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https://www.readbyqxmd.com/read/27897229/global-gene-regulation-during-activation-of-immunoglobulin-class-switching-in-human-b-cells
#1
Youming Zhang, David J Fear, Saffron A G Willis-Owen, William O Cookson, Miriam F Moffatt
Immunoglobulin class switch recombination (CSR) to IgE is a tightly regulated process central to atopic disease. To profile the B-cell transcriptional responses underlying the activation of the germinal centre activities leading to the generation of IgE, naïve human B-cells were stimulated with IL-4 and anti-CD40. Gene expression and alternative splicing were profiled over 12 days using the Affymetrix Human Exon 1.0 ST Array. A total of 1,399 genes, forming 13 temporal profiles were differentially expressed...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895727/deficiency-of-sumo-specific-protease-1-induces-arsenic-trioxide-mediated-apoptosis-by-regulating-xbp1-activity-in-human-acute-promyelocytic-leukemia
#2
Fei-Fei Wang, Ming-Zhu Liu, Yi Sui, Qing Cao, Bo Yan, Mei-Ling Jin, Xi Mo
Small ubiquitin-like modifier (SUMO)/sentrin-specific protease 1 (SENP1), a member of the SENP family, is highly expressed in several neoplastic tissues. However, the effect of SENP1 in acute promyelocytic leukemia (APL) has not been elucidated. In the present study, it was observed that SENP1 deficiency had no effect on the spontaneous apoptosis or differentiation of NB4 cells. Arsenic trioxide (As2O3) could induce the upregulation of endoplasmic reticulum (ER) stress, resulting in the apoptosis of NB4 cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27863885/cell-type-specific-variation-in-the-induction-of-er-stress-and-downstream-events-in-chikungunya-virus-infection
#3
Sarawut Khongwichit, Nitwara Wikan, Bizunesh Abere, Chutima Thepparit, Atichat Kuadkitkan, Sukathida Ubol, Duncan R Smith
Over the last decade infections with the mosquito transmitted chikungunya virus (CHIKV) have become a major worldwide concern, and considerable efforts have been made in understanding the interaction of this virus with the host cell machinery. Studies have documented the induction of the unfolded protein response (UPR), as well as the induction of apoptosis and autophagy in response to CHIKV infection. This study comparatively analysed these three processes in two cell lines, Hela and HepG2. Infection of Hela cells was characterized by activation of the PERK/eIF2α branch of the UPR, the induction of autophagy and early apoptosis, while infection of HepG2 cells was characterized by activation of the IRE/XBP1 branch of the UPR, limited or no activation of autophagy and comparatively later apoptosis...
November 15, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27853103/endoplasmic-reticulum-stress-is-involved-in-2-4-dichlorophenol-induced-hepatotoxicity
#4
Jianbo Fu, Xiaoning Zhang, Peng Chen, Yingmei Zhang
2,4-Dichlorophenol (2,4-DCP) is an environmental pollutant exhibiting a wide spectrum of toxic effects. We investigated the toxic effects and potential mechanisms underlying 2,4-DCP-induced hepatotoxicity. In vitro, 2,4-DCP caused hepatotoxicity manifested by a decrease in cell viability and inhibition of colony formation. Bip and CHOP expression was up-regulated at the mRNA and protein levels. Moreover, 2,4-DCP induced eIF2α phosphorylation and Xbp1 mRNA splicing, indicating that endoplasmic reticulum (ER) stress was activated after exposure of HL7702 cells to 2,4-DCP for 12 hr...
2016: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/27846758/ankylosing-spondylitis-m-csf-derived-macrophages-are-undergoing-unfolded-protein-response-upr-and-express-higher-levels-of-interleukin-23
#5
Alireza Rezaiemanesh, Mahdi Mahmoudi, Ali Akbar Amirzargar, Mahdi Vojdanian, Ahmad Reza Jamshidi, Mohammad Hossein Nicknam
OBJECTIVE: Interleukin (IL)-23/IL-17 pathway involves in the pathogenesis of ankylosing spondylitis (AS). The exact mechanism implicated in overexpression of IL-23 and activation of the IL-23/IL-17 axis is not clear. The aim of the study was to clarify whether macrophages of AS patients undergo unfolded protein response (UPR) and secret increased IL-23. METHODS: Peripheral blood monocyte isolated from 10 HLA-B27(+) patients and 5 HLA-B27(+) normal subjects were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days...
