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https://www.readbyqxmd.com/read/29769338/the-perk-arm-of-the-unfolded-protein-response-negatively-regulates-transmissible-gastroenteritis-virus-replication-by-suppressing-protein-translation-and-promoting-type-i-ifn-production
#1
Mei Xue, Fang Fu, Yanlong Ma, Xin Zhang, Liang Li, Li Feng, Pinghuang Liu
Coronavirus replication is closely associated with the endoplasmic reticulum (ER), the primary cellular organelle for protein synthesis, folding, and modification. ER stress is a common consequence in coronavirus-infected cells. However, how the virus-induced ER stress influences coronavirus replication and pathogenesis remains controversial. Here, we demonstrated that infection with the alphacoronavirus transmissible gastroenteritis virus (TGEV) induced ER stress and triggered the unfolded protein response (UPR) in vitro and in vivo , and ER stress negatively regulated TGEV replication in vitro Although TGEV infection activated all three UPR pathways (ATF6, IRE1, and PERK), the virus-triggered UPR suppressed TGEV replication in both ST and IPEC-J2 cells primarily through activation of the PERK-eIF2α axis, as shown by functional studies with overexpression, siRNA, or specific chemical inhibitors...
May 16, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29768040/myristate-induced-endoplasmic-reticulum-stress-requires-ceramide-synthases-5-6-and-generation-of-c14-ceramide-in-intestinal-epithelial-cells
#2
Songhwa Choi, Justin M Snider, Nicole Olakkengil, Johana M Lambert, Andrea K Anderson, Jessica S Ross-Evans, L Ashley Cowart, Ashley J Snider
Saturated fatty acids (SFAs) have been shown to induce endoplasmic reticulum (ER) stress and chronic inflammatory responses, as well as alter sphingolipid metabolism. Disruptions in ER stress and sphingolipid metabolism have also been implicated in intestinal inflammation. Therefore, to elucidate the roles of SFAs in ER stress and inflammation in intestinal epithelial cells, we examined myristate (C14:0) and palmitate (C16:0). Myristate, but not palmitate, induced ER stress signaling, including activation of inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP1) signaling...
May 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29764990/ire1%C3%AE-prevents-hepatic-steatosis-by-processing-and-promoting-the-degradation-of-select-micrornas
#3
Jie-Mei Wang, Yining Qiu, Zhao Yang, Hyunbae Kim, Qingwen Qian, Qinghua Sun, Chunbin Zhang, Lei Yin, Deyu Fang, Sung Hong Back, Randal J Kaufman, Ling Yang, Kezhong Zhang
Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization...
May 15, 2018: Science Signaling
https://www.readbyqxmd.com/read/29760094/salicylic-acid-independent-role-of-npr1-is-required-for-protection-from-proteotoxic-stress-in-the-plant-endoplasmic-reticulum
#4
Ya-Shiuan Lai, Luciana Renna, John Yarema, Cristina Ruberti, Sheng Yang He, Federica Brandizzi
The unfolded protein response (UPR) is an ancient signaling pathway designed to protect cells from the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER). Because misregulation of the UPR is potentially lethal, a stringent surveillance signaling system must be in place to modulate the UPR. The major signaling arms of the plant UPR have been discovered and rely on the transcriptional activity of the transcription factors bZIP60 and bZIP28 and on the kinase and ribonuclease activity of IRE1, which splices mRNA to activate bZIP60...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29747876/the-unknown-face-of-ire1%C3%AE-beyond-er-stress
#5
REVIEW
Ahmad Abdullah, Palaniyandi Ravanan
IRE1α (Inositol Requiring kinase Enzyme 1 alpha), a transmembrane protein localized to the endoplasmic reticulum (ER) is a master regulator of the unfolded protein response (UPR) pathway. The fate determining steps during ER stress-induced apoptosis are greatly attributed to IRE1α's endoribonuclease and kinase activities. Apart from its role as a chief executioner in ER stress, recent studies have shown that upon activation in the presence or absence of ER stress, IRE1α executes multiple cellular processes such as differentiation, immune response, progression and repression of the cell cycle...
