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Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques
BACKGROUND: There are more than 1 million persons living with HIV/AIDS (PLWHA) in the United States and approximately 40 % of them have a history of alcohol use disorders (AUD). Chronic heavy alcohol consumption and HIV/AIDS both result in reduced lean body mass and muscle dysfunction, increasing th...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690320/ https://www.ncbi.nlm.nih.gov/pubmed/26699868 http://dx.doi.org/10.1186/s12864-015-2329-z |
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author | Simon, Liz Hollenbach, Andrew D. Zabaleta, Jovanny Molina, Patricia E. |
author_facet | Simon, Liz Hollenbach, Andrew D. Zabaleta, Jovanny Molina, Patricia E. |
author_sort | Simon, Liz |
collection | PubMed |
description | BACKGROUND: There are more than 1 million persons living with HIV/AIDS (PLWHA) in the United States and approximately 40 % of them have a history of alcohol use disorders (AUD). Chronic heavy alcohol consumption and HIV/AIDS both result in reduced lean body mass and muscle dysfunction, increasing the incidence of comorbid conditions. Previous studies from our laboratory using rhesus macaques infected with Simian Immunodeficiency Virus (SIV) demonstrated that chronic binge alcohol (CBA) administration in the absence of antiretroviral therapy exacerbates skeletal muscle (SKM) wasting at end-stage SIV disease. The aim of this study was to characterize how CBA alters global gene regulatory networks that lead to SKM wasting at end-stage disease. Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. High-output array analysis was used to determine CBA-dependent changes in mRNA expression, miRNA expression, and promoter methylation status of SKM at end-stage disease (~10 months post-SIV) from healthy control (control), sucrose-administered, SIV-infected (SUC/SIV), and CBA-administered/SIV-infected (CBA/SIV) macaques. RESULTS: In addition to previously reported effects on the extracellular matrix and the promotion of a pro-inflammatory environment, we found that CBA adversely affects gene regulatory networks that involve “universal” cellular functions, protein homeostasis, calcium and ion homeostasis, neuronal growth and signaling, and satellite cell growth and survival. CONCLUSIONS: The results from this study provide an overview of the impact of CBA on gene regulatory networks involved in biological functions, including transcriptional and epigenetic processes, illustrating the genetic and molecular mechanisms associated with CBA-dependent SKM wasting at end-stage SIV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2329-z) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4690320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-46903202015-12-25 Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques Simon, Liz Hollenbach, Andrew D. Zabaleta, Jovanny Molina, Patricia E. BMC Genomics Research Article BACKGROUND: There are more than 1 million persons living with HIV/AIDS (PLWHA) in the United States and approximately 40 % of them have a history of alcohol use disorders (AUD). Chronic heavy alcohol consumption and HIV/AIDS both result in reduced lean body mass and muscle dysfunction, increasing the incidence of comorbid conditions. Previous studies from our laboratory using rhesus macaques infected with Simian Immunodeficiency Virus (SIV) demonstrated that chronic binge alcohol (CBA) administration in the absence of antiretroviral therapy exacerbates skeletal muscle (SKM) wasting at end-stage SIV disease. The aim of this study was to characterize how CBA alters global gene regulatory networks that lead to SKM wasting at end-stage disease. Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. High-output array analysis was used to determine CBA-dependent changes in mRNA expression, miRNA expression, and promoter methylation status of SKM at end-stage disease (~10 months post-SIV) from healthy control (control), sucrose-administered, SIV-infected (SUC/SIV), and CBA-administered/SIV-infected (CBA/SIV) macaques. RESULTS: In addition to previously reported effects on the extracellular matrix and the promotion of a pro-inflammatory environment, we found that CBA adversely affects gene regulatory networks that involve “universal” cellular functions, protein homeostasis, calcium and ion homeostasis, neuronal growth and signaling, and satellite cell growth and survival. CONCLUSIONS: The results from this study provide an overview of the impact of CBA on gene regulatory networks involved in biological functions, including transcriptional and epigenetic processes, illustrating the genetic and molecular mechanisms associated with CBA-dependent SKM wasting at end-stage SIV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2329-z) contains supplementary material, which is available to authorized users. BioMed Central 2015-12-23 /pmc/articles/PMC4690320/ /pubmed/26699868 http://dx.doi.org/10.1186/s12864-015-2329-z Text en © Simon et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Simon, Liz Hollenbach, Andrew D. Zabaleta, Jovanny Molina, Patricia E. Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title | Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title_full | Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title_fullStr | Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title_full_unstemmed | Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title_short | Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
title_sort | chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690320/ https://www.ncbi.nlm.nih.gov/pubmed/26699868 http://dx.doi.org/10.1186/s12864-015-2329-z |
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