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ER stress

Seungwoo Kim, Hyosoon Cheon, Sam-Moon Kim, Young-Youl Kim
Background: Previous studies indicated that cadmium (Cd) increases PI3-kinase/Akt phosphorylation, resulting in an alteration in GSK-3β activity. However, the mechanism of Cd-induced endoplasmic reticulum (ER) stress in neuronal cells has yet to be studied in needs further elucidation. We examined the role of GSK-3β in Cd-induced neuronal cell death and the related downstream signaling pathways. Methods: SH-SY5Y human neuroblastoma cells were treated with 10 or 20 μM BAPTA-AM and 1 μM wortmannin for 30 min and then incubated with 25 μM Cd for 12 h...
2018: Cellular & Molecular Biology Letters
Oliver Edenharter, Stephan Schneuwly, Juan A Navarro
Friedreich's ataxia (FRDA) is the most important recessive ataxia in the Caucasian population. It is caused by a deficit of the mitochondrial protein frataxin. Despite its pivotal effect on biosynthesis of iron-sulfur clusters and mitochondrial energy production, little is known about the influence of frataxin depletion on homeostasis of the cellular mitochondrial network. We have carried out a forward genetic screen to analyze genetic interactions between genes controlling mitochondrial homeostasis and Drosophila frataxin...
2018: Frontiers in Molecular Neuroscience
Hongyang Quan, Qianqian Fan, Chuang Li, Yan-Ying Wang, Lin Wang
The unfolded protein response (UPR) is activated, when the folding capacity is compromised in the endoplasmic reticulum (ER). To date, most studies focused on the coding genes and microRNAs in UPR. Other non-coding RNAs affected by UPR and their roles in UPR have not been systematically studied. Long noncoding RNAs (lncRNAs) are increasingly recognized as powerful epigenetic regulators. In this study, we transcriptomically profiled the lncRNAs and mRNAs from mouse embryonic fibroblasts under ER stress, and identified many differentially expressed lncRNAs and mRNAs...
March 21, 2018: Scientific Reports
John Sidney, Jose Luis Vela, Dave Friedrich, Ravi Kolla, Matthias von Herrath, Johnna D Wesley, Alessandro Sette
BACKGROUND: Type 1 diabetes (T1D) is thought to be an autoimmune disease driven by anti-islet antigen responses and mediated by T-cells. Recent published data suggests that T-cell reactivity to modified peptides, effectively neoantigens, may promote T1D. These findings have given more credence to the concept that T1D may not be solely an error of immune recognition but may be propagated by errors in protein processing or in modifications to endogenous peptides occurring as result of hyperglycemia, endoplasmic reticulum (ER) stress, or general beta cell dysfunction...
March 21, 2018: BMC Immunology
Claudia Cavallini, Chiara Zannini, Elena Olivi, Riccardo Tassinari, Valentina Taglioli, Martina Rossi, Paola Poggi, Alexandros Chatgilialoglu, Giuliana Simonazzi, Francesco Alviano, Laura Bonsi, Carlo Ventura
Human mesenchymal stem cells (hMSCs) are an effective tool in regenerative medicine notably for their intrinsic plentiful paracrine activity rather than differentiating properties. The hMSC secretome includes a wide spectrum of regulatory and trophic factors, encompassing several naked molecules as well as different kinds of extracellular vesicles (EVs). Among EVs, exosomes represent an intriguing population, able to shuttle proteins, transcription factors, and genetic materials, with a relevant role in cell-to-cell communication, modulating biological responses in recipient cells...
January 2018: Cell Transplantation
Jie Meng, Wen-Xiong Wang, Li Li, Guofan Zhang
Lead (Pb) is one of the ubiquitous and toxic elements in aquatic environment. In oysters, gills and digestive glands are the main target organs for Pb-induced toxicity, but there is limited information on the molecular mechanisms underlying its toxicity. The present study investigated the Pb-induced toxicity mechanisms in the Pacific oyster (Crassostrea gigas) based on transcriptome, phenotypic anchoring, and validation of targeted gene expression. Gene ontology and pathway enrichment analyses revealed the differential Pb toxicity mechanisms in the tissues...
