scholarly journals Autophagy and ER stress in LPS/GalN-induced acute liver injury

2017 ◽  
Vol 16 (5) ◽  
pp. 7001-7005 ◽  
Author(s):  
Ting Shi ◽  
Weifang Song ◽  
Ruiling Xu
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Acute Liver Injury

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 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

Endoplasmic Reticulum Stress Increases Multidrug-resistance Protein 2 Expression and Mitigates Acute Liver Injury

2020 ◽  
Vol 20 (7) ◽  
pp. 548-557
Author(s):  
Wen-Ge Huang ◽  
Jun Wang ◽  
Yu-Juan Liu ◽  
Hong-Xia Wang ◽  
Si-Zhen Zhou ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Multidrug Resistance ◽  
Liver Injury ◽  
Protein Expression ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Multidrug Resistance Protein ◽  
Functional Involvement ◽  
Resistance Protein ◽  
The Impact

Background: Multidrug-resistance protein (MRP) 2 is a key membrane transporter that is expressed on hepatocytes and regulated by nuclear factor kappa B (NF-κB). Interestingly, endoplasmic reticulum (ER) stress is closely associated with liver injury and the activation of NF-κB signaling. Objective: Here, we investigated the impact of ER stress on MRP2 expression and the functional involvement of MRP2 in acute liver injury. Methods: ER stress, MRP2 expression, and hepatocyte injury were analyzed in a carbon tetrachloride (CCl4)-induced mouse model of acute liver injury and in a thapsigargin (TG)-induced model of ER stress. Results: CCl4 and TG induced significant ER stress, MRP2 protein expression and NF- κB activation in mice and LO2 cells (P < 0.05). Pretreatment with ER stress inhibitor 4- phenyl butyric acid (PBA) significantly mitigated CCl4 and TG-induced ER stress and MRP2 protein expression (P < 0.05). Moreover, pretreatment with pyrrolidine dithiocarbamic acid (PDTC; NF-κB inhibitor) significantly inhibited CCl4-induced NF-κB activation and reduced MRP2 protein expression (1±0.097 vs. 0.623±0.054; P < 0.05). Furthermore, hepatic downregulation of MRP2 expression significantly increased CCl4- induced ER stress, apoptosis, and liver injury. Conclusion: ER stress enhances intrahepatic MRP2 protein expression by activating NF-κB. This increase in MRP2 expression mitigates ER stress and acute liver injury.

scholarly journals ARRB1 suppresses the activation of hepatic macrophages via modulating endoplasmic reticulum stress in lipopolysaccharide-induced acute liver injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yiming Lei ◽  
Sizhe Wan ◽  
Huiling Liu ◽  
Haoxiong Zhou ◽  
Lingjun Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Er Stress ◽  
Cell Lines ◽  
Macrophage Activation ◽  
Acute Liver Injury ◽  
Vital Event ◽  
Hepatic Macrophages ◽  
Liver Macrophage ◽  
Hepatic Macrophage

AbstractAcute liver injury (ALI) caused by multiple inflammatory responses is a monocyte-/macrophage-mediated liver injury that is associated with high morbidity and mortality. Liver macrophage activation is a vital event that triggers ALI. However, the mechanism of liver macrophage activation has not been fully elucidated. This study examined the role of β-arrestin1 (ARRB1) in wild-type (WT) and ARRB1-knockout (ARRB1-KO) mouse models of ALI induced by lipopolysaccharide (LPS), and ARRB1-KO mice exhibited more severe inflammatory injury and liver macrophage activation compared to WT mice. We found that LPS treatment reduced the expression level of ARRB1 in Raw264.7 and THP-1 cell lines, and mouse primary hepatic macrophages. Overexpression of ARRB1 in Raw264.7 and THP-1 cell lines significantly attenuated LPS-induced liver macrophage activation, such as transformation in cell morphology and enhanced expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6), while downregulation of ARRB1 by small interfering RNA and ARRB1 deficiency in primary hepatic macrophages both aggravated macrophage activation. Moreover, overexpression of ARRB1 suppressed LPS-induced endoplasmic reticulum (ER) stress in liver macrophages, and inhibition of ER stress impeded excessive hepatic macrophage activation induced by downregulation of ARRB1. Our data demonstrate that ARRB1 relieves LPS-induced ALI through the ER stress pathway to regulate hepatic macrophage activation and that ARRB1 may be a potential therapeutic target for ALI.

scholarly journals Inhibition of eIF2α Dephosphorylation Protects Hepatocytes from Apoptosis by Alleviating ER Stress in Acute Liver Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Yong-Jing Tang ◽  
Huan Chen ◽  
Yu Yi ◽  
Gui-Mei Chen ◽  
Fang-Wan Yang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Initiation Factor ◽  
Calcium Balance ◽  
Hepatocyte Apoptosis ◽  
Protein Kinase R ◽  
Chemical Chaperone ◽  
Initiation Factor 2 ◽  
Phenylbutyric Acid

Objectives. Protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2α) is an important factor along the main pathways for endoplasmic reticulum (ER) stress-mediated apoptosis. In this study, we investigated the effects of eIF2α phosphorylation on hepatocyte apoptosis and the ER stress mechanisms in acute liver injury. Methods. eIF2α phosphorylation and apoptosis under ER stress were monitored and measured in male BALB/c mice with acute liver injury and human hepatocyte line LO2 cells. Results. Carbon tetrachloride (CCl4) administration triggered ER stress and hepatocyte apoptosis, as well as eIF2α phosphorylation in mice. Inhibition of eIF2α dephosphorylation, as the pretreatment with 4-phenylbutyric acid (chemical chaperone, ER stress inhibitor), mitigated CCl4-induced intrahepatic ER stress, apoptosis, and liver injury. In an ER stress model of LO2 cells induced by thapsigargin (disrupting ER calcium balance), inhibition of eIF2α dephosphorylation reduced ER stress and apoptosis, while PERK knockdown reduced eIF2α phosphorylation and exacerbated ER stress and apoptosis. Conclusions. eIF2α phosphorylation is one of the mechanisms employed by ER stress for restoring cellular homeostasis. Inhibition of eIF2α dephosphorylation mitigates hepatocyte apoptosis by alleviating ER stress in acute liver injuries.

Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis

2020 ◽  
Vol 168 (4) ◽  
pp. 365-374
Author(s):  
Shaoxun Li ◽  
Shuanghong Jin ◽  
Weilai Chen ◽  
Jiake Yu ◽  
Peipei Fang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Er Stress ◽  
Protein Level ◽  
Acute Liver Injury ◽  
Luciferase Reporter ◽  
Over Expression ◽  
Primary Mouse ◽  
Nrf2 Protein

Abstract This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3′-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

scholarly journals Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Mei-Ying Huang ◽  
Dian-Wei Wan ◽  
Jie Deng ◽  
Wen-Jie Guo ◽  
Yue Huang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Er Stress ◽  
Acute Liver Injury ◽  
Recovery Process ◽  
Regulatory Relationship ◽  
Negative Feedback Regulation ◽  
Injury Model ◽  
The Impact

Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

Aloe-Emodin Quinone Pretreatment Reduces Acute Liver Injury Induced by Carbon Tetrachloride

2000 ◽  
Vol 87 (5) ◽  
pp. 229-233 ◽  
Author(s):  
Beatrice Arosio ◽  
Nicoletta Gagliano ◽  
Lorena Maria Pia Fusaro ◽  
Luciano Parmeggiani ◽  
Jacopo Tagliabue ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Aloe Emodin
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