November 16, 2016: Modern Rheumatology
https://www.readbyqxmd.com/read/27826097/oxidative-stress-drives-cd8-t-cells-skin-trafficking-in-vitiligo-via-cxcl16-upregulation-by-activating-the-unfolded-protein-response-in-keratinocytes
#6
Shuli Li, Guannan Zhu, Yuqi Yang, Zhe Jian, Sen Guo, Wei Dai, Qiong Shi, Rui Ge, Jingjing Ma, Ling Liu, Kai Li, Qi Luan, Gang Wang, Tianwen Gao, Chunying Li
BACKGROUND: In vitiligo, elevated reactive oxygen species (ROS) have been proven as a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment e.g. keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and recently found to mediate homing of CD8(+)T cells in human skin. OBJECTIVE: To explicate the effect of oxidative stress on human keratinocyte and its capacity to drive CD8(+)T cell trafficking via CXCL16 regulation...
November 5, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27824316/nickel-chloride-nicl2-in-hepatic-toxicity-apoptosis-g2-m-cell-cycle-arrest-and-inflammatory-response
#7
Hongrui Guo, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Xun Wang, Ling Zhao, Kejie Chen, Jie Deng
Up to now, the precise mechanism of Ni toxicology is still indistinct. Our aim was to test the apoptosis, cell cycle arrest and inflammatory response mechanism induced by NiCl2 in the liver of broiler chickens. NiCl2 significantly increased hepatic apoptosis. NiCl2 activated mitochondria-mediated apoptotic pathway by decreasing Bcl-2, Bcl-xL, Mcl-1, and increasing Bax, Bak, caspase-3, caspase-9 and PARP mRNA expression. In the Fas-mediated apoptotic pathway, mRNA expression levels of Fas, FasL, caspase-8 were increased...
November 5, 2016: Aging
https://www.readbyqxmd.com/read/27783936/intestinal-ire1-is-required-for-increased-triglyceride-metabolism-and-longer-lifespan-under-dietary-restriction
#8
Nuno Miguel Luis, Lifen Wang, Mauricio Ortega, Hansong Deng, Subhash D Katewa, Patrick Wai-Lun Li, Jason Karpac, Heinrich Jasper, Pankaj Kapahi
Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27765486/tauroursodeoxycholic-acid-improves-pre-implantation-development-of-porcine-scnt-embryo-by-endoplasmic-reticulum-stress-inhibition
#9
Tao Lin, Jae Eun Lee, Reza K Oqani, So Yeon Kim, Eun Seok Cho, Yong Dae Jeong, Jun Jong Baek, Dong Il Jin
The aim of this study is to investigate whether endoplasmic reticulum (ER) stress attenuation could improve porcine somatic cell nuclear transfer (SCNT) embryo developmental competence. We treated porcine SCNT embryos with TUDCA (tauroursodeoxycholic acid, an inhibitor of ER stress) and/or TM (tunicamycin, an ER stress inducer), and examined embryonic developmental potential, embryo quality, the levels of ER stress markers (XBP1 protein and mRNA) and apoptosis-related-genes (BAX and BCL2 mRNA). Immunostaining detected X-box-binding protein (XBP1), a key gene regulator during ER stress, at all stages of SCNT embryo development...
