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https://www.readbyqxmd.com/read/28935975/tumor-necrosis-factor-inducible-gene-6-protein-ameliorates-chronic-liver-damage-by-promoting-autophagy-formation-in-mice
#1
Sihyung Wang, Chanbin Lee, Jieun Kim, Jeongeun Hyun, Minso Lim, Hyuk-Jin Cha, Seh-Hoon Oh, Yung Hyun Choi, Youngmi Jung
Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0...
September 22, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28935601/ctenopharyngodon-idella-perk-eif2ak3-decreases-cell-viability-by-phosphorylating-eif2%C3%AE-under-er-stress
#2
Tao Zhang, Dongming Li, Lijuan Wan, Xin Chen, Xiangqin Wang, Bin Zhong, Zhen Wu, Huiling Mao, Chengyu Hu
As an upstream kinase of eIF2α, protein kinase RNA-like ER (endoplasmic reticulum) kinase (PERK) is a type I transmembrane protein located in ER in eukaryotic cells. PERK is mainly composed of two domains, the intracavitary domain for BIP protein combination and the dissociative C-terminal region containing a typical serine/threonine kinase domain which promotes the phosphorylation of eIF2α. In this study, we cloned a PERK (also known as EIF2AK3) gene from grass carp (Ctenopharyngodon idella). The full-length cDNA of grass carp PERK (CiPERK) is 5192 bp including a 176 bp of 5' untranslated region, a 1719 bp of 3' untranslated region and a 3297 bp of the longest open reading frame (ORF) encoding 1098 amino acids...
September 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28923079/endoplasmic-reticulum-stress-cooperates-with-toll-like-receptor-ligation-in-driving-activation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#3
Pawel A Kabala, Chiara Angiolilli, Nataliya Yeremenko, Aleksander M Grabiec, Barbara Giovannone, Desiree Pots, Timothy R Radstake, Dominique Baeten, Kris A Reedquist
BACKGROUND: Endoplasmic reticulum (ER) stress has proinflammatory properties, and transgenic animal studies of rheumatoid arthritis (RA) indicate its relevance in the process of joint destruction. Because currently available studies are focused primarily on myeloid cells, we assessed how ER stress might affect the inflammatory responses of stromal cells in RA. METHODS: ER stress was induced in RA fibroblast-like synoviocytes (FLS), dermal fibroblasts, and macrophages with thapsigargin or tunicamycin alone or in combination with Toll-like receptor (TLR) ligands, and gene expression and messenger RNA (mRNA) stability was measured by quantitative polymerase chain reaction...
September 18, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28904818/nf-%C3%AE%C2%BAb-pathway-link-with-er-stress-induced-autophagy-and-apoptosis-in-cervical-tumor-cells
#4
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28904368/polycystin-1-inhibits-eif2%C3%AE-phosphorylation-and-cell-apoptosis-through-a-pkr-eif2%C3%AE-pathway
#5
Yan Tang, Zuocheng Wang, JungWoo Yang, Wang Zheng, Di Chen, Guanqing Wu, Richard Sandford, Jingfeng Tang, Xing-Zhen Chen
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2 which encodes polycystin-1 (PC1) and polycystin-2, respectively. PC1 was previously shown to slow cell proliferation and inhibit apoptosis but the underlying mechanisms remain elusive or controversial. Here we showed in cultured mammalian cells and Pkd1 knockout mouse kidney epithelial cells that PC1 and its truncation mutant comprising the last five transmembrane segments and the intracellular C-terminus (PC1-5TMC) down-regulate the phosphorylation of protein kinase R (PKR) and its substrate eukaryotic translation initiation factor 2 alpha (eIF2α)...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28885691/fibroblast-growth-factor-2-induces-proliferation-and-distribution-of-g2-m-phase-of-bovine-endometrial-cells-involving-activation-of-pi3k-akt-and-mapk-cell-signaling-and-prevention-of-effects-of-er-stress
#6
Whasun Lim, Hyocheol Bae, Fuller W Bazer, Gwonhwa Song
Fibroblast growth factor 2 (FGF2) is abundantly expressed in conceptuses and endometria during pregnancy in diverse animal models including domestic animals. However, its intracellular mechanism of action has not been reported for bovine endometrial cells. Therefore, the aim of this study was to identify functional roles of FGF2 in bovine endometrial (BEND) cell line which has served as a good model system for investigating regulation of signal transduction following treatment with interferon-tau (IFNT) in vitro...
