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Histone modifications and alcohol-induced liver disease: Are altered nutrients the missing link?
Akshata Moghe, Swati Joshi-Barve, Smita Ghare, Leila Gobejishvili, Irina Kirpich, Craig J McClain, Shirish Barve
Akshata Moghe, Swati Joshi-Barve, Smita Ghare, Leila Gobejishvili, Irina Kirpich, Craig J McClain, Shirish Barve, University of Louisville Alcohol Research Center, Louisville, KY 40292, United States
Akshata Moghe, Swati Joshi-Barve, Craig J McClain, Shirish Barve, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States
Swati Joshi-Barve, Smita Ghare, Leila Gobejishvili, Irina Kirpich, Craig J McClain, Shirish Barve, Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY 40292, United States
Craig J McClain, Robley Rex Veterans Affairs Medical Center, Louisville, KY, 40206, United States
Author contributions: All authors contributed to the literature search and the writing of this manuscript.
Supported by The National Institute of Alcohol Abuse and Alcoholism grants AA014371 (to Joshi-Barve S), AA015970 (to McClain CJ), and Office of Dietary Supplements, NIH
Correspondence to: Shirish Barve, PhD, Professor, Department of Medicine, Pharmacology and Toxicology, University of Louisville Medical Center, 505 S. Hancock St., CTR Building, Room #515, Louisville, KY 40292, United States. shirish.barve@louisville.edu
Telephone: +1-502-8525245 Fax: +1-502-8528927
Received: January 17, 2011
Revised: February 12, 2011
Accepted: February 19, 2011
Published online: May 28, 2011
Alcoholism is a major health problem in the United States and worldwide, and alcohol remains the single most significant cause of liver-related diseases and deaths. Alcohol is known to influence nutritional status at many levels including nutrient intake, absorption, utilization, and excretion, and can lead to many nutritional disturbances and deficiencies. Nutrients can dramatically affect gene expression and alcohol-induced nutrient imbalance may be a major contributor to pathogenic gene expression in alcohol-induced liver disease (ALD). There is growing interest regarding epigenetic changes, including histone modifications that regulate gene expression during disease pathogenesis. Notably, modifications of core histones in the nucleosome regulate chromatin structure and DNA methylation, and control gene transcription. This review highlights the role of nutrient disturbances brought about during alcohol metabolism and their impact on epigenetic histone modifications that may contribute to ALD. The review is focused on four critical metabolites, namely, acetate, S-adenosylmethionine, nicotinamide adenine dinucleotide and zinc that are particularly relevant to alcohol metabolism and ALD.