December 2016: Reproductive Biology
https://www.readbyqxmd.com/read/27725908/xbp1-induces-mmp-9-expression-to-promote-proliferation-and-invasion-in-human-esophageal-squamous-cell-carcinoma
#10
Tian Xia, Song Tong, Kai Fan, Wei Zhai, Bin Fang, Si-Hua Wang, Jian-Jun Wang
X-box binding protein 1 (XBP1) was found to be overexpressed in glioma and breast cancers, suggesting that XBP1 might act as a potent oncogenic protein. However, the clinical significance and biological role of XBP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we report that XBP1 is markedly overexpressed in ESCC cell lines and clinical samples. XBP1 overexpression was significantly correlated with ESCC tumor stage, lymph node metastasis and poor outcome. A functional study demonstrated that XBP1 promoted cell growth and cell invasion both in vitro and in vivo...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27713477/antiestrogen-resistant-cell-lines-expressing-estrogen-receptor-%C3%AE-mutations-upregulate-the-unfolded-protein-response-and-are-killed-by-bhpi
#11
Chengjian Mao, Mara Livezey, Ji Eun Kim, David J Shapiro
Outgrowth of metastases expressing ERα mutations Y537S and D538G is common after endocrine therapy for estrogen receptor α (ERα) positive breast cancer. The effect of replacing wild type ERα in breast cancer cells with these mutations was unclear. We used the CRISPR-Cas9 genome editing system and homology directed repair to isolate and characterize 14 T47D cell lines in which ERαY537S or ERαD538G replace one or both wild-type ERα genes. In 2-dimensional, and in quantitative anchorage-independent 3-dimensional cell culture, ERαY537S and ERαD538G cells exhibited estrogen-independent growth...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27701635/the-role-of-ire-xbp1-pathway-in-regulation-of-retinal-pigment-epithelium-tight-junctions
#12
Jacey H Ma, Joshua J Wang, Junhua Li, Bruce A Pfeffer, Yiming Zhong, Sarah X Zhang
Purpose: The retinal pigment epithelium (RPE) tight junctions play a pivotal role in maintaining the homeostatic environment of the neural retina. Herein, we investigated the role of X-box binding protein 1 (XBP1), an endoplasmic reticulum (ER) stress-responsive transcription factor, in regulation of RPE tight junctions. Methods: Human RPE cell line (ARPE-19) and primary primate RPE cells were used for in vitro experiments and RPE-specific XBP1 knockout (KO) mice were used for in vivo study...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27693527/effect-of-hfd-stz-on-expression-of-genes-involved-in-lipid-cholesterol-and-glucose-metabolism-in-rats
#13
Luisa Pozzo, Andrea Vornoli, Ilaria Coppola, Clara Maria Della Croce, Lucia Giorgetti, Pier Giovanni Gervasi, Vincenzo Longo
AIMS: The aim of the study was to evaluate lipid, cholesterol and glucose metabolism in a novel rat model of non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: Rats (Wistar) were fed high fat/cholesterol diet (HFD) and a single low dose (35mg/kg) of streptozotocin (STZ). Collagen and glycogen content, oxidative stress and glucokinase activity were measured using biochemical assays. Other metabolic pathway were assessed by qRT-PCR. KEY FINDINGS: HFD/STZ treated rats, compared to control ones, showed an increase in expression of biomarkers of inflammation (TNFα, IL6), fibrosis (TGFβ), mitochondrial stress (UCP2) and oxidative stress (GSH and carbonylated proteins) but not of ER stress (CHOP, XBP1)...
September 28, 2016: Life Sciences
https://www.readbyqxmd.com/read/27689765/increased-lipogenesis-in-spite-of-upregulated-hepatic-ampk-in-human-nonalcoholic-fatty-liver
#14
Christian von Loeffelholz, Stephanie Döcke, Johan F Lock, Steffi Lieske, Paul Horn, Jennifer Kriebel, Simone Wahl, Paula Singmann, Tonia de Las Heras Gala, Harald Grallert, Nathaniel Raschzok, Igor M Sauer, Regine Heller, Gerhard Jahreis, Ralf A Claus, Michael Bauer, Martin Stockmann, Andreas L Birkenfeld, Andreas F H Pfeiffer
BACKGROUND & AIMS: Molecular adaptations in human nonalcoholic fatty liver disease (NAFLD) are incompletely understood. This study investigated main gene categories related to hepatic de novo lipogenesis (DNL) and lipid oxidation capacity. METHODS: Liver specimens of 48 subjects were histologically classified according to steatosis severity. In depth analyses were performed using real-time polymerase chain reaction (RT-PCR), immunoblotting and immunohistochemistry...
