Hyperhomocysteinemia, endoplasmic reticulum stress, and alcoholic liver injury

Deficiencies in vitamins or other factors(B6,B12,folic acid,betaine)and genetic disorders for the metabolism of thenon-protein amino acid-homocysteine(Hcy)lead tohyperhomocysteinemia(HHcy).HHcy is an integralcomponent of several disorders including cardiovasculardisease,neurodegeneration,diabetes and alcoholic liverdisease.HHcy unleashes mediators of inflammation such asNFκB,IL-1β,IL-6,and IL-8,increases production ofintracellular superoxide anion causing oxidative stress andreducing intracellular level of nitric oxide(NO),and inducesendoplasrnic reticulum(ER)stress which can explain manyprocesses of Hcy-promoted cell injury such as apoptosis,fat accumulation,and inflammation.Animal models haveplayed an important role in determining the biological effectsof HHcy.ER stress may also be involved in other liver diseasessuch as α1-antitrypsin(α1-AT)deficiency and hepatitis Cand/or B virus infection.Future research should evaluatethe possible potentiative effects of alcohol and hepatic virusinfection on ER stress-induced liver injury,study potentiallybeneficial effects of lowering Hcy and preventing ER stressin alcoholic humans,and examine polymorphisrn of Hcymetabolizing enzymes as potential risk-factors for thedevelopment of HHcy and liver disease.