scholarly journals Sevoflurane modulates AQPs (1,5) expression and endoplasmic reticulum stress in mice lung with allergic airway inflammation

2019 ◽  
Vol 39 (11) ◽  
Author(s):  
Chang-Ming Lv ◽  
Hui-Mei Wu ◽  
Ling Wu ◽  
Guang-Hong Xu ◽  
Zhi-Lai Yang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Airway Inflammation ◽  
Inflammatory Diseases ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Mrna Levels ◽  
Protein Levels ◽  
Factor Α

Abstract Sevoflurane was found to show protective roles in mice with asthma, however, the mechanism of which needs further exploring. Aquaporins (AQPs) have been demonstrated to be involved in the pathogenesis of asthma, while endoplasmic reticulum stress has been reported to be related to many inflammatory diseases and involved in protein processing, including AQPs. The present study aimed to determine the role of sevoflurane in AQPs (AQP1,3,4,5) expression in mice with allergic airway inflammation and the probable mechanism. The increased number of inflammatory cells infiltrating the lung tissue, and the elevated levels of tumor necrosis factor-α (TNF-α) and interleukin (IL) 13 (IL-13) were all decreased after sevoflurane treatment (all P<0.05). Meanwhile, mRNA levels of AQP1 and AQP5 but not AQP3 and AQP4 were decreased in ovalbumin (OVA)-induced allergic mice lung. Both the decreased mRNA expression and protein levels of AQP1 and AQP5 in allergic lung tissues were reversed by sevoflurane treatment. Furthermore, we established that sevoflurane inhibited the OVA-induced protein increase in the endoplasmic reticulum (ER) stress markers BiP and C/EBP homologous protein (CHOP). Collectively, these findings suggested that sevoflurane modulated the expression and protein level of AOPs (AQP1, AQP5) as well as inhibited ER stress response in OVA-induced allergic airway inflammation of mice.

scholarly journals Exogenous acylated ghrelin promotes but un-acylated ghrelin prevents hepatic steatosis by modulating peripheral insulin resistance and hepatic oxidative and endoplasmic reticulum stress

2021 ◽  
Vol 7 (3) ◽  
Keyword(s):  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
Fatty Acid Synthase ◽  
Lipid Synthesis ◽  
Acylated Ghrelin ◽  
Mrna Levels ◽  
Protein Levels

Objectives: This study tested the effects of acylated (AG and un-acylated ghrelin (UAG) on hepatic lipid synthesis and insulin resistance (IR) from prospective to their effect on endoplasmic reticulum stress and investigated the possible underlying mechanisms. Methods: Healthy rats were divided as 4 groups (n=12/each) as control, control + AG, control + UAG, and control + AG + UAG (1:1). GA or UAG were given subcutaneously (200 ng/kg/each) for 8 weeks. Results: AG increased fasting levels of glucose and insulin resistance, increased hepatic glucose production, and impaired glucose and insulin tolerance. Besides, it increased serum levels of free fatty acids (FFAs), enhanced serum and hepatic levels of triglycerides and cholesterol, and increased lipid deposition in the livers of rats. Concomitantly, it stimulated the mRNA levels of SREBP1/2, fatty acid synthase, and protein levels of all arms of ER stress including Xbp-1, CHOP, ATF-6, and p-eIF2α, thus activating lipid synthesis and ER stress. It also reduced protein levels of p-IRS (Tyr612), p-Akt (Ser307), and increased levels of ROS, TNF-α, IL-6, and protein levels of cleaved caspase-12, p-IRS (Ser307), and p-JNK (The183/Tyr186) in rats’ livers. Administration of UAG alone or in combination with AG produced contradictory effects. However, both AG and UAG significantly increased mRNA levels of AMPK and PPARα suggesting FAs oxidation. Conclusion: AG induces hepatic steatosis and suppresses hepatic insulin signaling mainly by inducing peripheral IR that is associated with hepatic oxidative stress, inflammation, and ER stress. However, UAG alone or in combination exerts opposite effects.

