title: Binge Alcohol Intake After Hypergravity Stress Sustainably Decreases AMPK and Transcription Factors Necessary for Hepatocyte Survival.
abstract: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival.
  
  
  
  The mice were orally administered a single dose of EtOH (5 g/kg body weight, 20% EtOH) immediately after a load to +9 Gz hypergravity for 1 hour using a small animal centrifuge and sacrificed 24 hours after treatment. For the multiple-dose model, 3 consecutive daily treatments were carried out. Immunoblottings were carried out on liver homogenates.
  
  
  
  Binge alcohol intake in mice immediately after a 1-hour exposure to a +9 Gz hypergravity load repressed hepatic Akt and PARP-1 levels at 24 hours posttreatment. Moreover, it sustainably diminished the level of AMPKα, a key regulator of energy metabolism, as compared to each individual treatment. Similarly, the combination of alcohol and hypergravity suppressed the levels of STAT3, FOXO1/3, C/EBPβ, and CREB, transcription factors necessary for cell survival. Similar changes were not detected after 3 consecutive daily combinatorial treatments, indicating that repetitive training with hypergravity loads provides hepatoprotective effects in a binge alcohol model.
  
  
  
  These results show that binge alcohol exposure in mice immediately following a +9 Gz hypergravity stress persistently decreased AMPKα and other key molecules required for hepatocyte survival, and these changes may be reversed by repetitive hypergravity loads.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Sang Gil
authors.initials: SG
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Wu
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Chan Gyu
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Aerospace Medical Center, ROKAF, Cheong-ju, Korea.
authors.forename: Choong Sik
authors.initials: CS
authors.lastname: Oh
authors.affiliation: Aerospace Medical Center, ROKAF, Cheong-ju, Korea.
authors.forename: So Won
authors.initials: SW
authors.lastname: Chung
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D063425:Binge Drinking / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage; D053263:Gene Regulatory Networks / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D018471:Hypergravity / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D000431:Ethanol; D055372:AMP-Activated Protein Kinases
keywords: AMP-Activated Protein Kinase; Adaptation; Alcohol Intake; Apoptosis; Gravitational Force