September 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28883502/activation-of-endoplasmic-reticulum-stress-in-granulosa-cells-from-patients-with-polycystic-ovary-syndrome-contributes-to-ovarian-fibrosis
#7
Nozomi Takahashi, Miyuki Harada, Yasushi Hirota, Emi Nose, Jerilee Mk Azhary, Hiroshi Koike, Chisato Kunitomi, Osamu Yoshino, Gentaro Izumi, Tetsuya Hirata, Kaori Koga, Osamu Wada-Hiraike, R Jeffrey Chang, Shunichi Shimasaki, Tomoyuki Fujii, Yutaka Osuga
Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis. In the present study, we showed that ER stress was activated in granulosa cells of PCOS patients as well as in a well-established PCOS mouse model...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28880013/osimertinib-azd9291-decreases-programmed-death-ligand-1-in-egfr-mutated-non-small-cell-lung-cancer-cells
#8
Xiao-Ming Jiang, Yu-Lian Xu, Mu-Yang Huang, Le-Le Zhang, Min-Xia Su, Xiuping Chen, Jin-Jian Lu
Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has been approved for the treatment of EGFR-mutated non-small cell lung cancer (NSCLC). In NSCLC patients, an EGFR mutation is likely to be correlated with high levels of expression of programmed death ligand-1 (PD-L1). Here, we showed that osimertinib decreased PD-L1 expression in human EGFR mutant NSCLC cells in vitro. Osimertinib (125 nmol/L) markedly suppressed PD-L1 mRNA expression in both NCI-H1975 and HCC827 cells...
September 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28874370/n-acetylglucosamine-1-phosphate-transferase-weca-as-a-validated-drug-target-in-mycobacterium-tuberculosis
#9
Stanislav Huszár, Vinayak Singh, Alica Polčicová, Peter Baráth, María Belén Barrio, Sophie Lagrange, Véronique Leblanc, Carol A Nacy, Valerie Mizrahi, Katarína Mikušová
The mycobacterial phosphoglycosyltransferase, WecA, which initiates arabinogalactan biosynthesis in Mycobacterium tuberculosis, has been proposed as a target of the caprazamycin derivative, CPZEN-45, a preclinical drug candidate for treatment of tuberculosis. In this report, we describe the functional characterization of mycobacterial WecA and confirm the essentiality of its encoding gene in M. tuberculosis by demonstrating that transcriptional silencing of wecA is bactericidal in vitro and in macrophages. Silencing of wecA also conferred hypersensitivity of M...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28868122/allicin-attenuates-tunicamycin-induced-cognitive-deficits-in-rats-via-its-synaptic-plasticity-regulatory-activity
#10
Qiong Xiang, Xian-Hui Li, Bo Yang, Xin-Xing Fang, Jing Jia, Jie Ren, Yu-Chun Dong, Cheng Ou-Yang, Guang-Cheng Wang
OBJECTIVES: To illuminate the functional effects of allicin on rats with cognitive deficits induced by tunicamycin (TM) and the molecular mechanism of this process. MATERIALS AND METHODS: 200-250 g male SD rats were divided into three groups at random: control group (n=12), TM group (5 μl, 50 μM, ICV, n=12), and allicin treatment group (180 mg/kg/d with chow diet, n=12). After 16 weeks of allicin treatment, the learning ability and memory were tested using novel object recognition (NOR) testing on rats with 72 hr TM treatment (5 μl, 50 μM, ICV); meanwhile, the variation of field excitatory postsynaptic potential (fEPSP) in the Schaffer Collateral (SC)-CA1 synapse was detected by extracellular electrophysiological recordings and the morphology of dendritic spine was observed by Golgi staining as well as detecting several synaptic plasticity-related proteins by Western blot...
