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.

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 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.

Multidrug resistance protein expression of adult T-cell leukemia/lymphoma

2007 ◽  
Vol 31 (4) ◽  
pp. 465-470 ◽  
Author(s):  
Takeshi Yasunami ◽  
Yan-hua Wang ◽  
Kazue Tsuji ◽  
Minoko Takanashi ◽  
Yasuaki Yamada ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
T Cell ◽  
Protein Expression ◽  
Multidrug Resistance Protein ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Adult T Cell Leukemia ◽  
Resistance Protein

scholarly journals Hepatoprotective Effects of Different Extracts From Triphala Against CCl4-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Xichuan Wei ◽  
Chuanhong Luo ◽  
Yanan He ◽  
Haozhou Huang ◽  
Fei Ran ◽  
...  
Keyword(s):  
Liver Injury ◽  
Mouse Model ◽  
Protein Expression ◽  
Acute Liver Injury ◽  
Quinone Oxidoreductase ◽  
Tnf Α ◽  
Gene And Protein Expression ◽  
Wide Range ◽  
Hepatoprotective Effects ◽  
The Impact

Background:Triphala is a traditional polyherbal formula used in Indian Ayurvedic and Chinese Tibetan medicine. A wide range of biological activities have been attributed to Triphala, but the impact of various extraction methods on efficacy has not been determined.Purpose: The study aimed to evaluate Triphala extracts obtained by various methods for their hepatoprotective effects and molecular mechanisms in a mouse model of carbon tetrachloride (CCl4)-induced liver injury.Methods: HPLC fingerprinting was used to characterize the chemical characteristics of Triphala extracts obtained by (a) 0.5 h ultrasonication, (b) 2 h reflux, and (c) 4 h reflux. Hepatoprotective efficacy was evaluated in a mouse model of CCl4-induced liver damage. Serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured, as well as the liver antioxidant and inflammatory markers malondialdehyde superoxide dismutase glutathione peroxidase (GSH-Px), TNF-α, and IL-6. Gene and protein expression of Nrf-2 signaling components Nrf-2, heme oxygenase (HO-1), and NADPH Quinone oxidoreductase (NQO-1) in liver tissue were evaluated by real-time PCR and western blotting.Results: Chemical analysis showed a clear difference in content between extracts produced by ultrasonic and reflux methods. The pharmacological analysis showed that all three Triphala extracts reduced ALT, AST, MDA, TNF-α, and IL-6 levels and increased SOD and GSH-Px. Triphala extracts also induced transcript and protein expression of Nrf-2, HO-1, and NQO-1.Conclusion: Triphala extract prevents CCl4-induced acute liver injury. The ultrasonic extract of Triphala was most effective, suggesting that hepatoprotection may be related to the larger tannins via activation of Nrf-2 signaling.

Effects of age on multidrug resistance protein expression and doxorubicin accumulation in cardiac and skeletal muscle

Xenobiotica ◽  
2013 ◽  
Vol 44 (5) ◽  
pp. 472-479 ◽  
Author(s):  
Noah M. Gibson ◽  
Colin J. Quinn ◽  
Keith B. Pfannenstiel ◽  
David S. Hydock ◽  
Reid Hayward
Keyword(s):  
Skeletal Muscle ◽  
Multidrug Resistance ◽  
Protein Expression ◽  
Multidrug Resistance Protein ◽  
Resistance Protein

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.

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