114 ENDOPLASMIC RETICULUM (ER) STRESS IN HYPOXIA-INDUCED DIABETES MELLITUS MODEL

2016 ◽  
Vol 28 (2) ◽  
pp. 187
Author(s):  
C. Ahn ◽  
D. Lee ◽  
K. P. Kim ◽  
M. H. Lee ◽  
E.-B. Jeung
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Pancreatic Beta Cells ◽  
Hypoxic Condition ◽  
Protein Translation ◽  
Ion Concentration ◽  
Cellular Stress Response ◽  
Stress Markers ◽  
Calbindin D9k

Endoplasmic reticulum (ER) regulates calcium ion concentration as a reservoir in the cell. ER stress is a cellular stress response related to the endoplasmic reticulum. At the initial stage of ER stress, ER tries to restore normal function by halting protein translation, degrading misfolded proteins, and increasing production of chaperones involved in protein folding. If ER fails to restore ER stress, ER stress can lead cells to apoptosis. To study the signaling between ER stress and calcium channels under ER-stressed circumstances, we designed a hypoxia-induced diabetic model. Nine-week-old male mice were chosen, maintained under hypoxic condition under 10% O2, 5% CO2 for 10 days, and the expression of ER stress markers and calcium channel gene expression were examined by real-time PCR. By maintaining hypoxic condition, the mice showed high glucose levels. Under this diabetic condition, in pancreatic beta cells, ER stress markers were elevated. This tendency showed an increase in calbindin-D9k KO mice. Chaperones such as calreticulin and calnexin were decreased, but in calbindin-D9k KO mice chaperone calnexin was not decreased. Interestingly, the calbindin-D9k KO normoxia mice showed increased glucose level compared with wild-type normoxia mice. Also, calnexin expression of pancreas was decreased in calbindin-D9k KO normoxia mice. This result indicates that pancreas cells were under endoplasmic reticulum stress. Taken together, calbindin may play an important role in endoplasmic reticulum stress in pancreas. This work was supported by the National Research Foundation of Korea (NRF) grant of Korean government (MEST) (No. 2013-010514).

scholarly journals Plant Bioactive Molecules Reduces Endoplasmic Reticulum Stress in Liver and Adipose Tissue of Obese Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 482-482
Author(s):  
Ivan Torre-Villalvazo ◽  
Armando Tovar ◽  
Claudia Tovar-Palacio ◽  
Nimbe Torres ◽  
Erik Alejandro Torre ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Adipose Tissue ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Low Dose ◽  
Control Diet ◽  
Bioactive Molecules ◽  
Obese Mice ◽  
Funding Sources ◽  
Stress Markers

Abstract Objectives To determine if diferent plant bioactive compounds can ammelirate endoplasmic reticulum stress markers in liver and adipose tissue of obese mice and mice administered with a low dose of tunicamicin. Methods C57BL6 mice were fed a control diet (7% fat) or a high-fat diet (21% fat) with and without genistein or resveratrol supplementation (0.1%) for 12 weeks. Pharmacologic ER stress was induced in mice fed the control diet by an ip injection of a low dose of tunicamycin and euthanized 8 or 24 h after tunicamycin administration. Adipose tissues and liver were harvested to determine the abundance of ER stress markers by western blot and real time PCR. Results Genistein and resveratrol reduced the abundance of phospho JNK and phospho PERK in liver and subcutaneous adipose tissue of obese mice and lean mice administered with tunicamycin. Both polyphenols increased the mRNA abundance of XBP1s and BiP and reduced that of CHOP in both organs. These changes in proten phosphorylation and gene expression were accompanied with reduced hepatic steatosis and adipocyte hypertrophy. Conclusions The supplementation with plant polyphenols such as genistein or resveratrol reduced ER stress markers in liver and adipose tissue of obese mice and lean mice administerd with tunicamycin. Funding Sources This work is supported by a grant from CONACYT, Mexico to ITV Grant No. A1-S-41,077.

scholarly journals sFlt-1 (sVEGFR1) induces placental endoplasmic reticulum stress in trophoblast cell: implications for the complications in preeclampsia- an in vitro study

2017 ◽  
Author(s):  
Sankat Mochan ◽  
Manoj Kumar Dhingra ◽  
Betsy Varghese ◽  
Sunil Kumar Gupta ◽  
Shobhit saxena ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Sandwich Elisa ◽  
Maternal Serum ◽  
Trophoblast Cells ◽  
Maternal Circulation ◽  
Stress Markers ◽  
Apoptotic Protein

