Linking dysregulated ampk signaling and er stress in ethanol-induced liver injury in hepatic alcohol dehydrogenase deficient deer mice

Bhupendra S. Kaphalia, Mukund P. Srinivasan, Kamlesh K. Bhopale, Samir M. Amer, Jie Wan, Lata Kaphalia, Ghulam S. Ansari

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number560
JournalBiomolecules
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Linking dysregulated ampk signaling and er stress in ethanol-induced liver injury in hepatic alcohol dehydrogenase deficient deer mice'. Together they form a unique fingerprint.

Cite this