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 ma...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.展开更多
As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and path...As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases(CVDs),such as ischemic heart failure(HF),myocardial hypertrophy,myocardial infarction(MI),and cardiomyogenesis.Regulation is achieved by modulating the expression of m^6 A enzymes and their downstream cardiac genes.In addition,this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs.However,the exact molecular mechanism of m^6 A epigenetic regulation has not been fully elucidated.In this review,we outline recent advances and discuss potential therapeutic strategies for managing m^6 A in relation to several common CVD-related metabolic disorders and external environmental factors.Note that an appropriate understanding of the biological function of m^6 A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms.Finally,it can provide new insights for the development of novel therapeutic agents for use in clinical practice.展开更多
基金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
文摘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.
基金Project supported by the Grants-in-Aid from the Graduate Research and Innovation Projects of Jiangsu Province(No.KYCX18_1461),China。
文摘As the most prevalent and abundant transcriptional modification in the eukaryotic genome,the continuous and dynamic regulation of N^6-methyladenosine(m^6 A)has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases(CVDs),such as ischemic heart failure(HF),myocardial hypertrophy,myocardial infarction(MI),and cardiomyogenesis.Regulation is achieved by modulating the expression of m^6 A enzymes and their downstream cardiac genes.In addition,this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs.However,the exact molecular mechanism of m^6 A epigenetic regulation has not been fully elucidated.In this review,we outline recent advances and discuss potential therapeutic strategies for managing m^6 A in relation to several common CVD-related metabolic disorders and external environmental factors.Note that an appropriate understanding of the biological function of m^6 A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms.Finally,it can provide new insights for the development of novel therapeutic agents for use in clinical practice.
