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https://www.readbyqxmd.com/read/28229251/taurine-ameliorated-homocysteine-induced-h9c2-cardiomyocyte-apoptosis-by-modulating-endoplasmic-reticulum-stress
#1
Zhimin Zhang, Lianyou Zhao, Yanfen Zhou, Xuanhao Lu, Zhengqiang Wang, Jipeng Wang, Wei Li
Homocysteine (Hcy)-triggered endoplasmic reticulum (ER) stress-mediated endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury. However, whether ER stress is the molecular mechanism linking Hcy and cardiomyocytes death is unclear. Taurine has been reported to exert cardioprotective effects via various mechanisms. However, whether taurine protects against Hcy-induced cardiomyocyte death by attenuating ER stress is unknown. This study aimed to evaluate the opposite effects of taurine on Hcy-induced cardiomyocyte apoptosis and their underlying mechanisms...
February 22, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28222026/hypoxic-regulation-of-the-expression-of-genes-encoded-estrogen-related-proteins-in-u87-glioma-cells-eff-ect-of-ire1-inhibition
#2
Minchenko Do, Riabovol Oo, Ratushna Oo, Minchenko Oh
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...
January 1, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#3
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192116/prrt2-inhibits-the-proliferation-of-glioma-cells-by-modulating-unfolded-protein-response-pathway
#4
Guanghui Bi, Jingfeng Yan, Shuzhen Sun
Accumulating studies reported mutations in the gene encoding the proline-rich transmembrane protein 2 (PRRT2) to be causative for several paroxysmal neurological disorders, including paroxysmal kinesigenic dyskinesia (PKD), PKD combined with infantile seizures (ICCA), and benign familial infantile seizures (BFIS). However, the impact of PRRT2 in tumorigenesis is not known. Based on a large-scale data analysis, we found that PRRT2 was down-regulated in glioma tumor tissues compared with normal brain tissue. Dysregulation of PRRT2 was not induced by mutation, copy number variation and epigenetic modification, but modulated by microRNA-30a-5p...
February 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28186986/common-cytotoxic-chemotherapeutics-induce-epithelial-mesenchymal-transition-emt-downstream-of-er-stress
#5
Parag P Shah, Tess V Dupre, Leah J Siskind, Levi J Beverly
Endoplasmic reticulum (ER) in eukaryotes is a main organelle involved in a wide variety of functions including calcium storage, lipid biosynthesis, protein folding and protein transport. Disruption of ER homeostasis leads to ER stress and activation of the unfolded protein response (UPR). We and others have previously found that ER stress induces EMT in different cellular systems. Induction of ER stress with chemical modulators of ER homeostasis was sufficient to activate an EMT-like state in all cellular systems tested...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178380/pre-ischemia-melatonin-treatment-alleviated-acute-neuronal-injury-after-ischemic-stroke-by-inhibiting-er-stress-dependent-autophagy-via-perk-and-ire1-signalings
#6
Dayun Feng, Bao Wang, Lei Wang, Neeta Abraham, Kai Tao, Lu Huang, Wei Shi, Yushu Dong, Yan Qu
Melatonin has demonstrated a potential protective effect in central nervous system. Thus, it is interesting to determine whether pre-ischemia melatonin administration could protect against cerebral ischemia/reperfusion (IR) related injury and the underlying molecular mechanisms. In this study, we revealed that IR injury significantly activated endoplasmic reticulum (ER) stress and autophagy in a middle cerebral artery occlusion (MCAO) mouse model. Pre-ischemia melatonin treatment was able to attenuate IR-induced ER stress and autophagy...
