Premium
Chronic Binge Alcohol (CBA) Administration decreases miR‐206 in simian immunodeficiency virus (SIV)‐infected Macaques
Author(s) -
Simon Liz,
Molina Patricia E
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1244.6
Subject(s) - simian immunodeficiency virus , biology , wasting , lentivirus , viral load , myogenesis , immunology , population , virology , virus , medicine , endocrinology , myocyte , viral disease , environmental health
Decreased skeletal muscle (SKM) mass and function remains a strong and consistent predictor of mortality among persons living with HIV/AIDS (PLWHA) and occurs at an earlier age among PLWHA compared to the general population. SKM dysfunction is also prevalent in individuals with alcohol use disorders (AUDs). Previously we showed that CBA accentuates SKM wasting in simian immunodeficiency virus (SIV) infected rhesus macaques and this is associated with enhanced myoinflammation, oxidative stress, ubiquitin proteasome proteolytic pathways, and decreased regenerative capacity of SKM progenitor cells. This study tested the hypothesis that CBA‐induced alterations in SKM microRNA (myomiR) expression may contributing to impaired SKM regeneration in SIV‐infected macaques. Daily CBA (blood alcohol levels ~50 mM) or sucrose (SUC) administration was initiated 3 months prior to intrarectal SIV mac251 inoculation and continued throughout the study period. Antiretroviral therapy (ART) or placebo was initiated 2.5 months after SIV infection and continued through the study period. Four treatment groups (SUC/SIV±ART and CBA/SIV±ART) were studied at endpoint (11 months post SIV inoculation). Primary myoblasts isolated from SKM samples from CBA/SIV/ART+/− showed decreased myotube formation, myonuclei fusion index, and myogenic gene expression compared to those derived from SUC/SIV macaques. This was associated with decreased SKM miR‐206 expression. Transfection of naïve macaque myoblasts with a miR‐206 inhibitor resulted in a significant decrease in myogenic enhancer factor 2C (MEF2C), and decreased differentiation of myoblasts, suggesting a critical role of miR‐206 in myogenesis in macaque myoblasts. Circulating plasma levels of miR‐206 were significantly decreased in CBA/SIV/ART+/− macaques, reflecting a similar pattern to that seen in SKM. These results suggest altered SKM myomiR expression as a likely mechanism for decreased regenerative capacity in SKM of CBA/SIV macaques, irrespective of ART. The parallel changes in SKM and circulating levels of miR‐206 suggest the possible use of plasma miR‐206 as an indicator of impaired regenerative capacity in SKM of PLWHA and is currently under investigation. Support or Funding Information The work was supported by National Institutes of Health (NIH) grants: P60 AA09803