Role of HIF-1α in Alcohol-Mediated Multiple Organ Dysfunction

Biomolecules. 2018 Dec 10;8(4):170. doi: 10.3390/biom8040170.

Abstract

Excess alcohol consumption is a global crisis contributing to over 3 million alcohol-related deaths per year worldwide and economic costs exceeding $200 billion dollars, which include productivity losses, healthcare, and other effects (e.g., property damages). Both clinical and experimental models have shown that excessive alcohol consumption results in multiple organ injury. Although alcohol metabolism occurs primarily in the liver, alcohol exposure can lead to pathophysiological conditions in multiple organs and tissues, including the brain, lungs, adipose, liver, and intestines. Understanding the mechanisms by which alcohol-mediated organ dysfunction occurs could help to identify new therapeutic approaches to mitigate the detrimental effects of alcohol misuse. Hypoxia-inducible factor (HIF)-1 is a transcription factor comprised of HIF-1α and HIF-1β subunits that play a critical role in alcohol-mediated organ dysfunction. This review provides a comprehensive analysis of recent studies examining the relationship between HIF-1α and alcohol consumption as it relates to multiple organ injury and potential therapies to mitigate alcohol's effects.

Keywords: HIF-1α; alcohol; ethanol.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Alcohol Drinking / adverse effects
  • Alcohol Drinking / genetics
  • Aryl Hydrocarbon Receptor Nuclear Translocator / genetics*
  • Ethanol / adverse effects*
  • Ethanol / toxicity
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics*
  • Liver / drug effects
  • Liver / pathology
  • Multiple Organ Failure / chemically induced
  • Multiple Organ Failure / genetics*
  • Multiple Organ Failure / pathology

Substances

  • ARNT protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Ethanol