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Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury

Cheng Ji1, Neil Kaplowitz

  • 1Faculty of Medicine, Gastroenterology/Liver Division, Keck School of Medicine, University of Southern California, HMR-101, 2011 Zonal Avenue, Los Angeles, CA 90033, USA. chengji@usc.edu

World Journal of Gastroenterology
|June 10, 2004
PubMed

Insights

Hyperhomocysteinemia (HHcy), caused by vitamin deficiencies or genetic factors, contributes to cardiovascular disease, neurodegeneration, and liver disease. HHcy induces inflammation and endoplasmic reticulum stress, damaging cells.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pathology

Background:

  • Hyperhomocysteinemia (HHcy) results from impaired homocysteine metabolism due to vitamin deficiencies (B6, B12, folic acid, betaine) or genetic factors.
  • HHcy is implicated in various diseases, including cardiovascular disease, neurodegeneration, diabetes, and alcoholic liver disease.
  • HHcy triggers inflammatory mediators (NF-kappaB, IL-1beta, IL-6, IL-8), oxidative stress, and endoplasmic reticulum (ER) stress, contributing to cell injury.

Purpose of the Study:

  • To elucidate the mechanisms by which hyperhomocysteinemia (HHcy) promotes cell injury.
  • To explore the role of endoplasmic reticulum (ER) stress in HHcy-induced pathologies, particularly in liver disease.
  • To highlight the importance of animal models in understanding HHcy's biological effects.

Main Methods:

  • Review of existing literature on hyperhomocysteinemia (HHcy) and its associated conditions.
  • Analysis of the molecular pathways involved in HHcy, including inflammation, oxidative stress, and ER stress.
  • Consideration of findings from animal models investigating HHcy's effects.

Main Results:

  • HHcy activates inflammatory pathways and increases oxidative stress, reducing nitric oxide (NO) levels.
  • HHcy induces endoplasmic reticulum (ER) stress, leading to apoptosis, fat accumulation, and inflammation.
  • ER stress is also implicated in other liver conditions like alpha(1)-antitrypsin deficiency and viral hepatitis.

Conclusions:

  • HHcy-induced ER stress is a key mechanism underlying cell injury in various diseases.
  • Further research is needed to investigate the combined effects of alcohol/viral infections and ER stress on liver injury.
  • Exploring Hcy-metabolizing enzyme polymorphisms may identify risks for HHcy and liver disease.

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