May 4, 2018: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29743975/hypothyroidism-causes-endoplasmic-reticulum-stress-in-adult-rat-hippocampus-a-mechanism-associated-with-hippocampal-damage
#6
Alejandra Paola Torres-Manzo, Margarita Franco-Colín, Vanessa Blas-Valdivia, Marisol Pineda-Reynoso, Edgar Cano-Europa
Thyroid hormones (TH) are essential for hippocampal neuronal viability in adulthood, and their deficiency causes hypothyroidism, which is related to oxidative stress events and neuronal damage. Also, it has been hypothesized that hypothyroidism causes a glucose deprivation in the neuron. This study is aimed at evaluating the temporal participation of the endoplasmic reticulum stress (ERE) in hippocampal neurons of adult hypothyroid rats and its association with the oxidative stress events. Adult Wistar male rats were divided into euthyroid and hypothyroid groups...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29740349/severe-burn-induced-intestinal-epithelial-barrier-dysfunction-is-associated-with-endoplasmic-reticulum-stress-and-autophagy-in-mice
#7
Yalan Huang, Yanhai Feng, Yu Wang, Pei Wang, Fengjun Wang, Hui Ren
The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29732320/activation-of-host-ire1%C3%AE-dependent-signaling-axis-contributes-the-intracellular-parasitism-of-brucella-melitensis
#8
Aseem Pandey, Furong Lin, Ana L Cabello, Luciana F da Costa, Xuehuan Feng, Hui-Qiang Feng, Ming-Zhe Zhang, Takao Iwawaki, Allison Rice-Ficht, Thomas A Ficht, Paul de Figueiredo, Qing-Ming Qin
Brucella spp. are intracellular vacuolar pathogens that causes brucellosis, a worldwide zoonosis of profound importance. We previously demonstrated that the activity of host unfolded protein response (UPR) sensor IRE1α (inositol-requiring enzyme 1) and ER-associated autophagy confer susceptibility to Brucella melitensis and Brucella abortus intracellular replication. However, the mechanism by which host IRE1α regulates the pathogen intracellular lifestyle remains elusive. In this study, by employing a diverse array of molecular approaches, including biochemical analyses, fluorescence microscopy imaging, and infection assays using primary cells derived from Ern1 (encoding IRE1) conditional knockout mice, we address this gap in our understanding by demonstrating that a novel IRE1α to ULK1, an important component for autophagy initiation, signaling axis confers susceptibility to Brucella intracellular parasitism...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29723631/paraptosis-in-human-glioblastoma-cell-line-induced-by-curcumin
#9
Monika Garrido-Armas, Juan Carlos Corona, Maria Luisa Escobar, Leda Torres, Francisco Ordóñez-Romero, Abrahan Hernández-Hernández, Francisco Arenas-Huertero
Curcumin is a polyphenol compound extracted from Curcuma longa plant, is a molecule with pleiotropic effects that suppresses transformation, proliferation and metastasis of malignant tumors. Curcumin can cause different kinds of cell death depending of its concentration on the exposed cell type. Here we show that exposure of the glioblastoma cell line A172 to curcumin at 50 μM, the IC50, causes morphological changes characteristic of paraptosis cell-death. Vesicles derived from the ER and low membrane potential of the mitochondria were constantly found in the exposed cells...
April 30, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29720183/disrupted-sphingolipid-metabolism-following-acute-clozapine-and-olanzapine-administration
#10
Katrina Weston-Green, Ilijana Babic, Michael de Santis, Bo Pan, Magdalene K Montgomery, Todd Mitchell, Xu-Feng Huang, Jessica Nealon
BACKGROUND: Second generation antipsychotics (SGAs) induce glucometabolic side-effects, such as hyperglycemia and insulin resistance, which pose a therapeutic challenge for mental illness. Sphingolipids play a role in glycaemic balance and insulin resistance. Endoplasmic reticulum (ER) stress contributes to impaired insulin signalling and whole-body glucose intolerance. Diabetogenic SGA effects on ER stress and sphingolipids, such as ceramide and sphingomyelin, in peripheral metabolic tissues are unknown...
