Binge Alcohol Intake After Hypergravity Stress Sustainably Decreases AMPK and Transcription Factors Necessary for Hepatocyte Survival
| Autor: | Sang Geon Kim, Sang Gil Lee, So Won Chung, Choong Sik Oh, Chan Gyu Lee, Hong Min Wu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Cell Survival Medicine (miscellaneous) FOXO1 Hypergravity AMP-Activated Protein Kinases Toxicology CREB Binge Drinking 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine AMP-activated protein kinase Internal medicine medicine Animals Gene Regulatory Networks Ethanol biology AMPK Mice Inbred C57BL Psychiatry and Mental health 030104 developmental biology medicine.anatomical_structure Endocrinology chemistry 030220 oncology & carcinogenesis Hepatocyte biology.protein Hepatocytes Liver function Transcription Factors |
| Zdroj: | Alcoholism, clinical and experimental research. 41(1) |
| ISSN: | 1530-0277 |
| Popis: | Background 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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