March 13, 2018: Aquatic Toxicology
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
Daiqiang Liu, Yaqun Zhou, Yawen Peng, Peng Su, Zheng Li, Qiaoqiao Xu, Ye Tu, Xuebi Tian, Hui Yang, Zhen Wu, Wei Mei, Feng Gao
Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer's disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days...
2018: Frontiers in Molecular Neuroscience
Alex B Addinsall, Craig R Wright, Sof Andrikopoulos, Chris van der Poel, Nicole Stupka
Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins - 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T...
March 20, 2018: Biochemical Journal
Cristhiaan D Ochoa, Ru Feng Wu, Lance S Terada
The endoplasmic reticulum (ER) produces the vast majority of all proteins secreted into the extracellular space, including hormones and cytokines, as well as cell surface receptors and other proteins which interact with the environment. Accordingly, this organelle controls essentially all vital links to a cell's external milieu, responding to systemic metabolic, inflammatory, endocrine, and mechanical stimuli. The central role the ER plays in meeting protein synthetic and quality control requirements in the face of such demands is matched by an extensive and versatile ER stress response signaling network...
March 17, 2018: Molecular Aspects of Medicine
Hai-Cheng Dou, Jun-Yu Chen, Tang-Fei Ran, Wei-Min Jiang
The treatment goal in spinal cord injury (SCI) is to repair neurites and suppress cell apoptosis. Panax quinquefolius saponin (PQS) is the major active ingredient of American ginseng and has been demonstrated to have anti-inflammatory and anti-apoptotic roles in various diseases. However, the potential effect of PQS on the pathological process of acute SCI remains unknown. This work tested the effects of PQS on acute SCI and clarified its potential mechanisms. PQS treatment ameliorated the damage to spinal tissue and improved the functional recovery after SCI...
March 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Judith A Smith
Protein folding in the endoplasmic reticulum (ER) is an essential cell function. To safeguard this process in the face of environmental threats and internal stressors, cells mount an evolutionarily conserved response known as the unfolded protein response (UPR). Invading pathogens induce cellular stress that impacts protein folding, thus the UPR is well situated to sense danger and contribute to immune responses. Cytokines (inflammatory cytokines and interferons) critically mediate host defense against pathogens, but when aberrantly produced, may also drive pathologic inflammation...
2018: Frontiers in Immunology
Liping Luo, Wanxiang Jiang, Hui Liu, Jicheng Bu, Ping Tang, Chongyangzi Du, Zhipeng Xu, Hairong Luo, Bilian Liu, Bo Xiao, Zhiguang Zhou, Feng Liu
The growth receptor binding protein Grb10 is an imprinted gene product and a key negative regulator of the insulin, IGF1 and mTORC1 signaling pathways. Grb10 is highly expressed in mouse fetal liver but almost completely silenced in adult mice, suggesting a potential detrimental role of this protein in adult liver function. Here we show that the grb10 gene could be reactivated in adult mouse liver by acute endoplasmic reticulum stress (ER stress) such as tunicamycin or a short-term high fat diet (HFD) challenge, concurrently with increased unfolded protein response (UPR) and hepatosteatosis...
March 19, 2018: Journal of Molecular Endocrinology
Susanne Smaardijk, Jialin Chen, Sara Kerselaers, Thomas Voets, Jan Eggermont, Peter Vangheluwe
The Secretory Pathway Ca2+ ATPases SPCA1 and SPCA2 transport Ca2+ and Mn2+ into the Golgi and Secretory Pathway. SPCA2 mediates store-independent Ca2+ entry (SICE) via STIM1-independent activation of Orai1, inducing constitutive Ca2+ influx in mammary epithelial cells during lactation. Here, we show that like SPCA2, also the overexpression of the ubiquitous SPCA1 induces cytosolic Ca2+ influx, which is abolished by Orai1 knockdown and occurs independently of STIM1. This process elevates the Ca2+ concentration in the cytosol and in the non-endoplasmic reticulum (ER) stores, pointing to a functional coupling between Orai1 and SPCA1...
