988 - Aldose Reductase Null Mice are Protected Against Alcohol-Induced Hepatic ER Stress, Apoptosis and Liver Injury

2018 ◽  
Vol 154 (6) ◽  
pp. S-1111-S-1112
Author(s):  
Min Wang ◽  
Wei-Yang Chen ◽  
Leila Gobejishvili ◽  
Shirish Barve ◽  
Craig J. McClain ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Aldose Reductase

scholarly journals Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lixiang Wang ◽  
Xin Li ◽  
Yuki Hanada ◽  
Nao Hasuzawa ◽  
Yoshinori Moriyama ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Er Stress ◽  
Disease Progression ◽  
Acute Liver Injury ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Related Protein ◽  
Liver Disease Progression

AbstractMitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.

Inhibition of Endoplasmic Reticulum Stress Attenuated Ethanol-Induced Exosomal miR-122 and Acute Liver Injury in Mice

2019 ◽  
Vol 54 (5) ◽  
pp. 465-471 ◽  
Author(s):  
Sheng Wang ◽  
Jiajie Luan ◽  
Xiongwen Lv
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Hepatosomatic Index ◽  
Intragastric Administration ◽  
Alcoholic Liver Injury ◽  
Therapy Strategy ◽  
Related Proteins

ICR mice received ethanol (5 g/kg) by intragastric administration, showing an increase in hepatosomatic index and ALT. These effects were accompanied by increased expression of ER stress-related proteins and exosomal miR-122, PBA intervention can attenuate these changes induced by ethanol provides a potential therapy strategy for acute alcoholic liver injury.

scholarly journals Hepatic Transcriptome Analysis Revealing the Molecular Pathogenesis of Type 2 Diabetes Mellitus in Zucker Diabetic Fatty Rats

2020 ◽  
Vol 11 ◽  
Author(s):  
Chengdong Xia ◽  
Xiuli Zhang ◽  
Tianshu Cao ◽  
Jiannong Wang ◽  
Cuidan Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Liver Injury ◽  
Er Stress ◽  
Molecular Pathogenesis ◽  
Clinical Indices ◽  
Zdf Rats ◽  
Hepatic Transcriptome

Around 9% of the adult population in the world (463 million) suffer from diabetes mellitus. Most of them (~90%) belong to type 2 diabetes mellitus (T2DM), which is a common chronic metabolic disorder, and the number of cases has been reported to increase each year. Zucker diabetic fatty (ZDF) rat provides a successful animal model to study the pathogenesis of T2DM. Although previous hepatic transcriptome studies revealed some novel genes associated with the occurrence and development of T2DM, there still lacks the comprehensive transcriptomic analysis for the liver tissues of ZDF rats. We performed comparative transcriptome analyses between the liver tissues of ZDF rats and healthy ZCL rats and also evaluated several clinical indices. We could identify 214 and 104 differentially expressed genes (DEGs) and lncRNAs in ZDF rats, respectively. Pathway and biofunction analyses showed a synergistic effect between mRNAs and lncRNAs. By comprehensively analyzing transcriptomic data and clinical indices, we detected some typical features of T2DM in ZDF rats, such as upregulated metabolism (significant increased lipid absorption/transport/utilization, gluconeogenesis, and protein hydrolysis), increased inflammation, liver injury and increased endoplasmic reticulum (ER) stress. In addition, of the 214 DEGs, 114 were known and 100 were putative T2DM-related genes, most of which have been associated with substance metabolism (particularly degradation), inflammation, liver injury and ER stress biofunctions. Our study provides an important reference and improves understanding of molecular pathogenesis of obesity-associated T2DM. Our data can also be used to identify potential diagnostic markers and therapeutic targets, which should strengthen the prevention and treatment of T2DM.

scholarly journals Comparative Proteomic Identification of Protein Disulphide Isomerase A6 Associated with Tert-Butylhydroperoxide-Induced Liver Injury in Rat Hepatocytes

