Premium
Chronic Binge Alcohol Upregulates Expression of Genes Related to Apoptosis in Skeletal Muscle of Simian Immunodeficiency Virus‐Infected Rhesus Macaques at End‐Stage Disease
Author(s) -
Duplanty Anthony A,
Simon Liz,
Molina Patricia E
Publication year - 2017
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.31.1_supplement.1081.7
Subject(s) - simian immunodeficiency virus , biology , skeletal muscle , immunology , wasting , medicine , endocrinology , virus
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. Previous studies from our laboratory have demonstrated that chronic binge alcohol (CBA) administration accentuated loss of skeletal muscle (SKM) mass and promoted a dysfunctional skeletal muscle phenotype which was associated with accelerated progression to end‐stage disease, compared with isocaloric sucrose simian immunodeficiency virus (SIV)‐infected (SUC/SIV) macaques. The mechanisms preceding and leading to accentuated SAIDS wasting in CBA/SIV macaques include localized SKM inflammation, increased proteasomal activity, depletion of SKM antioxidant capacity and increased expression of pro‐fibrotic genes. Moreover, CBA/SIV resulted in decreased expression of peroxisome proliferator‐activated receptor‐γ coactivator (PGC)‐1β, a master regulator of mitochondrial homeostasis. Purpose The aim of this study was to investigate the CBA‐associated alterations in expression of selected mitochondrial genes related to mitophagy and apoptosis 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 until animals reached end‐stage criteria. SKM (gastrocnemius) samples were excised at necropsy and total RNA was extracted and mitochondrial gene expression was analyzed by qPCR. SKM tissues excised from a group of uninfected non‐CBA treated animals was used as reference controls. Results SIV‐infection resulted in a significant upregulation (P<0.05) of mitophagy‐related gene expression (DRP1, TFEB, PINK1), which was prevented by CBA. CBA suppressed expression of anti‐apoptotic genes (Beclin‐1 and BCL2) and increased expression of pro‐apoptotic genes (BAX and BAK) (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. 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.