title: Disrupted anabolic and catabolic processes may contribute to alcohol-accentuated SAIDS-associated wasting.
abstract: BACKGROUND
  Alcohol abuse is a comorbid factor in many human immunodeficiency virus (HIV)-infected patients. Previously, we demonstrated that chronic binge alcohol accentuates loss of body mass at terminal stage of simian immunodeficiency virus (SIV) infection. The purpose of this study was to investigate changes in pathways that may contribute to muscle wasting in chronic binge alcohol-fed SIV-infected macaques.
  
  
  METHODS
  The impact of chronic binge alcohol during SIV infection on insulin signaling and the ubiquitin (Ub)-proteasome system-regulators of protein synthesis and degradation-was examined in SIV-infected macaques.
  
  
  RESULTS
  SIV infection induced an inflammatory and pro-oxidative milieu in skeletal muscle, which was associated with decreased insulin-stimulated phosphatidylinositol 3-kinase (PI-3k) activity and upregulated gene expression of mTOR and atrogin-1, and protein expression of Ub-proteasome system 19S base. Chronic binge alcohol accentuated the skeletal muscle pro-oxidative milieu and 19S base expression. Additionally, chronic binge alcohol increased skeletal muscle protein expression of protein-tyrosine phosphatase 1B (a negative regulator of insulin signaling) and 19S proteasome regulator non-ATPase (Rpn) 6 subunit and Rpn12, and suppressed PI-3K activity. Animals that were alcohol-fed and SIV-infected for >15 months had increased Ub-proteasome system activity.
  
  
  CONCLUSIONS
  These data suggest negative modulation of insulin signaling coupled with enhanced Ub-proteasome system activity may be central mechanisms underlying chronic binge alcohol-induced accentuation of SIV-associated muscle wasting.
authors.affiliation: Department of Physiology, Louisiana State University, Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: LeCapitaine
authors.forename: Zhong Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Jason P
authors.initials: JP
authors.lastname: Dufour
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Potter
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.forename: Steve
authors.initials: S
authors.lastname: Nelson
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000437:Alcoholism / Q000378:metabolism* / Q000821:virology; D000818:Animals; D015153:Blotting, Western; D007328:Insulin / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000821:virology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000821:virology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D018709:Statistics, Nonparametric; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D007328:Insulin; D009124:Muscle Proteins; D025801:Ubiquitin; D012313:RNA; D058539:Phosphatidylinositol 3-Kinase; D046988:Proteasome Endopeptidase Complex