February 8, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28178232/synthetic-vulnerabilities-of-mesenchymal-subpopulations-in-pancreatic-cancer
#7
Giannicola Genovese, Alessandro Carugo, James Tepper, Frederick Scott Robinson, Liren Li, Maria Svelto, Luigi Nezi, Denise Corti, Rosalba Minelli, Piergiorgio Pettazzoni, Tony Gutschner, Chia-Chin Wu, Sahil Seth, Kadir Caner Akdemir, Elisabetta Leo, Samirkumar Amin, Marco Dal Molin, Haoqiang Ying, Lawrence N Kwong, Simona Colla, Koichi Takahashi, Papia Ghosh, Virginia Giuliani, Florian Muller, Prasenjit Dey, Shan Jiang, Jill Garvey, Chang-Gong Liu, Jianhua Zhang, Timothy P Heffernan, Carlo Toniatti, Jason B Fleming, Michael G Goggins, Laura D Wood, Alessandro Sgambato, Abbas Agaimy, Anirban Maitra, Charles W M Roberts, Huamin Wang, Andrea Viale, Ronald A DePinho, Giulio F Draetta, Lynda Chin
Malignant neoplasms evolve in response to changes in oncogenic signalling. Cancer cell plasticity in response to evolutionary pressures is fundamental to tumour progression and the development of therapeutic resistance. Here we determine the molecular and cellular mechanisms of cancer cell plasticity in a conditional oncogenic Kras mouse model of pancreatic ductal adenocarcinoma (PDAC), a malignancy that displays considerable phenotypic diversity and morphological heterogeneity. In this model, stochastic extinction of oncogenic Kras signalling and emergence of Kras-independent escaper populations (cells that acquire oncogenic properties) are associated with de-differentiation and aggressive biological behaviour...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28167662/impaired-ire1-expression-and-xbp1-activation-is-a-hallmark-of-gcb-dlbcl-and-contributes-to-tumor-growth
#8
Bojan Bujisic, Aude De Gassart, Rémy Tallant, Olivier Demaria, Léa Zaffalon, Sonia Chelbi, Michel Gilliet, Francesco Bertoni, Fabio Martinon
The endoplasmic reticulum kinase IRE1 and its downstream target XBP1 drive B cell differentiation towards plasma cells and have been shown to contribute to multiple myeloma development; yet little is known on the role of this pathway in Diffuse Large B cell Lymphoma (DLBCL). Here we show that in Germinal Center B cell-like (GCB) DLBCL subtype, IRE1 expression is reduced to a level that prevents XBP1 activation. Gene expression profiles indicated that, in GCB DLBCL cancer samples, expression of IRE1 mRNA was inversely correlated with the levels and activity of the epigenetic repressor, histone methyltransferase EZH2...
February 6, 2017: Blood
https://www.readbyqxmd.com/read/28155228/athop3-a-member-of-the-hop-family-in-arabidopsis-interacts-with-bip-and-plays-a-major-role-in-the-er-stress-response
#9
Nuria Fernández-Bautista, Lourdes Fernández-Calvino, Alfonso Muñoz, M Mar Castellano
HOP is a well-studied family of cytosolic cochaperones. However, the possible role of HOP during the ER stress response and their interactors within the ER were not previously addressed in any eukaryote. We have demonstrated that Arabidopsis HOP3, whose function was not studied before, interacts in vivo with cytosolic HSP90 and HSP70, and, unexpectedly, with BiP, a HSP70 ER-resident protein. Although BiP lacks the domain described in other eukaryotes for HOP-HSP70 binding, it interacts with HOP3 through a noncanonical association to its nucleotide binding domain...
February 2, 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28137856/targeting-ire1-with-small-molecules-counteracts-progression-of-atherosclerosis
#10
Ozlem Tufanli, Pelin Telkoparan Akillilar, Diego Acosta-Alvear, Begum Kocaturk, Umut Inci Onat, Syed Muhammad Hamid, Ismail Çimen, Peter Walter, Christian Weber, Ebru Erbay
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions...
January 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28114319/reduced-insulin-insulin-like-growth-factor-receptor-signaling-mitigates-defective-dendrite-morphogenesis-in-mutants-of-the-er-stress-sensor-ire-1
#11
Yehuda Salzberg, Andrew J Coleman, Kevin Celestrin, Moran Cohen-Berkman, Thomas Biederer, Sivan Henis-Korenblit, Hannes E Bülow
Neurons receive excitatory or sensory inputs through their dendrites, which often branch extensively to form unique neuron-specific structures. How neurons regulate the formation of their particular arbor is only partially understood. In genetic screens using the multidendritic arbor of PVD somatosensory neurons in the nematode Caenorhabditis elegans, we identified a mutation in the ER stress sensor IRE-1/Ire1 (inositol requiring enzyme 1) as crucial for proper PVD dendrite arborization in vivo. We further found that regulation of dendrite growth in cultured rat hippocampal neurons depends on Ire1 function, showing an evolutionarily conserved role for IRE-1/Ire1 in dendrite patterning...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#12
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28093457/functional-analysis-of-the-mammalian-rna-ligase-for-ire1-in-the-unfolded-protein-response
#13
Juthakorn Poothong, Witoon Tirasophon, Randal J Kaufman
The unfolded protein response (UPR) is a conserved signaling pathway activated upon the accumulation of unfolded proteins within the endoplasmic reticulum (ER), termed ER stress. Upon ER stress, HAC1 / XBP1 undergoes exon/intron specific excision by IRE1 to remove an intron and liberate the 5' and 3' exons. In yeast, the 5' and 3' HAC1 exons are subsequently ligated by tRNA ligase (Rlg1p) whereas XBP1 ligation in mammalian cells is catalyzed by a recently identified ligase, RtcB. In this study, the RNA ligase activity of the human RtcB involved in the unconventional splicing of XBP1 / HAC1 mRNA was explored in an rlg1-100 mutant yeast strain...