June 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28845672/proteome-wide-analysis-of-n-glycosylation-stoichiometry-using-swath-technology
#11
Xiangyun Yang, Wang Zhiyuan, Lin Guo, Zheng-Jiang Zhu, Yaoyang Zhang
N-glycosylation is a crucial post-translational modification (PTM) and plays essential roles in biological processes. Several methods have been developed for the relative quantification of N-glycosylation at the proteome scale. However, the proportion of N-glycosylated forms in a total protein population, or the "N-glycosylation stoichiometry," varies greatly among proteins or cellular states and is frequently missing due to the lack of robust technologies. In the present study, we developed a data-independent acquisition (DIA) based strategy that enabled the in-depth measurement of N-glycosylation stoichiometry...
August 28, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28844859/endoplasmic-reticulum-stress-restrains-hepatocyte-growth-factor-expression-in-hepatic-stellate-cells-and-rat-acute-liver-failure-model
#12
Yuting Liu, Xiongxiong Pan, Shu Li, Yue Yu, Jianliang Chen, Jie Yin, Guoqiang Li
The aim of this study was to test whether endoplasmic reticulum (ER) stress suppresses hepatocyte growth factor (HGF) expression in hepatic stellate cells (HSCs) and whether ER stress plays a role in alleviating d-Galactosamine and Lipopolysaccharide (D-GalN/LPS)-induced acute liver failure (ALF) by regulating HGF expression. Rat HSCs line HSC-T6 were treated with the ER stress inducers tunicamycin or thapsigargin, and ER stress inhibitors sodium 4-phenylbutyrate (4-PBA) or salubrinal, respectively. Recombinant lentivirus containing eukaryotic translation initiation factor 2α (eIf2α), named LV-eIf2α-shRNA-GFP was produced to block eIf2α activated by ER stress...
August 24, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28841673/chop-favors-endoplasmic-reticulum-stress-induced-apoptosis-in-hepatocellular-carcinoma-cells-via-inhibition-of-autophagy
#13
Yan Lei, Shuiliang Wang, Bingshuang Ren, Jin Wang, Jin Chen, Jun Lu, Shihuai Zhan, Yunfeng Fu, Lianghu Huang, Jianming Tan
C/EBP-homologous protein (CHOP) is an important component of the endoplasmic reticulum (ER) stress response. We demonstrated the induction of ER stress in response to tunicamycin stimulation, as evidenced by increased expression of chaperone proteins Grp78, Grp94, and enhanced eukaryotic initiation factor 2 subunit 1 (eIF2α) phosphorylation in hepatocellular carcinoma cells. Tunicamycin-induced ER stress resulted in apoptosis and autophagy simultaneously. While inhibition of autophagy mediated by 3-methyladenine pretreatment or direct knockdown of LC3B promoted cell apoptosis, activation of autophagy with rapamycin decreased tunicamycin- induced apoptosis in HCC cells...
2017: PloS One
https://www.readbyqxmd.com/read/28839162/microrna-204-promotes-vascular-endoplasmic-reticulum-stress-and-endothelial-dysfunction-by-targeting-sirtuin1
#14
Modar Kassan, Ajit Vikram, Qiuxia Li, Young-Rae Kim, Santosh Kumar, Mohanad Gabani, Jing Liu, Julia S Jacobs, Kaikobad Irani
Endoplasmic reticulum (ER) stress has been implicated in vascular endothelial dysfunction of obesity, diabetes, and hypertension. MicroRNAs play an important role in regulating ER stress. Here we show that microRNA-204 (miR-204) promotes vascular ER stress and endothelial dysfunction by targeting the Sirtuin1 (Sirt1) lysine deacetylase. Pharmacologic ER stress induced by tunicamycin upregulates miR-204 and downregulates Sirt1 in the vascular wall/endothelium in vivo and in endothelial cells in vitro. Inhibition of miR-204 protects against tunicamycin-induced vascular/endothelial ER stress, associated impairment of endothelium-dependent vasorelaxation, and preserves endothelial Sirt1...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28832690/development-of-a-fluorescent-reporter-system-for-monitoring-er-stress-in-chinese-hamster-ovary-cells-and-its-application-for-therapeutic-protein-production
#15
Gargi Roy, Shu Zhang, Lina Li, Eileen Higham, Herren Wu, Marcello Marelli, Michael A Bowen
Mammalian cell expression systems have become a workhorse for the production of biotherapeutic proteins. As such, there is an ever increasing demand for higher productivity from these expression platforms to reduce manufacturing costs. While great advances have been made in the optimization of culture conditions and cell line selection to improve productivity, protein mis-folding remains a common limitation to high levels of production of therapeutic proteins. Accumulation of mis- and unfolded protein in the endoplasmic reticulum (ER) causes ER stress and initiates the unfolded protein response (UPR) that results in an activation of protein folding machinery, translation attenuation in an effort to proper folding of the newly synthesized peptides or may even lead to apoptosis if the correct folding is not restored...
