scholarly journals Role of TNF-? in ethanol-induced hyperhomocysteinemia and murine alcoholic liver injury

Hepatology ◽  
2004 ◽  
Vol 40 (2) ◽  
pp. 442-451 ◽  
Author(s):  
Cheng Ji ◽  
Qinggao Deng ◽  
Neil Kaplowitz
Keyword(s):  
Liver Injury ◽  
Alcoholic Liver Injury

scholarly journals Contribution of glutaredoxin-1 to Fas s-glutathionylation in ethanol-induced liver injury

2020 ◽  
Author(s):  
Xiaomin Sun ◽  
Qin Deng ◽  
Yunfei Zhang ◽  
Jingyu Chen ◽  
chunbao guo
Keyword(s):  
Liver Injury ◽  
Alcohol Exposure ◽  
Nuclear Factor Κb ◽  
Signaling Cascades ◽  
Alcoholic Liver Injury ◽  
Genetic Ablation ◽  
Induced Apoptosis ◽  
The Impact ◽  
Deficient Mice

Abstract Background The reversible glutathionylation modification (PSSG) of Fas augments apoptosis, which can be reversed by the cytosolic deglutathionylation enzyme glutaredoxin-1 (Grx1), but its roles in alcoholic liver injury remain unknown. Therefore, the objective of this study was to investigate the impact of genetic ablation of Grx1 on Fas-SSG in regulating ethanol-induced injury. Methods The role of Grx1 in alcoholic liver injury was investigated in Grx1 knockout mice. Alcoholic liver injury was achieved by feeding mice with a liquid diet containing 5% ethanol for 2 weeks. Results We demonstrated that ethanol-fed mice had increased Grx1 activity and oxidative damage in the liver. On the other hand, Grx1-deficient mice had more serious liver damage when exposed to ethanol compared to that of wild-type mice, accompanied by increased alanine aminotransferase and aspartate aminotransferase levels, Fas-SSG, cleaved caspase-3 and hepatocyte apoptosis. Grx1 ablation resulted in the suppression of ethanol-induced nuclear factor-κB (NF-κB) signaling, its downstream signal, and Akt signaling cascades, which are required for protection against Fas-mediated apoptosis. Accordingly, blocking NK-κB prevented Fas-induced apoptosis in WT mice but not Grx1-/- mice. Furthermore, the number of Kupffer cells and related proinflammatory cytokines, including Akt, were lower in Grx1-/- livers than those of the controls. Conclusions Grx1 is essential for adaptation to alcohol exposure-induced oxidative injury by modulating Fas-SSG and Fas-induced apoptosis.

scholarly journals The functional role of micro RNA s in alcoholic liver injury

2014 ◽  
Vol 18 (2) ◽  
pp. 197-207 ◽  
Author(s):  
Kelly McDaniel ◽  
Leonardo Herrera ◽  
Tianhao Zhou ◽  
Heather Francis ◽  
Yuyan Han ◽  
...  
Keyword(s):  
Liver Injury ◽  
Functional Role ◽  
Micro Rna ◽  
Alcoholic Liver Injury

scholarly journals The role of oxidative stress in alcoholic liver injury

2009 ◽  
Vol 62 (11-12) ◽  
pp. 547-553 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Dusan Mladenovic ◽  
Danijela Vucevic
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Alcoholic Liver Injury ◽  
Chronic Ethanol Consumption

Introduction. Oxidative stress plays an important role in pathogenesis of alcoholic liver injury. The main source of free oxygen species is cytochrome P450-dependent monooxygenase, which can be induced by ethanol. Role of cytochrome P4502E1 in ethanol-induced oxidative stress. Reactive oxygen species produced by this enzyme are more important in intracellular oxidative damage compared to species derived from activated phagocytes. Free radicals lead to lipid peroxidation, enzymatic inactivation and protein oxidation. Role of mitochondria in alcohol-induced oxidative stress. Production of mitochondrial reactive oxygen species is increased, and glutathione content is decreased in chronically ethanolfed animals. Oxidative stress in mitochondria leads to mitochondrial DNA damage and has a dual effect on apoptosis. Role of Kupffer cells in alcohol-induced liver injury. Chronic ethanol consumption is associated with increased release of endotoxin from gut lumen into portal circulation. Endotoxin activates Kupffer cells, which then release proinflammatory cytokines and oxidants. Role of neutrophils in alcohol-induced liver injury. Alcoholic liver injury leads to the accumulation of neutrophils, which release reactive oxygen species and lysosomal enzymes and contribute to hepatocyte damage and necrosis. Role of nitric oxide in alcohol-induced oxidative stress. High amounts of nitric oxide contribute to the oxidative damage, mainly by generating peroxynitrites. Role of antioxidants in ethanol-induced oxidative stress. Chronic ethanol consumption is associated with reduced liver glutathione and ?-tocopherol level and with reduced superoxide dismutase, catalase and glutathione peroxidase activity. Conclusion. Oxidative stress in alcoholic liver disease is a consequence of increased production of oxidants and decreased antioxidant defense in the liver.