scholarly journals Endoplasmic Reticulum Stress Is Involved in Baicalin Protection on Chondrocytes From Patients With Osteoarthritis

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881063 ◽  
Author(s):  
Jiangang Cao ◽  
Yu Zhang ◽  
Tianyi Wang ◽  
Bo Li
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Viability ◽  
Er Stress ◽  
Messenger Rna ◽  
Cell Counting ◽  
Protective Effects ◽  
Gene Expressions ◽  
Protein Levels

Osteoarthritis (OA) affects elderly population worldwide and endoplasmic reticulum (ER) stress is known to be positively correlated with OA development. Previous reports prove the cytoprotective effects of baicalin on chondrocytes, whereas the mechanisms are hardly reported. Hence, we aimed to investigate the links between OA, ER stress, and baicalin. Chondrocytes from patients with OA were subjected to H2O2 treatment with or without baicalin pretreatment, and cell viability was assessed via Cell Counting Kit-8. Messenger RNA (mRNA) amounts of apoptosis-related genes (Bax, Bcl-2, and Caspase-3), extracellular matrix (ECM)-related genes (Collange I, Collange II, Aggrecan, and Sox9) and ER stress hallmarks (binding immunoglobulin protein [BiP] C/EBP homologous protein [CHOP]) were evaluated via quantitative real-time PCR. Bax, Bcl-2, BiP, and CHOP protein levels were analyzed via Western blot. Baicalin suppressed the changes in cell viability and apoptosis-related gene expressions caused by H2O2. Reactive oxygen species and glutathione/oxidized glutathione assay showed that H2O2 enhanced oxidative stress. Baicalin suppressed H2O2-induced downregulation of mRNA expression of ECM-related genes. Moreover, baicalin reduced H2O2-stimulated increase in oxidative stress and the expression of ER stress hallmarks. Endoplasmic reticulum stress inducer abolished the protective activities, whereas ER stress inhibitor did not exhibit extra protective effects. Baicalin pretreatment protected patient-derived chondrocytes from H2O2 through ER stress inhibition.

scholarly journals Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Yi-Ming Li ◽  
Shao-Yang Zhao ◽  
Huan-Huan Zhao ◽  
Bao-Hua Wang ◽  
Sai-Mei Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Hepg2 Cells ◽  
Cellular Injury ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Protein Levels ◽  
Caspase 1 ◽  
The Metabolic Syndrome

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1α as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKα/β, p-NF-κB p65, NLRP3, cleaved caspase 1, and mature IL-1β occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1β pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD.

scholarly journals Endoplasmic Reticulum Stress Promotes The Release of Exosomal PD-L1 From Head and Neck Cancer Cells and Facilitates M2 Macrophage Differentiation

2021 ◽  
Author(s):  
Yi Yuan ◽  
Pengfei Jiao ◽  
Zeyu Wang ◽  
Mengqi Chen ◽  
Hongming Du ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Immune Surveillance ◽  
M2 Macrophage ◽  
Macrophage Differentiation ◽  
Poor Overall Survival ◽  
Macrophage Polarisation ◽  
Protein Levels

Abstract Background Endoplasmic reticulum stress (ER stress) fosters cancer cell escape from immune surveillance and upregulate PD-L1 expression, but the mechanisms remain unclear. Methods We analyzed protein levels by immunofluorescence and Western blotting, RNA levels by qRT-PCR. Exosomes were injected intravenously through the tail vein into 6-week-old nude mice once every other day for a total of 10 injections Results Expression of some ER stress markers, including GRP78 (glucose-regulated protein 78), ATF6 (activating transcription factor 6) and PERK (PKR-like endoplasmic reticulum kinase), was upregulated in OSCC tissues and correlated with poor overall survival. The level of ER stress-related proteins positively correlated with a cluster of PD-L1 expression and macrophage infiltration in OSCC tissues. PD-L1 expression in OSCC tissues was negatively correlated with cumulative survival. Incubation with Exo-ER upregulated PD-L1 levels in macrophages in vitro and vivo, and upregulation of PD-L1 promoted macrophage polarisation towards the M2 subtype. Conclusions ER stress induced exosome secretion by OSCC cells and PD-L1 expression in macrophages to promote M2 macrophage differentiation. A novel exosome-modulated mechanism was delineated for OSCCs-macropahge crosstalk that drove tumor growth and should be explored for its therapeutic utility.

Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

2019 ◽  
Vol 19 (5) ◽  
pp. 665-675 ◽  
Author(s):  
Wenjiao Shi ◽  
Zhixin Guo ◽  
Ruixia Yuan
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Protective Effect ◽  
Er Stress ◽  
B Cell Lymphoma ◽  
Diabetic Rats ◽  
Pathological Changes ◽  
Rapamycin Treatment ◽  
Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

scholarly journals Different Expression of Mitochondrial and Endoplasmic Reticulum Stress Genes in Epicardial Adipose Tissue Depends on Coronary Atherosclerosis

2021 ◽  
Vol 22 (9) ◽  
pp. 4538
Author(s):  
Helena Kratochvílová ◽  
Miloš Mráz ◽  
Barbora J. Kasperová ◽  
Daniel Hlaváček ◽  
Jakub Mahrík ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mrna Expression ◽  
Coronary Atherosclerosis ◽  
Stress Genes ◽  
Valvular Surgery

The aim of our study was to analyze mitochondrial and endoplasmic reticulum (ER) gene expression profiles in subcutaneous (SAT) and epicardial (EAT) adipose tissue, skeletal muscle, and myocardium in patients with and without CAD undergoing elective cardiac surgery. Thirty-eight patients, 27 with (CAD group) and 11 without CAD (noCAD group), undergoing coronary artery bypass grafting and/or valvular surgery were included in the study. EAT, SAT, intercostal skeletal muscle, and right atrium tissue and blood samples were collected at the start and end of surgery; mRNA expression of selected mitochondrial and ER stress genes was assessed using qRT-PCR. The presence of CAD was associated with decreased mRNA expression of most of the investigated mitochondrial respiratory chain genes in EAT, while no such changes were seen in SAT or other tissues. In contrast, the expression of ER stress genes did not differ between the CAD and noCAD groups in almost any tissue. Cardiac surgery further augmented mitochondrial dysfunction in EAT. In our study, CAD was associated with decreased expression of mitochondrial, but not endoplasmic reticulum stress genes in EAT. These changes may contribute to the acceleration of coronary atherosclerosis.

scholarly journals Molecular functions of ASK family in diseases caused by stress-induced inflammation and apoptosis

2020 ◽  
Author(s):  
Kazuki Kojima ◽  
Hidenori Ichijo ◽  
Isao Naguro
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Adverse Effects ◽  
Er Stress ◽  
Inflammatory Diseases ◽  
Family Members ◽  
Disease States ◽  
Molecular Functions ◽  
Critical Responses ◽  
Proper Response

Summary VCells are constantly exposed to various types of stress, and disruption of the proper response lead to a variety of diseases. Among them, inflammation and apoptosis are important examples of critical responses and should be tightly regulated, as inappropriate control of these responses is detrimental to the organism. In several disease states, these responses are abnormally regulated, with adverse effects. Apoptosis signal-regulating kinase (ASK) family members are stress-responsive kinases that regulate inflammation and apoptosis after a variety of stimuli, such as oxidative stress and endoplasmic reticulum (ER) stress. In this review, we summarize recent reports on the ASK family in terms of their involvement in inflammatory diseases, focusing on upstream stimuli that regulate ASK family members.

scholarly journals Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark

Diabetologia ◽  
2021 ◽  
Author(s):  
Juliana de Almeida-Faria ◽  
Daniella E. Duque-Guimarães ◽  
Thomas P. Ong ◽  
Lucas C. Pantaleão ◽  
Asha A. Carpenter ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Maternal Obesity ◽  
Luciferase Assay ◽  
Whole Body ◽  
Mrna Levels ◽  
Protein Levels ◽  
Novel Targets

Abstract Aims/hypothesis Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. Methods miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic–hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. Results The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. Conclusions/interpretation Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target. Graphical abstract

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

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