2017: PloS One
https://www.readbyqxmd.com/read/28822264/trimethylamine-n-oxide-as-a-risk-factor-for-atherosclerosis-induces-stress-in-j774a-1-murine-macrophages
#16
Abbas Mohammadi, Zakaria Vahabzadeh, Soran Jamalzadeh, Tahereh Khalili
PURPOSE: Trimethylamine N-oxide (TMAO) is a biomarker for kidney problems. It has also been introduced as a risk factor for atherosclerosis. The classic risk factors for atherosclerosis trigger cellular and humeral immunoreaction in macrophages through induction of heat shock protein expressions and increased levels of GRP94 and HSP70 are associated with increased atherosclerosis risk. The present study evaluated the possible effect(s) of TMAO on the expression of GRP94 and HSP70 at protein levels...
August 16, 2017: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28811964/pd-l2-expression-in-colorectal-cancer-independent-prognostic-effect-and-targetability-by-deglycosylation
#17
Huanbin Wang, Han Yao, Chushu Li, Lunxi Liang, Yao Zhang, Hubing Shi, Chongzhi Zhou, Yingxuan Chen, Jing-Yuan Fang, Jie Xu
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28801807/hyaluronan-mediated-mononuclear-leukocyte-binding-to-gingival-fibroblasts
#18
Daniel Hagenfeld, Nico T Mutters, Inga Harks, Raphael Koch, Ti-Sun Kim, Peter Prehm
OBJECTIVES: Binding of mononuclear leukocytes to hyaluronan cable structures is a well-known pathomechanism in several chronic inflammatory diseases, but has not yet described for chronic oral inflammations. The aim of this study was to evaluate if and how binding of mononuclear leukocytes to pathologic hyaluronan cable structures can be induced in human gingival fibroblasts. MATERIAL AND METHODS: Experiments were performed with human gingival fibroblasts and peripheral blood mononuclear cells (PBMCs) from three healthy blood donors...
August 12, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28796837/whole-genome-sequence-of-two-rathayibacter-toxicus-strains-reveals-a-tunicamycin-biosynthetic-cluster-similar-to-streptomyces-chartreusis
#19
Aaron J Sechler, Matthew A Tancos, David J Schneider, Jonas G King, Christine M Fennessey, Brenda K Schroeder, Timothy D Murray, Douglas G Luster, William L Schneider, Elizabeth E Rogers
Rathayibacter toxicus is a forage grass associated Gram-positive bacterium of major concern to food safety and agriculture. This species is listed by USDA-APHIS as a plant pathogen select agent because it produces a tunicamycin-like toxin that is lethal to livestock and may be vectored by nematode species native to the U.S. The complete genomes of two strains of R. toxicus, including the type strain FH-79, were sequenced and analyzed in comparison with all available, complete R. toxicus genomes. Genome sizes ranged from 2,343,780 to 2,394,755 nucleotides, with 2079 to 2137 predicted open reading frames; all four strains showed remarkable synteny over nearly the entire genome, with only a small transposed region...
2017: PloS One
https://www.readbyqxmd.com/read/28782832/aav-delivery-of-grp78-bip-promotes-adaptation-of-human-rpe-cell-to-er-stress
#20
Shima Ghaderi, Shahin Ahmadian, Zahra-Soheila Soheili, Hamid Ahmadieh, Shahram Samiei, Samira Kheitan, Ehsan Ranaei Pirmardan
Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration...
August 7, 2017: Journal of Cellular Biochemistry
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