficiency virusen_US
dc.subjectSucroseen_US
dc.subjectUp-regulation (physiology)en_US
dc.subjectInfectionen_US
dc.subjectVirusesen_US
dc.subjectPeroxisomeen_US
dc.subjectPeroxisome proliferator-activated receptorsen_US
dc.subjectRNAen_US
dc.subjectHIV infectionsen_US
dc.subjectBlood alcohol concentrationen_US
dc.subjectAlcohol use disorderen_US
dc.titleChronic binge alcohol-induced dysregulation of mitochondrial-related genes in skeletal muscle of simian immunodeficiency virus-infected rhesus macaques at end-stage diseaseen_US
dc.typeAbstracten_US

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