2018 ◽  
Vol 45 (5) ◽  
pp. 1915-1926 ◽  
Author(s):  
Chien-Heng Shen ◽  
Shui-Yi Tung ◽  
Wen-Shih Huang ◽  
Kam-Fai Lee ◽  
Yung-Yu Hsieh ◽  
...  
Keyword(s):  
Liver Injury ◽  
Cell Viability ◽  
Er Stress ◽  
Primary Cultures ◽  
Liver Cells ◽  
Cytochrome C Release ◽  
Dapi Staining ◽  
Tert Butylhydroperoxide

Background/Aims: Oxidants are important human toxicants. They have been implicated in the occurrence and development of liver diseases. Increased intracellular tert-butylhydroperoxide (t-BHP) may be critical for oxidant toxicity, and is commonly used for evaluating mechanisms involving oxidative stress, but the method remains controversial. Methods: Primary cultures of hepatocytes as well as human Hep G2 and mouse FL83B liver cells were obtained. Cell viability was measured by annexin V–FITC/propidium iodide and DAPI staining to determine the effects of t-BHP treatment on acute liver injury. A proteomic assay provided information that was used to identify the differentially expressed proteins following t-BHP treatment; immunohistochemistry and western blotting were performed to detect the expression of PDIA6 activity in apoptotic and endoplasmic reticulum (ER) stress pathways. Results: Our results demonstrate that t-BHP treatment of liver cells increased cell cytotoxicity and the generation of reactive oxygen species. This treatment also increased the level of PDIA6; this was validated in vitro and in vivo based on a comparison of t-BHP-treated and -untreated groups. Treatment of mouse liver FL83B cells with t-BHP activated caspase 3, increased the expression of apoptotic molecules, caused cytochrome c release, and induced Bcl-2, Bax and IRE1α/TRAF2 complex formation. t-BHP-dependent induction of apoptosis was accompanied by sustained phosphorylation of the IRE1α/ASK1/JNK1/2/p38 pathways and PDIA6 expression. Furthermore, t-BHP induced liver FL83B cell viability and apoptosis by upregulating the levels of PDIA6; this process could be involved in the activation of the IRE1α/ASK1/JNK1/2/p38 signalling pathways. Conclusions: We conclude that t-BHP induced an apoptosis cascade and ER stress in hepatocytes by upregulation of PDIA6, providing a new mechanism underlying the effects of t-BHP on liver injury.

Sa1456 - Molecular Mechanisms of PDE4 Inhibition on Alcohol-Induced ER Stress and Hepatocyte Survival in an Alcoholic Liver Injury Model

2018 ◽  
Vol 154 (6) ◽  
pp. S-1119
Author(s):  
Banrida Wahlang ◽  
Walter Rodriguez-Alvarez ◽  
Yali Wang ◽  
Jingwen Zhang ◽  
Shirish Barve ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Alcoholic Liver Injury ◽  
Injury Model

scholarly journals Activating transcription factor 6-dependent sestrin 2 induction ameliorates ER stress-mediated liver injury

2017 ◽  
Vol 1864 (7) ◽  
pp. 1295-1307 ◽  
Author(s):  
Kyung Hwan Jegal ◽  
Sang Mi Park ◽  
Sam Seok Cho ◽  
Sung Hui Byun ◽  
Sae Kwang Ku ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Liver Injury ◽  
Er Stress ◽  
Activating Transcription Factor

M1763 Differential Effects of Alcohol and Homocysteine On ER Stress Signaling and Liver Injury Between Mice and Rats

2008 ◽  
Vol 134 (4) ◽  
pp. A-413-A-414
Author(s):  
Masao Shinohara ◽  
TinAung Than ◽  
Christine Chan ◽  
Neil Kaplowitz ◽  
Cheng Ji
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Stress Signaling ◽  
Differential Effects

scholarly journals Scutellaria baicalensis Georgi extract protects against alcohol-induced acute liver injury in mice and affects the mechanism of ER stress

2016 ◽  
Vol 13 (4) ◽  
pp. 3052-3062 ◽  
Author(s):  
QINGQING DONG ◽  
FEI CHU ◽  
CHENGZHU WU ◽  
QIANG HUO ◽  
HUAIYONG GAN ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Scutellaria Baicalensis ◽  
Scutellaria Baicalensis Georgi

scholarly journals Down-Regulation of miR-212-5p Facilitates Homocysteine-Induced Hepatocytes Apoptosis Via Targeting PSMD10