September 30, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27664540/molecular-cloning-and-characterization-of-unfolded-protein-response-genes-from-large-yellow-croaker-larimichthys-crocea-and-their-expression-in-response-to-dietary-fatty-acids
#15
Kai Liao, Jing Yan, Songlin Li, Tianjiao Wang, Wei Xu, Kangsen Mai, Qinghui Ai
The unfolded protein response (UPR) is a mechanism to cope with perturbed endoplasmic reticulum (ER) functions or accumulation of unfolded protein in the ER in eukaryotic cells. Furthermore, the UPR also participates in a number of physiological and pathological processes, such as nutrient sensing, lipid synthesis, and inflammatory response. In this study, four UPR-related genes (GRP78/BiP, ATF6α, XBP1 and CHO) were isolated characterized from large yellow croaker (Larimichthys crocea), and their expression in response to dietary lipid sources (various fatty acids) such as fish oil (FO), palmic acid (PA), olive oil (OO), sunflower oil (SO), and perilla oil (PO), were examined following feeding...
September 21, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27660012/gu-ben-fang-xiao-decoction-attenuates-sustained-airway-inflammation-by-suppressing-er-stress-response-in-a-murine-asthma-remission-model-of-respiratory-syncytial-virus-infection
#16
Yuan Lu, Jian-Ya Xu, Xiao-Hua Zhang, Xia Zhao
ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, asthma has increased dramatically in prevalence with a considerable economic burden all over the world. Long-term remission should be regarded as the promising and meaningful therapeutic goal in asthma management. However, the precise definition criteria and rational therapies for asthma remission have not been well-established. In academia, there is a consensus that even in those who develop asymptomatic remission of asthma, persistent airway inflammation is ubiquitous...
November 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27644325/mist1-links-secretion-and-stress-as-both-target-and-regulator-of-the-upr
#17
David A Hess, Katherine M Strelau, Anju Karki, Mei Jiang, Ana C Azevedo-Pouly, Ann-Hwee Lee, Tye G Deering, Chinh Q Hoang, Raymond J MacDonald, Stephen F Konieczny
Transcriptional networks that govern secretory cell specialization, including instructing cells to develop a unique cytoarchitecture, amass extensive protein synthesis machinery, and be embodied to respond to endoplasmic reticulum (ER) stress, remain largely uncharacterized. In this study, we discovered that the secretory cell transcription factor MIST1 (Bhlha15), previously shown to be essential for cytoskeletal organization and secretory activity, also functions as a potent ER stress-inducible transcriptional regulator...
September 19, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27638906/the-unfolded-protein-response-controls-er-stress-induced-apoptosis-of-lung-epithelial-cells-through-angiotensin-generation
#18
Hang Nguyen, Bruce D Uhal
Recent work from this laboratory showed that endoplasmic reticulum (ER) stress-induced apoptosis of alveolar epithelial cells (AECs) is regulated by the autocrine angiotensin (ANG)II/ANG1-7 system. The proteasome inhibitor MG132 or surfactant protein C (SP-C) BRICHOS domain mutation G100S induced apoptosis in human AECs by activating the proapoptotic cathepsin D and reducing antiapoptotic angiotensin converting enzyme-2 (ACE-2). This study tested the hypothesis that ER stress-induced apoptosis of human AECs might be mediated by influence of the unfolded protein response (UPR) on the autocrine ANGII/ANG1-7 system...
November 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27635239/recent-advances-in-understanding-vitiligo
#19
REVIEW
Prashiela Manga, Nada Elbuluk, Seth J Orlow
Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation...
2016: F1000Research
https://www.readbyqxmd.com/read/27634301/identification-of-doxorubicin-as-an-inhibitor-of-the-ire1%C3%AE-xbp1-axis-of-the-unfolded-protein-response
#20
Dadi Jiang, Connor Lynch, Bruno C Medeiros, Michaela Liedtke, Rakesh Bam, Arvin B Tam, Zhifen Yang, Muthuraman Alagappan, Parveen Abidi, Quynh-Thu Le, Amato J Giaccia, Nicholas C Denko, Maho Niwa, Albert C Koong
Activation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through an in silico drug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as an in vitro and in vivo inhibitor of XBP1 activation, a previously unknown activity for this widely utilized cancer chemotherapeutic drug. Through a series of mechanistic and phenotypic studies, we showed that this novel activity of doxorubicin was not due to inhibition of topoisomerase II (Topo II)...
2016: Scientific Reports
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