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Chronic Binge Alcohol Administration (CBA) Impairs Skeletal Muscle Mitochondrial Gene Expression in Simian Immunodeficiency Virus (SIV)‐Infected Rhesus Macaques
Author(s) -
Duplanty Anthony A,
Song Kejing,
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.1015.6
Subject(s) - skeletal muscle , simian immunodeficiency virus , mitochondrial biogenesis , biology , endocrinology , medicine , mitochondrion , immunology , virus , microbiology and biotechnology
Previous studies from our laboratory have shown that CBA accentuates muscle wasting at end‐stage SIV infection and this is associated with pro‐oxidative and pro‐inflammatory skeletal muscle milieu as well as dysregulation of myoblast myogenic gene expression and myotube formation. Additionally, muscle of CBA/SIV macaques showed a greater reduction in the number and oxidative capacity (succinate dehydrogenase activity) of type 1 muscle fibers compared to that of sucrose administered SIV‐infected (SUC/SIV) and uninfected controls, Chronic alcohol consumption has been reported to result in mitochondrial DNA damage and impaired biogenesis; and this is considered an important mechanism in the pathogenesis of muscle myopathy. We hypothesized that CBA would impair the expression of genes involved in mitochondrial function in SIV‐infected macaques. Purpose The purpose of this study was to investigate the effects of CBA on expression of selected mitochondrial genes in the skeletal muscle of SIV‐infected rhesus macaques at end‐stage disease. Methods Male rhesus macaques were administered daily CBA (blood alcohol levels ~50 mM) or sucrose (SUC) intragastrically 3 months prior to intravenous SIVmac251 inoculation and continued throughout the study period. Skeletal muscle (gastrocnemius) samples were obtained at necropsy when animals met criteria for euthanasia and total RNA was extracted and mitochondrial gene expression was analyzed by qPCR. Results The relative expression of peroxisome proliferator‐activated receptor gamma, coactivator 1 beta (PGC‐1 beta) and mitofusin‐1 (MFN1) was significantly decreased in the skeletal muscle of CBA/SIV macaques (75% and 39% respectively; P<0.05), without altering the gene expression of MFN2, TFAM, NRF1, NRF2, or PGC‐1 alpha. Conclusion These results indicate that CBA administration decreases expression of genes essential for mitochondrial biogenesis in the skeletal muscle of SIV‐infected rhesus macaques and are in agreement with our previous observations of decreased oxidative capacity of type 1 muscle fibers. We speculate that impaired mitochondrial biogenesis may contribute to the underlying pathophysiology of alcoholic and HIV/AIDS associated myopathy. Developing therapeutic or life style interventions aimed at attenuating mitochondrial dysregulation in persons living with HIV/AIDS with alcohol use disorders should lead to improved muscle function and strength. Support or Funding Information This study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA): T32 Postdoctoral Fellowship (AA07577) and the Comprehensive Alcohol Research Center P60 (AA09803) in the department of Physiology, LSU Heath Science Center, New Orleans, LA.