March 16, 2018: Biochimica et Biophysica Acta
Hwa Yeon Kim, Ha Na Song, Munkhtugs Davaatseren, Hyun Joo Chang, Hyang Sook Chun
BACKGROUND: It is well known that endoplasmic reticulum (ER) stress plays a huge role in development of metabolic diseases. Specially, ER stress-induced cellular dysfunction has a significant involvement in the pathogenesis of human chronic disorders. This study was designed to study to assess whether an ethanol extract of Coicis Semen (CSE) and coixol induces the ER stress in Chang liver cells. METHODS: Coicis Semen was mixed with 95% ethanol at a ratio of 1:10 (w/v) and freeze dried...
March 20, 2018: BMC Complementary and Alternative Medicine
Jie Lei, Lei Zhao, Yujing Zhang, Yanfeng Wu, Yanbo Liu
BACKGROUND/AIMS: The mechanisms by which high glucose (HG) results in podocyte damage remains unclear. We investigated the potential role of endoplasmic reticulum (ER) stress and mTOR signaling in HG injured podocyte. METHODS: In cultured mouse podocytes, cellular apoptosis was assessed using FITC-Annexin V and propidium iodide staining followed by flow cytometry analysis. Apoptosis-related proteins as well as the ER stress and the mTOR signals were evaluated using immunoblot assay...
March 15, 2018: Cellular Physiology and Biochemistry
Eri Soejima, Tsuyoshi Ohki, Yayoi Kurita, Xiaohong Yuan, Kayo Tanaka, Satomi Kakino, Kento Hara, Hitomi Nakayama, Yuji Tajiri, Kentaro Yamada
AIMS/HYPOTHESIS: The aim of this study was to elucidate the mechanism by which severe hypoglycemia accelerates vascular complications. Furthermore, we assessed the possible protective effect of ketone bodies against the endothelial cell damage caused by glucose deficiency. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured at a glucose level of either 0.56 or 5.6 mmol/L with or without 3-hydroxybutyrate (3-HB) supplementation. Cell viability was assessed with a CCK-8 assay and a lactate dehydrogenase (LDH) release assay...
2018: PloS One
Ritu S Sharma, David J Harrison, Dorothy Kisielewski, Diane M Cassidy, Alison D McNeilly, Jennifer R Gallagher, Shaun V Walsh, Tadashi Honda, Rory J McCrimmon, Albena T Dinkova-Kostova, Michael L J Ashford, John F Dillon, John D Hayes
Background & Aims: Nonalcoholic steatohepatitis (NASH) is associated with oxidative stress. We surmised that pharmacologic activation of NF-E2 p45-related factor 2 (Nrf2) using the acetylenic tricyclic bis(cyano enone) TBE-31 would suppress NASH because Nrf2 is a transcriptional master regulator of intracellular redox homeostasis. Methods: Nrf2 +/+ and Nrf2 -/- C57BL/6 mice were fed a high-fat plus fructose (HFFr) or regular chow diet for 16 weeks or 30 weeks, and then treated for the final 6 weeks, while still being fed the same HFFr or regular chow diets, with either TBE-31 or dimethyl sulfoxide vehicle control...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Marie E Boo, J Craig Garrison, Joseph P Hannon, Kalyssa M Creed, Shiho Goto, Angellyn N Grondin, James M Bothwell
Background: Female patients are more likely to suffer a second anterior cruciate ligament (ACL) injury after ACL reconstruction (ACLR) and return to sport (RTS) compared with healthy female controls. Few studies have examined the energy absorption contribution (EAC) that could lead to this subsequent injury. Hypothesis: The ACLR group would demonstrate an altered EAC between joints (hip, knee, and ankle) but no difference in quadriceps, hip abduction, or hip external rotation (ER) strength at the time of RTS...
March 2018: Orthopaedic Journal of Sports Medicine
Raju Bishwakarma, Wei Zhang, Yu-Li Lin, Yong-Fang Kuo, Victor J Cardenas, Gulshan Sharma
Background: Chronic obstructive pulmonary disease (COPD) is associated with persistent systemic inflammation. Anti-inflammatory therapies have been shown to decrease acute exacerbations of COPD. The antidiabetic medication metformin decreases oxidative stress and inflammation and may benefit patients with COPD. We aimed at investigating the effect of metformin on health care utilizations in patients with coexisting COPD and diabetes mellitus (DM). Methods: We studied 5% Medicare beneficiaries with coexisting COPD and DM prescribed metformin or other antidiabetics during the period 2007-2010...
2018: International Journal of Chronic Obstructive Pulmonary Disease
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