AbstractBackgroundThe concentration of sFlt-1, a major anti-angiogenic protein in maternal circulation has been seen to be raised in preeclamptic pregnancies. Endoplasmic reticulum (ER) stress represents one of the three (immunological, oxidative and ER stress) major stresses which placenta undergoes during pregnancies. The present study is designed to investigate the role of sFlt-1 in induction of ER stress in trophoblast cells.Materials and MethodsMaternal serum levels of anti-angiogenic protein sFlt-1 and central regulator of unfolded protein response GRP78 was measured using sandwich ELISA. The expression of various ER stress markers (GRP78, eIF2α, XBP1, ATF6 and apoptotic protein CHOP) were analyzed depending on various treatments given to the trophoblast cells using Immunofluorescence, western blot and q-RT PCR.ResultsIncreased expression of ER stress markers (GRP78, eIF2α, XBP1 ATF6 and apoptotic protein CHOP) was detected in the placental trophoblast cells treated with raised concentration of sFlt-1.ConclusionSignificant upregulated expression of ER stress markers in trophoblast cells exposed with increased concentration of sFlt-1 suggested that it may be one of the anti-angiogenic factors present in maternal sera which not only contributes to oxidative stress but also may cause endoplasmic reticulum stress.

scholarly journals Interplay between endoplasmic reticulum stress and non-coding RNAs in cancer

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Tianming Zhao ◽  
Juan Du ◽  
Hui Zeng
Keyword(s):  
Gene Expression ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Cancer Cells ◽  
Protein Translation ◽  
Nutritional Deficiencies ◽  
Tumor Stem Cell ◽  
Aberrant Expression ◽  
Non Coding Rnas

AbstractTo survive, cancer cells are subjected to various internal and external adverse factors, including genetic mutations, hypoxia, nutritional deficiencies, and drug toxicity. All of these factors result in the accumulation of unfolded proteins in the endoplasmic reticulum, which leads to a condition termed endoplasmic reticulum stress (ER stress) and triggers the unfolded protein response (UPR). UPR downstream components strictly control transcription and translation reprogramming to ensure selective gene expression, including that of non-coding RNA (ncRNAs), to adapt to adverse environments. NcRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating target gene expression and protein translation, and their aberrant expression is related to tumor development. Dysregulation of ncRNAs is involved in the regulation of various cellular characteristics of cancer cells, including growth, apoptosis, metastasis, angiogenesis, drug sensitivity, and tumor stem cell properties. Notably, ncRNAs and ER stress can regulate each other and collaborate to determine the fate of tumor cells. Therefore, investigating the interaction between ER stress and ncRNAs is crucial for developing effective cancer treatment and prevention strategies. In this review, we summarize the ER stress-triggered UPR signaling pathways involved in carcinogenesis followed by the mutual regulation of ER stress and ncRNAs in cancer, which provide further insights into the understanding of tumorigenesis and therapeutic strategies.

scholarly journals Mito-TEMPO Alleviates Renal Fibrosis by Reducing Inflammation, Mitochondrial Dysfunction, and Endoplasmic Reticulum Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqing Liu ◽  
Yundan Wang ◽  
Wei Ding ◽  
Yingdeng Wang
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Endoplasmic Reticulum ◽  
Kidney Disease ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Renal Fibrosis ◽  
Oxidative Stress Markers ◽  
Stress Markers

Background. Renal fibrosis is a common pathological symptom of chronic kidney disease (CKD). Many studies support that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are implicated in the pathogenesis of CKD. In our study, we investigated the benefits and underlying mechanisms of Mito-TEMPO on renal fibrosis in 5/6 nephrectomy mice. Methods. Mice were randomly divided into five groups as follows: control group, CKD group, CKD + Mito-TEMPO (1 mg·kg−1·day−1) group, CKD + Mito-TEMPO (3 mg·kg−1·day−1) group, and Mito-TEMPO group (3 mg·kg−1·day−1). Renal fibrosis was evaluated by PAS, Masson staining, immunohistochemistry, and real-time PCR. Oxidative stress markers such as SOD2 activity and MDA level in serum and isolated mitochondria from renal tissue were measured by assay kits. Mitochondrial superoxide production was evaluated by MitoSOX staining and Western blot. Mitochondrial dysfunction was assessed by electron microscopy and real-time PCR. ER stress-associated protein was measured by Western blot. Results. Impaired renal function and renal fibrosis were significantly improved by Mito-TEMPO treatment. Furthermore, inflammation cytokines, profibrotic factors, oxidative stress markers, mitochondrial dysfunction, and ER stress were all increased in the CKD group. However, these effects were significantly ameliorated in the Mito-TEMPO treatment group. Conclusions. Mito-TEMPO ameliorates renal fibrosis by alleviating mitochondrial dysfunction and endoplasmic reticulum stress possibly through the Sirt3-SOD2 pathway, which sheds new light on prevention of renal fibrosis in chronic kidney disease.

