scholarly journals Ghrelin Alleviates Endoplasmic Reticulum Stress in MC3T3E1 Cells by Inhibiting AMPK Phosphorylation

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Xue Lv ◽  
Qianping Zhang ◽  
Bingfei Cheng ◽  
Ying Xin ◽  
Jun Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Energy Homeostasis ◽  
Marker Genes ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Expression Of Genes ◽  
Species Production ◽  
Related Proteins

Ghrelin is a gastric endocrine peptide that has been found to be involved in the process of energy homeostasis and bone physiology in recent years. To explore the effects of ghrelin on endoplasmic reticulum stress (ERS) in MC3T3E1 cells and its possible mechanism, an ERS model was induced by tunicamycin (TM) in the osteoblast line MC3T3E1. TM at 1.5 μg/mL was selected as the experimental concentration found by CCK8 assay. Through the determination of apoptosis, reactive oxygen species production, and endoplasmic reticulum stress-related gene expression, we found that ERS induced by TM can be relieved by ghrelin in a concentration-dependent manner ( P < 0.001 ). Compared with the TM group, ghrelin reduced the expression of ERS-related marker genes induced by TM. Compared with the GSK621 + TM group without ghrelin pretreatment, the mRNA expression of genes in the ghrelin pretreatment group decreased significantly ( P < 0.001 ). The results of protein analysis showed that the levels of BIP, p-AMPK, and cleaved-caspase3 in the TM group increased significantly, while the levels decreased after ghrelin pretreatment. In group GSK621 + TM compared with group GSK621 + ghrelin+TM, ghrelin pretreatment significantly reduced the level of p-AMPK, which is consistent with the trend of the ERS-related proteins BIP and cleaved-caspase3. In conclusion, ghrelin alleviates the ERS induced by TM in a concentration-dependent manner and may or at least partly alleviate the apoptosis induced by ERS in MC3T3E1 cells by inhibiting the phosphorylation of AMPK.

scholarly journals Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition

2017 ◽  
Vol 51 (1) ◽  
pp. 8-19 ◽  
Author(s):  
Minchenko Do ◽  
Riabovol Oo ◽  
Ratushna Oo ◽  
Minchenko Oh
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Quantitative Polymerase Chain Reaction ◽  
Glioma Cells ◽  
Hypoxic Condition ◽  
Enzyme Function ◽  
Unfolded Protein ◽  
Expression Of Genes ◽  
The Unfolded Protein Response ◽  
Related Proteins

Abstract Objective. The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation.Methods. The expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction.Results. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more significant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function.Conclusions. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes possibly contribute to the suppression of the cell proliferation. Most of these genes are regulated by hypoxia and preferentially through IRE1 signaling pathway of endoplasmic reticulum stress.

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 Glucose deprivation affects the expression of genes encoding cAMP-activated protein kinase and related proteins in U87 glioma cells in ERN1 dependent manner

2020 ◽  
Vol 54 (4) ◽  
pp. 244-254
Author(s):  
Oksana O. Ratushna
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Endoplasmic Reticulum Stress ◽  
Glioma Cells ◽  
Glucose Deprivation ◽  
Expression Level ◽  
Gene Expressions ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Related Proteins

Abstract Objective. The aim of this investigation was to study the expression of genes encoding cAMP-activated protein kinase catalytic and regulatory A subunits (PRKACA and PRKAR1A) and related proteins such as cAMP-dependent protein kinase inhibitors A and G (PKIA and PKIG), catalytic subunit A of protein phosphatase 3 (PPP3CA), A-kinase anchoring protein 12 (AKAP12), and praja ring finger ubiquitin ligase 2 (PJA2) in U87 glioma cells in response to glucose deprivation in both control U87 glioma cells and cells with ERN1 (endoplasmic reticulum to nucleus signaling 1) knockdown, the major pathway of the endoplasmic reticulum stress signaling, for evaluation of possible significance of glucose deprivation in ERN1 dependent regulation of glioma growth. Methods. The expression level of PRKA related genes was studied in control (transfected by vector) and ERN1 knockdown U87 glioma cells under glucose deprivation by real-time quantitative polymerase chain reaction. Results. It was shown that the expression level of PRKACA and PKIA genes was down-regulated in control glioma cells treated by glucose deprivation, but PJA2 gene was up-regulated. At the same time, the expression of four other genes (PRKAR1A, PKIG, AKAP12, and PPP3CA) was resistant to this experimental condition. Furthermore, ERN1 knockdown of glioma cells significantly modified the effect glucose deprivation on the expression almost all studied genes. Thus, treatment of glioma cells with inhibited ERN1 enzymatic activity by glucose deprivation lead to a more significant down-regulation of the expression level of PKIA and to suppression PRKAR1A gene expressions. Moreover, the ERN1 knockdown introduced up-regulation of PKIG and AKAP12 gene expressions in glioma cells treated by glucose deprivation and eliminated the sensitivity of PJA2 gene to this experimental condition. Conclusions. Results of this investigation demonstrated that ERN1 knockdown significantly modified the sensitivity of most studied PRKA related gene expressions to glucose deprivation and that these changes are a result of complex interactions of variable endoplasmic reticulum stress related and unrelated regulatory factors and contributed to the suppression of glioma cell proliferation and their possibly chemoresistance.

scholarly journals Naringin attenuates cerebral ischemia-reperfusion injury in rats by inhibiting endoplasmic reticulum stress

2021 ◽  
Vol 12 (1) ◽  
pp. 190-197
Author(s):  
Li Wang ◽  
Zhe Zhang ◽  
Haibin Wang
Keyword(s):  
Endoplasmic Reticulum ◽  
Brain Tissue ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Tissue Water Content ◽  
Tissue Water ◽  
Concentration Dependent Manner ◽  
Cerebral Ischemia Reperfusion ◽  
Tnf Α ◽  
Related Proteins

