scholarly journals Hepatoprotective Effect of Quercetin on Endoplasmic Reticulum Stress and Inflammation after Intense Exercise in Mice through Phosphoinositide 3-Kinase and Nuclear Factor-Kappa B

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Yuhan Tang ◽  
Juan Li ◽  
Chao Gao ◽  
Yanyan Xu ◽  
Yanyan Li ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Liver Damage ◽  
Nuclear Translocation ◽  
Strenuous Exercise ◽  
Preventive Strategy ◽  
Intense Exercise ◽  
Activating Transcription Factor ◽  
Phosphoinositide 3 Kinase ◽  
Exercise Induced

The mechanisms underlying intense exercise-induced liver damage and its potential treatments remain unclear. We explored the hepatoprotection and mechanisms of quercetin, a naturally occurring flavonoid, in strenuous exercise-derived endoplasmic reticulum stress (ERS) and inflammation. Intense exercise (28 m/min at a 5° slope for 90 min) resulted in the leakage of aminotransferases in the BALB/C mice. The hepatic ultrastructural malformations and oxidative stress levels were attenuated by quercetin (100 mg/kg·bw). Intense exercise and thapsigargin- (Tg-) induced ERS (glucose-regulated protein 78, GRP78) and inflammatory cytokines levels (IL-6 and TNF-α) were decreased with quercetin. Furthermore, quercetin resulted in phosphoinositide 3-kinase (PI3K) induction, Ca2+restoration, and blockade of the activities of Jun N-terminal kinase (JNK), activating transcription factor 6 (ATF6) and especially NF-κB (p65 and p50 nuclear translocation). A PI3K inhibitor abrogated the protection of quercetin on ERS and inflammation of mouse hepatocytes. SP600125 (JNK inhibitor), AEBSF (ATF6 inhibitor), and especially PDTC (NF-κB inhibitor) enhanced the quercetin-induced protection against Tg stimulation. Collectively, intense exercise-induced ERS and inflammation were attenuated by quercetin. PI3K/Akt activation and JNK, ATF6, and especially NF-κB suppression were involved in the protection. Our results highlight a novel preventive strategy for treating ERS and inflammation-mediated liver damage induced by intense exercise using natural phytochemicals.

The effect of baicalein on endoplasmic reticulum stress and autophagy on liver damage

2021 ◽  
pp. 096032712110036
Author(s):  
MC Üstüner ◽  
C Tanrikut ◽  
D Üstüner ◽  
UK Kolaç ◽  
Z Özdemir Köroğlu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Er Stress ◽  
Liver Damage ◽  
Albino Rats ◽  
Tem Analysis ◽  
Stress Markers ◽  
Activating Transcription Factor 4 ◽  
Activating Transcription Factor ◽  
Wistar Albino Rats

Carbon tetrachloride (CCl4) is a toxic chemical that causes liver injury. CCl4 triggers endoplasmic reticulum (ER) stress and unfolded protein response (UPR). UPR triggers autophagy to deal with the damage. The aim of this study was to investigate the effect of baicalein, derived from Scutellaria baicalensis, on CCl4-induced liver damage concerning ER stress and autophagy. Two groups of Wistar albino rats (n = 7/groups) were treated with 0.2 ml/kg CCl4 for 10 days with and without baicalein. Histological and transmission electron microscopy (TEM) analysis, autophagy, and ER stress markers measurements were carried out to evaluate the effect of baicalein. Histological examinations showed that baicalein reduced liver damage. TEM analysis indicated that baicalein inhibited ER stress and triggered autophagy. CCl4-induced elevation of C/EBP homologous protein (CHOP), glucose-regulating protein 78 (GRP78), activating transcription factor 4 (ATF4), activating transcription factor 6 (ATF6), inositol requiring enzyme 1 (IRE1), pancreatic ER kinase (PERK), and active/spliced form of X-box-binding protein 1 (XBP1s) ER stress markers were decreased by baicalein. Baicalein also increased the autophagy-related 5 (ATG5), Beclin1, and Microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine-conjugated form (LC3-II) autophagy marker levels. In conclusion, baicalein reduced the CCl4-induced liver damage by inhibiting ER stress and the trigger of autophagy.

