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https://www.readbyqxmd.com/read/28303141/the-function-of-fk506-binding-protein-13-in-protein-quality-control-protects-plasma-cells-from-endoplasmic-reticulum-stress-associated-apoptosis
#1
Mini Jeong, Eunkyeong Jang, Suk San Choi, Changhoon Ji, Kyungho Lee, Jeehee Youn
Plasma cells (PCs) are exposed to intense endoplasmic reticulum (ER) stress imposed by enormous rates of immunoglobulin (Ig) synthesis and secretion. Therefore, protein homeostasis is crucial for the survival of PCs, but its molecular mechanism remains largely unknown. Here, we found marked overexpression of FK506-binding protein 13 (FKBP13) in long-lived PCs from autoimmune mice and investigated its function using a plasmacytoma cell line secreting IgA. FKBP13 expression was induced largely in the lumen of ER in response to treatment with an ER stressor tunicamycin or overexpression of an adaptive unfolded protein response (UPR) protein X-box binding protein 1 (XBP1)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28286226/microrna-297-promotes-cardiomyocyte-hypertrophy-via-targeting-sigma-1-receptor
#2
Qinxue Bao, Mingyue Zhao, Li Chen, Yu Wang, Siyuan Wu, Wenchao Wu, Xiaojing Liu
AIMS: Sigma-1 receptor (Sig-1R) is a ligand-regulated endoplasmic reticulum (ER) chaperone involved in cardiac hypertrophy, but it is not known whether Sig-1R is regulated by microRNAs (miRNAs). According to bioinformatic analysis, miR-297 was suggested as a potential target miRNA for Sig-1R. Therefore, we verified whether miR-297 could target Sig-1R and investigated the possible mechanisms underlying the role of miR-297 in cardiac hypertrophy. MAIN METHODS: Bioinformatic analysis combined with laboratory experiments, including quantitative RT-PCR, Western blotting, and luciferase assay, were performed to identify the target miRNA of Sig-1R...
March 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28267207/listeria-monocytogenes-induces-an-interferon-enhanced-activation-of-the-integrated-stress-response-that-is-detrimental-for-resolution-of-infection-in-mice
#3
Carolina Valderrama, Amy Clark, Fumihiko Urano, Emil R Unanue, Javier A Carrero
Type I interferons (IFNs) induce a detrimental response during Listeria monocytogenes (L. monocytogenes) infection. We were interested in identifying mechanisms linking IFN signaling to negative host responses against L. monocytogenes infection. Herein we found that infection of myeloid cells with L. monocytogenes led to a coordinated induction of type I IFNs and activation of the integrated stress response (ISR). Infected cells did not induce Xbp1 splicing or BiP upregulation, indicating that the unfolded protein response was not triggered...
March 7, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28237587/hepatic-mrna-expression-for-genes-related-to-somatotropic-axis-glucose-and-lipid-metabolisms-and-inflammatory-response-of-periparturient-dairy-cows-treated-with-recombinant-bovine-somatotropin
#4
P R B Silva, W J Weber, B A Crooker, R J Collier, W W Thatcher, R C Chebel
Objectives of this experiment were to evaluate the effects of recombinant bovine somatotropin (rbST) treatment of periparturient dairy cows on hepatic mRNA expression for genes related to the somatotropic axis, insulin, glucose, and lipid metabolism, inflammation, and oxidative stress. Holstein cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to 1 of 3 treatments: untreated control (n = 53), 87.5 mg of rbST (n = 56; rbST87.5), and 125 mg of rbST (n = 57; rbST125). Cows in the rbST87...
February 22, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28222747/ire1%C3%AE-xbp1-pathway-promotes-melanoma-progression-by-regulating-il-6-stat3-signaling
#5
Cheng Chen, Xuejun Zhang
BACKGROUND: The IRE1α-XBP1 pathway is the most conserved branch of the unfolded protein response pathways, which are activated during endoplasmic reticulum (ER) stress caused by the accumulation of unfolded/misfolded proteins in the ER lumen. The IRE1α-XBP1 pathway plays a critical role in various cancers. However, the role of this pathway in melanoma cell growth remains unclear. METHODS: Sixty-one pairs of melanoma specimens and corresponding normal tissues from patients were stained with XBP1...