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 EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1198
Author(s):  
Juliana Gomez ◽  
Zammam Areeb ◽  
Sarah F. Stuart ◽  
Hong P. T. Nguyen ◽  
Lucia Paradiso ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Viability ◽  
Er Stress ◽  
Cell Survival ◽  
Glioblastoma Cells ◽  
Over Expression ◽  
Stress Markers ◽  
Apoptotic Protein ◽  
Novel Association ◽  
Reduced Activity

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.

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 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 Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

2009 ◽  
Vol 30 (7) ◽  
pp. 928-928
Author(s):  
Guenther Boden ◽  
Matthew Silviera ◽  
Brian Smith ◽  
Peter Cheung ◽  
Carol Homko
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Tissue Injury ◽  
Subcutaneous Fat ◽  
Whole Body ◽  
Monocyte Chemoattractant Protein 1 ◽  
Homologous Protein ◽  
Stress Markers ◽  
Acute Tissue Injury ◽  
Glucose Regulated Protein

Abstract Background It is not known whether acute tissue injury is associated with endoplasmic reticulum (ER) stress. Objective Our objective was to determine whether open, sc fat biopsies cause ER stress. Approach Five healthy subjects underwent three open sc fat biopsies. The first biopsy, taken from the lateral aspect of a thigh, was followed 4 h later by a second biopsy from the same incision site and a third biopsy from the contralateral leg. Expression markers of ER stress, inflammation, hypoxia, and adipokines were measured in these fat biopsies. In addition, we tested for signs of systemic ER stress and inflammation in plasma and in circulating monocytes. Results mRNA/18s ratios of IL-6, monocyte chemoattractant protein-1, CD-14, hypoxia-induced factor 1-α, the spliced form of Xbox protein-1, glucose-regulated protein 78, CEBP homologous protein, and activating factor-4 were all severalfold higher, whereas mRNA/18s ratios of adiponectin and leptin were lower in fat biopsies taken from the same site 4 h after the first biopsy but were unchanged in the second biopsy that was taken from the contralateral site. The biopsies were not associated with changes in plasma and monocyte IL-6 concentrations or in monocyte ER stress markers. Also, whole-body insulin-stimulated glucose uptake was the same in 15 subjects who had biopsies compared with 15 different subjects who did not. Conclusion Open, sc fat biopsies produced inflammation, hypoxia, ER stress, and decreased expression of adiponectin and leptin. These changes remained confined to the biopsy site for at least 4 h.

scholarly journals Attenuation of endoplasmic reticulum stress by caffeine ameliorates hyperoxia-induced lung injury

2017 ◽  
Vol 312 (5) ◽  
pp. L586-L598 ◽  
Author(s):  
Ru-Jeng Teng ◽  
Xigang Jing ◽  
Teresa Michalkiewicz ◽  
Adeleye J. Afolayan ◽  
Tzong-Jin Wu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lung Injury ◽  
Er Stress ◽  
Saline Control ◽  
Sprague Dawley ◽  
Chemical Chaperone ◽  
Stress Markers ◽  
Rat Pups ◽  
Caffeine Treatment ◽  
Downstream Effectors

Rodent pups exposed to hyperoxia develop lung changes similar to bronchopulmonary dysplasia (BPD) in extremely premature infants. Oxidative stress from hyperoxia can injure developing lungs through endoplasmic reticulum (ER) stress. Early caffeine treatment decreases the rate of BPD, but the mechanisms remain unclear. We hypothesized that caffeine attenuates hyperoxia-induced lung injury through its chemical chaperone property. Sprague-Dawley rat pups were raised either in 90 (hyperoxia) or 21% (normoxia) oxygen from postnatal day 1 (P1) to postnatal day 10 (P10) and then recovered in 21% oxygen until P21. Caffeine (20 mg/kg) or normal saline (control) was administered intraperitoneally daily starting from P2. Lungs were inflation-fixed for histology or snap-frozen for immunoblots. Blood caffeine levels were measured in treated pups at euthanasia and were found to be 18.4 ± 4.9 μg/ml. Hyperoxia impaired alveolar formation and increased ER stress markers and downstream effectors; caffeine treatment attenuated these changes at P10. Caffeine also attenuated the hyperoxia-induced activation of cyclooxygenase-2 and markers of apoptosis. In conclusion, hyperoxia-induced alveolar growth impairment is mediated, in part, by ER stress. Early caffeine treatment protects developing lungs from hyperoxia-induced injury by attenuating ER stress.

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