May 2, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29702235/inositol-requiring-enzyme-1-involved-in-regulating-hemocyte-apoptosis-upon-heat-stress-in-patinopecten-yessoensis
#11
Yichen Wu, Chuanyan Yang, Dongyang Liu, Mengmeng Lu, Guangxia Lu, Jiejie Sun, Yuting Huang, Chao Liu, Lingling Wang, Linsheng Song
The inositol-requiring enzyme 1 (IRE1), one of the primary endoplasmic reticulum (ER) transmembrane receptor proteins, is involved in regulating unfolded protein response (UPR) signaling pathway and plays an import role in maintaining cell homeostasis. In the present study, an IRE1 homologue was identified from Patinopecten yessoensis (designated as PyIRE1). The cDNA of PyIRE1 was of 3314 bp with a 2646 bp open reading frame (ORF) of IRE1 encoding a polypeptide of 881 amino acids. There were a signal peptide, four pyrrolo-quinoline quinine (PPQ) domains, a transmembrane helix region, a Serine/Threonine protein kinases domain (S_TKc) and a protein kinases or N-glycanases containing protein domain (PUG) in the deduced amino acid sequence of PyIRE1...
April 24, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29695649/stf-083010-an-inhibitor-of-xbp1-splicing-attenuates-acute-renal-failure-in-rats-by-suppressing-endoplasmic-reticulum-stress-induced-apoptosis-and-inflammation
#12
Lei Liu, Lu Xu, Shaoqing Zhang, Dong Wang, Guoxia Dong, Hanwen Chen, Xinjian Li, Chi Shu, Rong Wang
Endoplasmic reticulum (ER) stress is one of the driving forces of ischemia/reperfusion (IR)-induced acute renal failure (ARF). STF-083010, an inhibitor of the endonuclease activity of inositol-requiring enzyme-1 (IRE1), has the potential to block the initiation of a prolonged unfolded protein response (UPR) that is stimulated by ER stress and alleviates the impairments due to ER stress. In the current study, it was hypothesized that STF-083010 was capable of ameliorating ER stress-related damages in IR-induced ARF...
April 25, 2018: Experimental Animals
https://www.readbyqxmd.com/read/29684344/er-stress-attenuation-by-aloe-derived-polysaccharides-in-the-protection-of-pancreatic-%C3%AE-cells-from-free-fatty-acid-induced-lipotoxicity
#13
Kisoo Kim, Min Hwa Chung, Soyoung Park, Jimin Cha, Jin Hong Baek, Shin-Young Lee, Sang-Yun Choi
Insulin resistance, a pathophysiology of type 2 diabetes, is associated with obesity. Lipotoxicity in obesity leads to the dysfunction and death of pancreatic β-cells and inadequate insulin production, thereby aggravating type 2 diabetes. The present study was conducted to determine the effect of Aloe vera polysaccharides (APs) as an anti-hyperglycemic agent and their mechanisms of action. Gel polysaccharides from Aloe extracts were separated using ultrafiltration devices with molecular weight-cutoff membranes, and the protective effect of APs on pancreatic β-cells in response to free fatty acids (FFAs) was determined...
June 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29678641/liver-directed-microrna-7a-depletion-induces-nonalcoholic-fatty-liver-disease-by-stabilizing-yy1-mediated-lipogenic-pathways-in-zebrafish
#14
Chi-Yu Lai, Chiu-Ya Lin, Chia-Chun Hsu, Kun-Yun Yeh, Guor Mour Her
Nonalcoholic fatty liver disease (NAFLD) has been associated with the function and changes in expression levels of microRNAs (miRs). MiR-7 has been proven to play an important role in many cellular processes; however, its functions in the context of liver lipogenesis remain unknown. We applied the microRNA-sponge (miR-SP) technology and generated transgenic miR-7a-SP models (hC7aSP and bC7aSP), which disrupted the activities of hepatic miR-7a and induced the early onset of NAFLD and nonalcoholic steatohepatitis (NASH) in zebrafish...