January 16, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28093214/the-upr-reduces-glucose-metabolism-via-ire1-signaling
#14
Judith M van der Harg, Jessica C van Heest, Fabian N Bangel, Sanne Patiwael, Jan R T van Weering, Wiep Scheper
Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis...
January 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28075361/role-of-ire1%C3%AE-xbp-1-in-cystic-fibrosis-airway-inflammation
#15
REVIEW
Carla M P Ribeiro, Bob A Lubamba
Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes...
January 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28070729/inhibiting-autophagy-with-chloroquine-enhances-the-anti-tumor-effect-of-high-let-carbon-ions-via-er-stress-related-apoptosis
#16
Xiaogang Zheng, Xiaodong Jin, Feifei Li, Xiongxiong Liu, Yan Liu, Fei Ye, Ping Li, Ting Zhao, Qiang Li
Energetic carbon ions (CI) offer great advantages over conventional radiations such as X- or γ-rays in cancer radiotherapy. High linear energy transfer (LET) CI can induce both endoplasmic reticulum (ER) stress and autophagy in tumor cells under certain circumstances. The molecular connection between ER stress and autophagy in tumor exposed to high-LET radiation and how these two pathways influence the therapeutic effect against tumor remain poorly understood. In this work, we studied the impact of autophagy and apoptosis induced by ER stress following high-LET CI radiation on the radiosensitivity of S180 cells both in vitro and in vivo...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28070110/melatonin-suppresses-methamphetamine-triggered-endoplasmic-reticulum-stress-in-c6-cells-glioma-cell-lines
#17
Wanida Tungkum, Pichaya Jumnongprakhon, Chainarong Tocharus, Piyarat Govitrapong, Jiraporn Tocharus
Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28028078/ire1%C3%AE-in-pomc-neurons-is-required-for-thermogenesis-and-glycemia
#18
Ting Yao, Zhuo Deng, Yong Gao, Jia Sun, Xingxing Kong, Yiru Huang, Zhenyan He, Yanchao Xu, Yongsheng Chang, Kai-Jiang Yu, Brianna G Findley, Eric D Berglund, Rui-Tao Wang, Hongbo Guo, Hong Chen, Xu Li, Randal J Kaufman, Jianqun Yan, Tiemin Liu, Kevin W Williams
Whether neuronal inositol-requiring enzyme 1(Ire1) is required for the proper regulation of energy balance and glucose homeostasis is unclear. We found that pro-opiomelanocortin (Pomc)-specific deficiency of Ire1α accelerated diet-induced obesity concomitant with a decrease in energy expenditure. This hypometabolic phenotype included deficits in thermogenic responses to diet and cold exposure as well as 'beiging' of white adipose tissue. We also demonstrate that loss of Ire1α in Pomc neurons impaired whole-body glucose and insulin tolerance as well as hepatic insulin sensitivity...
December 27, 2016: Diabetes
https://www.readbyqxmd.com/read/28017918/effects-of-ketamine-administration-on-mtor-and-reticulum-stress-signaling-pathways-in-the-brain-after-the-infusion-of-rapamycin-into-prefrontal-cortex
#19
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Monique Michels, Mariane Abatti, Beatriz Sonai, Felipe Dal Pizzol, André F Carvalho, João Quevedo
Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC...
December 3, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28004277/tauroursodeoxycholic-bile-acid-arrests-axonal-degeneration-by-inhibiting-the-unfolded-protein-response-in-x-linked-adrenoleukodystrophy
#20
Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme...
February 2017: Acta Neuropathologica
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