2020 ◽  
Author(s):  
Huiping Zhang ◽  
Kun Xiao ◽  
Shengchao Ma ◽  
Long Xu ◽  
Ning Ding ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Down Regulation ◽  
Over Expression ◽  
Direct Binding ◽  
Induced Apoptosis ◽  
Insight Into

Abstract Background: Increasing evidences supported that elevated homocysteine (Hcy) levels contribute to cell apoptosis is implicated in the pathogenesis of liver injury, it correlates with liver disease severity. However, the underlying mechanism of apoptosis in Hcy-mediated liver injury remains obscure. Results: In this study, we found that homocysteine increases ER stress-mediated apoptosis and aggravates liver injury through up-regulation of PSMD10 expression in cbs+/- mice mice fed with high methionine diet and hepatocytes treated with homocysteine in vitro. Knockdown of PSMD10 expression remarkably reduced ER stress or apoptosis-associated protein in hepatocytes exposed to homocysteine. Moreover, bioinformatics analysis revealed that PSMD10 is a potential target gene of miR-212-5p, and luciferase reporter assay also confirmed that miR-212-5p negatively regulated PSMD10 expression by direct binding to its 3’-UTR regions. Subsequently, over-expression of miR-212-5p inhibited ER stress-mediated hepatocytes apoptosis though targeting PSMD10, all of which were abrogated by knockdown of miR-212-5p expression. Further study showed that the interaction between PSMD10 and GRP78 accelerated ER stress-mediated hepatic apoptosis induced by homocysteine. Conclusion: Taken together, these results demonstrated that down-regulation of miR-212-5p facilitates homocysteine-induced hepatocytes apoptosis via targeting PSMD10, which provides novel insight into the mechanism of homocysteine induced apoptosis in liver injury.

scholarly journals Linking Dysregulated AMPK Signaling and ER Stress in Ethanol-Induced Liver Injury in Hepatic Alcohol Dehydrogenase Deficient Deer Mice

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 560 ◽  
Author(s):  
Mukund Srinivasan ◽  
Kamlesh Bhopale ◽  
Samir Amer ◽  
Jie Wan ◽  
Lata Kaphalia ◽  
...  
Keyword(s):  
Liver Injury ◽  
Alcohol Dehydrogenase ◽  
Er Stress ◽  
Blood Alcohol Concentration ◽  
Alcohol Concentration ◽  
Deer Mice ◽  
Predisposing Factor ◽  
Ampk Signaling ◽  
Hepatic Lipids ◽  
Amp Activated Protein Kinase

Ethanol (EtOH) metabolism itself can be a predisposing factor for initiation of alcoholic liver disease (ALD). Therefore, a dose dependent study to evaluate liver injury was conducted in hepatic alcohol dehydrogenase (ADH) deficient (ADH−) and ADH normal (ADH+) deer mice fed 1%, 2% or 3.5% EtOH in the liquid diet daily for 2 months. Blood alcohol concentration (BAC), liver injury marker (alanine amino transferase (ALT)), hepatic lipids and cytochrome P450 2E1 (CYP2E1) activity were measured. Liver histology, endoplasmic reticulum (ER) stress, AMP-activated protein kinase (AMPK) signaling and cell death proteins were evaluated. Significantly increased BAC, plasma ALT, hepatic lipids and steatosis were found only in ADH− deer mice fed 3.5% EtOH. Further, a significant ER stress and increased un-spliced X-box binding protein 1 were evident only in ADH− deer mice fed 3.5% EtOH. Both strains fed 3.5% EtOH showed deactivation of AMPK, but increased acetyl Co-A carboxylase 1 and decreased carnitine palmitoyltransferase 1A favoring lipogenesis were found only in ADH− deer mice fed 3.5% EtOH. Therefore, irrespective of CYP2E1 overexpression; EtOH dose and hepatic ADH deficiency contribute to EtOH-induced steatosis and liver injury, suggesting a linkage between ER stress, dysregulated hepatic lipid metabolism and AMPK signaling.

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