Role of Kupffer cells in failure of fatty livers following liver transplantation and alcoholic liver injury

1995 ◽  
Vol 10 (S1) ◽  
pp. S24-S30 ◽  
Author(s):  
RONALD G THURMAN ◽  
WENSHI GAO ◽  
HENRY D CONNOR ◽  
YUKITO ADACHI ◽  
ROBERT F STACHLEWITZ ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Injury ◽  
Kupffer Cells ◽  
Alcoholic Liver Injury ◽  
Fatty Livers

scholarly journals Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: Role of signal transducer and activator of transcription 3

Hepatology ◽  
2010 ◽  
Vol 52 (4) ◽  
pp. 1291-1300 ◽  
Author(s):  
Sung Hwan Ki ◽  
Oygi Park ◽  
Mingquan Zheng ◽  
Oriol Morales-Ibanez ◽  
Jay K. Kolls ◽  
...  
Keyword(s):  
Liver Injury ◽  
Murine Model ◽  
Alcoholic Liver Injury ◽  
Signal Transducer ◽  
Interleukin 22 ◽  
Ethanol Feeding ◽  
Transcription 3 ◽  
Binge Ethanol

Role of abnormal methionine metabolism in alcoholic liver injury

Alcohol ◽  
2002 ◽  
Vol 27 (3) ◽  
pp. 155-162 ◽  
Author(s):  
Shelly C Lu ◽  
Hidekazu Tsukamoto ◽  
José M Mato
Keyword(s):  
Liver Injury ◽  
Methionine Metabolism ◽  
Alcoholic Liver Injury

scholarly journals SIRT2-mediated deacetylation and deubiquitination of C/EBPβ prevents ethanol-induced liver injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yingting Zhang ◽  
Xidai Long ◽  
Xin Ruan ◽  
Qian Wei ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Liver Injury ◽  
Protein Expression ◽  
Nicotinamide Adenine Dinucleotide ◽  
Target Gene ◽  
Alcoholic Liver Injury ◽  
Protein Acetylation ◽  
Hepatocyte Apoptosis ◽  
Enhancer Binding Protein

AbstractProtein acetylation has emerged to play pivotal roles in alcoholic liver disease (ALD). Sirutin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase involved in the regulation of aging, metabolism, and stress. However, the role of SIRT2 in ALD remains unclear. Here, we report that the SIRT2-mediated deacetylation–deubiquitination switch of CCAAT/enhancer-binding protein beta (C/EBPβ) prevents ALD. Our results showed that hepatic SIRT2 protein expression was negatively correlated with the severity of alcoholic liver injury in ALD patients. Liver-specific SIRT2 deficiency sensitized mice to ALD, whereas transgenic SIRT2 overexpression in hepatocytes significantly prevented ethanol-induced liver injury via normalization of hepatic steatosis, lipid peroxidation, and hepatocyte apoptosis. Mechanistically, we identified C/EBPβ as a critical substrate of SIRT2 implicated in ALD. SIRT2-mediated deacetylation at lysines 102 and 211 decreased C/EBPβ ubiquitination, resulting in enhanced protein stability and subsequently increased transcription of C/EBPβ-target gene LCN2. Importantly, hepatic deacetylated C/EBPβ and LCN2 compensation reversed SIRT2 deletion-induced ALD aggravation in mice. Furthermore, C/EBPβ protein expression was positively correlated with SIRT2 and LCN2 expression in the livers of ALD patients and was inversely correlated with ALD development. Therefore, activating SIRT2-C/EBPβ-LCN2 signaling pathway is a potential therapy for ALD.

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