April 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29676829/er-stress-mediated-autophagy-protects-against-%C3%AE-%C3%AE-dimethylacrylshikonin-induced-apoptosis-in-lung-adenocarcinoma-cells
#15
Haibing Wang, Gaochenxi Zhang
β,β-Dimethylacrylshikonin (DMAS) is an anti-cancer compound extracted from the roots of Lithospermum erythrorhizon. This study aims to investigate the effects of DMAS on human lung adenocarcinoma cells in vitro and explored the mechanisms of its anti-cancer action. We demonstrated that DMAS markedly inhibited cell viability in a dose- and time-dependent manner, and induced apoptosis as well as autophagy in human lung adenocarcinoma cells. Furthermore, we found that DMAS stimulated endoplasmic reticulum (ER) stress and mediated autophagy via the PERK-eIF2α-ATF4-CHOP and IRE1-TRAF2-JNK axises of the unfolded protein response (UPR) in human lung adenocarcinoma cells...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29674750/publisher-correction-akt-mtor-signaling-modulates-the-dynamics-of-ire1-rnase-activity-by-regulating-er-mitochondria-contacts
#16
Miguel Sanchez-Alvarez, Miguel Angel Del Pozo, Chris Bakal
A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
April 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29663887/the-role-of-ire1-signaling-in-central-nervous-system-diseases
#17
Haibo Ni, Qin Rui, Di Li, Rong Gao, Gang Chen
The accumulation of misfolded or unfolded proteins in endoplasmic reticulum (ER) lumen results in activation of an adaptive stress process called the unfolded protein response (UPR). As the most conserved signaling branch of the UPR, Inositol-requiring enzyme 1 (IRE1) possesses both Ser/Thr kinase and RNase activities that operates as a major stress sensor, mediating both adaptive and pro-apoptotic pathways under ER stress. Over the last three decades, a mounting body of evidence has shown that IRE1 signaling dysfunction is involved in pathology of various neurological disorders...
April 15, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29616060/arabidopsis-gaap1-and-gaap3-modulate-the-unfolded-protein-response-and-the-onset-of-cell-death-in-response-to-er-stress
#18
Kun Guo, Wei Wang, Weiwei Fan, Zhiying Wang, Manli Zhu, Xiaohan Tang, Wenting Wu, Xue Yang, Xinghua Shao, Yue Sun, Wei Zhang, Xiaofang Li
The function of human Golgi antiapoptotic proteins (GAAPs) resembles that of BAX inhibitor-1, with apoptosis inhibition triggered by intrinsic and extrinsic stimuli. However, little is known about the function of GAAP-related proteins in plants. Here, we studied Arabidopsis GAAP1 and GAAP3 and found that they were localized on the cellular membrane, including the endoplasmic reticulum (ER) membrane. The function of GAAP1/GAAP3 in ER-stress response was tested, and results showed that single or double mutation in GAAP1 and GAAP3 reduced plant survival and enhanced cell death under ER stress...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29594345/ubc7-ube2g2-ortholog-in-entamoeba-histolytica-connection-with-the-plasma-membrane-and-phagocytosis
#19
Rinki Kumari, Preeti Gupta, Swati Tiwari
Endoplasmic reticulum (ER)-associated degradation (ERAD) and unfolded protein response (UPR) pathways are important for quality and quantity control of membrane and secretory proteins. We have identified orthologs of ER-associated ubiquitin conjugating enzymes (E2s) Ubc6/Ube2j2 and Ubc7/Ube2g2, ubiquitin ligases (E3) Hrd1 and GP78/AMFR, and sensor of UPR, Ire1 in E. histolytica that show conservation of important features of these proteins. Biochemical characterization of the ortholog of ERAD E2, Ubc7/Ube2g2 (termed as EhUbc7), was carried out...
March 28, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29594285/paeoniflorin-prevents-endoplasmic-reticulum-stress-associated-inflammation-in-lipopolysaccharide-stimulated-human-umbilical-vein-endothelial-cells-via-the-ire1%C3%AE-nf-%C3%AE%C2%BAb-signaling-pathway
#20
Juan Chen, Minghua Zhang, Maomao Zhu, Junfei Gu, Jie Song, Li Cui, Dan Liu, Qing Ning, Xiaobin Jia, Liang Feng
Endoplasmic reticulum (ER) stress-associated inflammation is a critical molecular mechanism involved in the pathogenesis of endothelial dysfunction (ED). Hence, strategies for alleviating ER stress-induced inflammation may be essential for the prevention of cardiovascular diseases. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora Pallas is known for its functional properties against vascular inflammation. However, to date, PF-mediated protection against ER stress-dependent inflammation has not been identified...
April 25, 2018: Food & Function
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