Abstract Objective This investigation was carried out with an aim of exploring neuroprotection by naringin (Nar) in rats with cerebral ischemia-reperfusion (CI/R) injury and its mechanism. Methods Rats were grouped into ischemia-reperfusion (I/R), sham operation (Sham), nimodipine control (NIM), and different doses of Nar (Nar-L, Nar-M, Nar-H) groups. With Zea Longa score for assessment of neurological deficits, dry and wet method for measurement of brain tissue water content, and (2,3,5-triphenyltetrazolium chloride) TTC staining for determination of cerebral infarction volume, the related parameters were obtained and compared. Subsequently, ELISA was introduced to detect levels of proinflammatory cytokines (TNF-α, IL-8) and anti-inflammatory cytokine (IL-10) in the serum as well as superoxide dismutase (SOD) and malondialdehyde (MDA) activities in brain tissue. Western blot was applied to evaluate endoplasmic reticulum stress (ERS)-related proteins expression, including glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12, and activating transcription factor 6 (ATF-6). Results Nar significantly alleviated nerve injury and decreased brain tissue water content and brain infraction volume in CI/R injury rats in a concentration-dependent manner. Reduction of TNF-α, IL-8 as well as MDA content and elevation of IL-10 as well as SOD activity were confirmed to be caused by Nar treatment in a concentration-dependent manner. Meanwhile, ERS-related proteins also markedly decreased in the Nar groups. Conclusion Nar may achieve neuroprotection and alleviation of CI/R injury by anti-inflammation, anti-oxidation, and inhibiting ERS, and its efficacy is concentration-dependent.

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 Albendazole reduces hepatic inflammation and endoplasmic reticulum-stress in a mouse model of chronic Echinococcus multilocularis infection

2022 ◽  
Vol 16 (1) ◽  
pp. e0009192
Author(s):  
Michael Weingartner ◽  
Simon Stücheli ◽  
Fadi Jebbawi ◽  
Bruno Gottstein ◽  
Guido Beldi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Echinococcus Multilocularis ◽  
Molecular Mechanisms ◽  
Disease Recurrence ◽  
Unfolded Protein ◽  
Programmed Death ◽  
Protein Response ◽  
Host Parasite ◽  
Related Proteins

Background Echinococcus multilocularis causes alveolar echinococcosis (AE), a rising zoonotic disease in the northern hemisphere. Treatment of this fatal disease is limited to chemotherapy using benzimidazoles and surgical intervention, with frequent disease recurrence in cases without radical surgery. Elucidating the molecular mechanisms underlying E. multilocularis infections and host-parasite interactions ultimately aids developing novel therapeutic options. This study explored an involvement of unfolded protein response (UPR) and endoplasmic reticulum-stress (ERS) during E. multilocularis infection in mice. Methods E. multilocularis- and mock-infected C57BL/6 mice were subdivided into vehicle, albendazole (ABZ) and anti-programmed death ligand 1 (αPD-L1) treated groups. To mimic a chronic infection, treatments of mice started six weeks post i.p. infection and continued for another eight weeks. Liver tissue was then collected to examine inflammatory cytokines and the expression of UPR- and ERS-related genes. Results E. multilocularis infection led to an upregulation of UPR- and ERS-related proteins in the liver, including ATF6, CHOP, GRP78, ERp72, H6PD and calreticulin, whilst PERK and its target eIF2α were not affected, and IRE1α and ATF4 were downregulated. ABZ treatment in E. multilocularis infected mice reversed, or at least tended to reverse, these protein expression changes to levels seen in mock-infected mice. Furthermore, ABZ treatment reversed the elevated levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in the liver of infected mice. Similar to ABZ, αPD-L1 immune-treatment tended to reverse the increased CHOP and decreased ATF4 and IRE1α expression levels. Conclusions and significance AE caused chronic inflammation, UPR activation and ERS in mice. The E. multilocularis-induced inflammation and consecutive ERS was ameliorated by ABZ and αPD-L1 treatment, indicating their effectiveness to inhibit parasite proliferation and downregulate its activity status. Neither ABZ nor αPD-L1 themselves affected UPR in control mice. Further research is needed to elucidate the link between inflammation, UPR and ERS, and if these pathways offer potential for improved therapies of patients with AE.

Effect of Metformin Intervention on Pancreatic β-Cell Apoptosis

2022 ◽  
Vol 12 (4) ◽  
pp. 873-877
Author(s):  
Dongqian Xie ◽  
Zhicheng Gao ◽  
Mei Liu ◽  
Defeng Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
High Glucose Condition ◽  
M Phase ◽  
Signaling Activation

Metformin is shown to have hypoglycemic effects. However, the relationship between metformin’s intervention in FFA-induced endoplasmic reticulum stress-mediated insulin resistance (IR) and insulin β-cell apoptosis under high-glucose condition remains unclear. Our study intends to assess their relationship. Human pancreatic β-cells were treated with metformin and cell proliferation and IR were detected by MTT assay along with detection of Wnt/β-catenin signaling by RT-PCR, cell cycle and apoptosis by flow cytometry. Metformin inhibited β cell proliferation which was mediated by FFA-induced endoplasmic reticulum stress in a time-dependent and dose-dependent manner as well as induced cell cycle arrest at G2/M phase. In addition, metformin inhibited β-catenin signaling activation and decreased the expression of c-myc, Dvl-2, survivin, Dvl-3, GSK-3β (p-ser9) and promoted GSK-3 (p-tyr216) and Axin-2 expression. In conclusion, metformin inhibits Wnt/β-catenin signaling and promotes FFA to induce endoplasmic reticulum stress, thereby mediating pancreatic β-cells behaviors.

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.

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