Linking Dysregulated AMPK Signaling and ER Stress in Ethanol-Induced Liver Injury in Hepatic Alcohol Dehydrogenase Deficient Deer Mice
| Autor: | Samir M. Amer, Mukund P. Srinivasan, Bhupendra S. Kaphalia, Ghulam Ansari, Lata Kaphalia, Kamlesh K. Bhopale, Jie Wan |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Alcoholic liver disease lcsh:QR1-502 AMP-Activated Protein Kinases er stress Biochemistry lcsh:Microbiology Gene Knockout Techniques Mice 0302 clinical medicine ampk signaling deer mice Liver injury biology Chemistry alcohol dehydrogenase Alanine Transaminase CYP2E1 Endoplasmic Reticulum Stress Liver Lipogenesis Blood Alcohol Content 030211 gastroenterology & hepatology hormones hormone substitutes and hormone antagonists Signal Transduction alcoholic liver disease endocrine system medicine.medical_specialty Article 03 medical and health sciences Internal medicine mental disorders medicine Animals AMPK signaling ER stress Liver Diseases Alcoholic Molecular Biology Alcohol dehydrogenase Ethanol urogenital system AMPK Lipid Metabolism medicine.disease Disease Models Animal 030104 developmental biology Endocrinology biology.protein Unfolded protein response Steatosis |
| Zdroj: | Biomolecules; Volume 9; Issue 10; Pages: 560 Biomolecules, Vol 9, Iss 10, p 560 (2019) Biomolecules |
| ISSN: | 2218-273X |
| Popis: | Ethanol (EtOH) metabolism itself can be a predisposing factor for initiation of alcoholic liver disease (ALD). Therefore, a dose dependent study to evaluate liver injury was conducted in hepatic alcohol dehydrogenase (ADH) deficient (ADH−) and ADH normal (ADH+) deer mice fed 1%, 2% or 3.5% EtOH in the liquid diet daily for 2 months. Blood alcohol concentration (BAC), liver injury marker (alanine amino transferase (ALT)), hepatic lipids and cytochrome P450 2E1 (CYP2E1) activity were measured. Liver histology, endoplasmic reticulum (ER) stress, AMP-activated protein kinase (AMPK) signaling and cell death proteins were evaluated. Significantly increased BAC, plasma ALT, hepatic lipids and steatosis were found only in ADH− deer mice fed 3.5% EtOH. Further, a significant ER stress and increased un-spliced X-box binding protein 1 were evident only in ADH− deer mice fed 3.5% EtOH. Both strains fed 3.5% EtOH showed deactivation of AMPK, but increased acetyl Co-A carboxylase 1 and decreased carnitine palmitoyltransferase 1A favoring lipogenesis were found only in ADH− deer mice fed 3.5% EtOH. Therefore, irrespective of CYP2E1 overexpression; EtOH dose and hepatic ADH deficiency contribute to EtOH-induced steatosis and liver injury, suggesting a linkage between ER stress, dysregulated hepatic lipid metabolism and AMPK signaling. |
| Databáze: | OpenAIRE |
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