scholarly journals Ginsenoside Rg1 Prevents Doxorubicin-Induced Cardiotoxicity through the Inhibition of Autophagy and Endoplasmic Reticulum Stress in Mice

2018 ◽  
Vol 19 (11) ◽  
pp. 3658 ◽  
Author(s):  
Zhi-Meng Xu ◽  
Cheng-Bin Li ◽  
Qing-Ling Liu ◽  
Ping Li ◽  
Hua Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Role ◽  
Primary Component ◽  
Signal Pathways ◽  
Ginsenoside Rg1 ◽  
Cellular Signal ◽  
Pre Treatment ◽  
Activating Transcription Factor ◽  
Doxorubicin Group

Ginsenoside Rg1, a saponin that is a primary component of ginseng, has been demonstrated to protect hearts from diverse cardiovascular diseases with regulating multiple cellular signal pathways. In the present study, we investigated the protective role of ginsenoside Rg1 on doxorubicin-induced cardiotoxicity and its effects on endoplasmic reticulum stress and autophagy. After pre-treatment with ginsenoside Rg1 (50 mg/kg i.g.) for 7 days, male C57BL/6J mice were intraperitoneally injected with a single dose of doxorubicin (6 mg/kg) every 3 days for four injections. Echocardiographic and pathological findings showed that ginsenoside Rg1 could significantly reduce the cardiotoxicity induced by doxorubicin. Ginsenoside Rg1 significantly inhibited doxorubicin-induced formation of autophagosome. At the same time, ginsenoside Rg1 decreased the doxorubicin-induced cardiac microtubule-associated protein-light chain 3 and autophagy related 5 expression. Ginsenoside Rg1 can reduce endoplasmic reticulum dilation caused by doxorubicin. Compared with the doxorubicin group, the expression of cleaved activating transcription factor 6 and inositol-requiring enzyme 1 decreased in group ginsenoside Rg1. Treatment with ginsenoside Rg1 reduces the expression of TIF1 and increases the expression of glucose-regulated protein 78. In the ginsenoside Rg1 group, the expression of p-P70S6K, c-Jun N-terminal kinases 1 and Beclin1 declined. These results indicate that ginsenoside Rg1 may improve doxorubicin-induced cardiac dysfunction by inhibiting endoplasmic reticulum stress and autophagy.

Chrysophanol Triggers Cell Death via Unfolded Protein Response and Endoplasmic Reticulum Stress in Oral Cancer FaDu Cells

2020 ◽  
Vol 19 (1) ◽  
pp. 64-68
Author(s):  
Chih-Hung Lin ◽  
Ping-Hsun Lu ◽  
Chung-Tai Yue ◽  
Po-Chun Hsieh ◽  
Ya-Hsuan Lin ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Oral Cancer ◽  
Endoplasmic Reticulum Stress ◽  
Unfolded Protein Response ◽  
Protein C ◽  
Unfolded Protein ◽  
Homologous Protein ◽  
Activating Transcription Factor ◽  
Protein Response

Oral cancer is a type of head and neck cancer that can be life threatening. Unfolded protein response and endoplasmic reticulum stress play a critical role in carcinogenesis. However, prolonged activation of unfolded protein response also activates apoptosis. Thus, a new treatment strategy maybe activation of extensive unfolded protein response and severe endoplasmic reticulum stress in tumor cells. We examined the pharmacological effects of chrysophanol on an oral cancer cell line FaDu, a hypopharyngeal squamous cell carcinoma specifically for its ability to cause cell death via unfolded protein response and endoplasmic reticulum stress. We measured the expression of binding immunoglobulin protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1α, and activating transcription factor 6 after treatment with chrysophanol in absence or presence of APY29 (an inhibitor of phosphorylated inositol-requiring enzyme-1α). Chrysophanol caused cell death via upregulations of binding immunoglobulin protein that is also known as 78-kDa glucose-regulated protein, C/EBP homologous protein, phosphorylated inositol-requiring enzyme-1α, and activating transcription factor 6. This activity was reversed by APY29. Thus, chrysophanol could be a useful antitumor agent for the management of oral cancer.

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