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Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury 预览 被引量:8

Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury
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摘要 Deficiencies in vitamins or other factors (B6, B12, folic acid, betaine) and genetic disorders for the metabolism of the non-protein amino acid-homocysteine (Hcy) lead to hyperhomocysteinemia (HHcy). HHcy is an integral component of several disorders including cardiovascular disease, neurodegeneration, diabetes and alcoholic liver disease. HHcy unleashes mediators of inflammation such as NFkB, IL-1β, IL-6, and IL-8, increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide (NO), and induces endoplasmic reticulum (ER) stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation, and inflammation. Animal models have played an important role in determining the biological effects of HHcy. ER stress may also be involved in other liver diseases such as a1-antitrypsin (a1-AT) deficiency and hepatitis C and/or B virus infection. Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury, study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans, and examine polymorphism of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease. Deficiencies in vitamins or other factors(B6,B12,folic acid, betaine)and genetic disorders for the metabolism of the non-protein amino acid-homocysteine(Hcy)lead to hyperhomocysteinemia(HHcy).HHcy is an integral component of several disorders including cardiovascular disease,neurodegeneration,diabetes and alcoholic liver disease.HHcy unleashes mediators of inflammation such as NFκB,IL-1β,IL-6,and IL-8,increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide(NO),and induces endoplasrnic reticulum(ER)stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation,and inflammation.Animal models have played an important role in determining the biological effects of HHcy.ER stress may also be involved in other liver diseases such as α_1-antitrypsin(α_1-AT)deficiency and hepatitis C and/or B virus infection.Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury,study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans,and examine polymorphisrn of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.
作者 ChengJi NeilKaplowitz Cheng Ji Neil Kaplowitz,Gastroenterology/Liver Division,Keck School of Medicine,University of Southern California,Los Angeles,CA 90033,USA
出处 《世界胃肠病学杂志:英文版(电子版)》 SCIE CAS CSCD 2004年第12期1699-1708,共10页 World Journal of Gastroenterology
基金 Supported by the U.S.National Institute of Alcohol Abuse and Alcoholism,R01 AA014428 and by the Robert E.and May R.Wright Foundation,No.263
关键词 内质网 酒精肝 肝损害 HHCY 心血管疾病 糖尿病 Animals Endoplasmic Reticulum Humans Hyperhomocysteinemia Liver Diseases, Alcoholic Oxidative Stress
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