Zinc and Hepatocyte Nuclear Factor-4a in Alcohol-Induced Intestinal Barrier Dysfunction

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Wei Zhong, Research Scientist (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/

Abstract: Zinc is an essential micronutrient and plays an important role in maintaining intestinal epithelial integrity. Increasing evidence support that zinc homeostasis has significant impact on the intestinal barrier via regulation of epithelial tight junction proteins. Intestinal barrier plays a critical role in the prevention of endotoxin penetration from the intestinal lumen to the blood. Disruption of the intestinal barrier leads to elevation of blood endotoxin level, namely endotoxemia. Endotoxemia may lead to proinflammatory cytokine production and inflammation, thereby being an etiological factor in the pathogenesis of alcoholic liver disease (ALD). Recent studies demonstrated that oxidative stress and zinc deficiency correlate well with alcohol-induced gut leakiness. Alcohol exposure induces oxidative stress which, in turn, releases zinc from proteins. Hepatocyte nuclear factor-4a (HNF-4a) is a zinc finger transcription factor which abundantly distributes in the intestine, particularly the distal intestine. Inactivation of HNF-4a correlates well with alcohol-induced downregulation of tight junction proteins. This review discusses mechanisms involved in alcohol-induced intestinal epithelial barrier disruption with emphasis on the relationship among oxidative stress, zinc deficiency, and HNF-4a inactivation.

Additional Information

Journal of Epithelial Biology & Pharmacology 2012; 5 (Suppl 1-M3):19-27
Language: English
Date: 2012
Zinc deficiency, HNF-4a get permeability, alcoholic liver disease

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