February 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28216622/effects-of-gene-polymorphisms-in-the-endoplasmic-reticulum-stress-pathway-on-clinical-outcomes-of-chemoradiotherapy-in-chinese-patients-with-nasopharyngeal-carcinoma
#6
Xiao-Bin Guo, Wan-le Ma, Li-Juan Liu, Yu-Ling Huang, Jing Wang, Li-Hua Huang, Xiang-Dong Peng, Ji-Ye Yin, Jin-Gao Li, Shao-Jun Chen, Guo-Ping Yang, Hui Wang, Cheng-Xian Guo
There is considerable inter-individual variabil¬ity in chemoradiotherapy responses in nasopharyngeal carcinoma (NPC) patients receiv¬ing the same or similar treatment protocols. In this study we evaluated the association between the gene polymorphisms in endoplasmic reticulum (ER) stress pathway and chemoradiation responses in Chinese NPC patients. A total of 150 patients with histopathologically conformed NPC and treated with concurrent chemoradiotherapy were enrolled. Genotypes in ER stress pathway genes, including VCP (valosin-containing protein) rs2074549, HSP90B1 rs17034943, CANX (calnexin) rs7566, HSPA5 [heat shock protein family A (Hsp70) member 5] rs430397, CALCR (calcitonin receptor) rs2528521, and XBP1 (X-box binding protein 1) rs2269577 were analyzed by Sequenom MassARRAY system...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28215742/identification-of-grass-carp-ctenopharyngodon-idella-xbp1s-as-a-primary-member-in-er-stress
#7
Xiangqin Wang, Yichuan Mi, Bin Zhong, Huiling Mao, Yiqi Wan, Tao Zhang, Haizhou Wang, Chengyu Hu
X-box binding protein 1 (XBP1), a vital basic leucine zipper transcription factor for the related gene transcription in endoplasmic reticulum (ER) stress, belongs to the CREB/ATF family. In mammals, XBP1S is the activated one of XBP1 isoform. In order to study the role of fish XBP1S, we cloned and identified the XBP1S (KU509247) from grass carp (Ctenopharyngodon idella) (named CiXBP1S) by homologous cloning and RACE technique. The full length of CiXBP1S is 1694 bp along with 124 bp of 5' UTR, 418 bp of 3' UTR and the longest open reading frame (1152 bp) encoding a polypeptide of 383 amino acids with a well conserved DNA binding domain (BRLZ domain)...
February 20, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28205568/luman-contributes-to-brefeldin-a-induced-prion-protein-gene-expression-by-interacting-with-the-erse26-element
#8
Marc-André Déry, Andréa C LeBlanc
The cellular prion protein (PrP) is essential for transmissible prion diseases, but its exact physiological function remains unclear. Better understanding the regulation of the human prion protein gene (PRNP) expression can provide insight into this elusive function. Spliced XBP1 (sXBP1) was recently shown to mediate endoplasmic reticulum (ER) stress-induced PRNP expression. In this manuscript, we identify Luman, a ubiquitous, non-canonical unfolded protein response (UPR), as a novel regulator of ER stress-induced PRNP expression...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leukocytes
#9
Yi-Ping Liu, Victoria Rajamanikham, Marissa Baron, Sagar Patel, Sameer K Mathur, Elizabeth A Schwantes, Carole Ober, Daniel J Jackson, James E Gern, Robert F Lemanske, Judith A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodeling and hyper-responsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN) regulated chemokine CXCL10...
February 13, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28187708/incorporating-prior-biological-knowledge-for-network-based-differential-gene-expression-analysis-using-differentially-weighted-graphical-lasso
#10
Yiming Zuo, Yi Cui, Guoqiang Yu, Ruijiang Li, Habtom W Ressom
BACKGROUND: Conventional differential gene expression analysis by methods such as student's t-test, SAM, and Empirical Bayes often searches for statistically significant genes without considering the interactions among them. Network-based approaches provide a natural way to study these interactions and to investigate the rewiring interactions in disease versus control groups. In this paper, we apply weighted graphical LASSO (wgLASSO) algorithm to integrate a data-driven network model with prior biological knowledge (i...
February 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28167662/impaired-ire1-expression-and-xbp1-activation-is-a-hallmark-of-gcb-dlbcl-and-contributes-to-tumor-growth
#11
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/28158898/4pba-strongly-attenuates-endoplasmic-reticulum-stress-fibrosis-and-mitochondrial-apoptosis-markers-in-cyclosporine-treated-human-gingival-fibroblasts
#12
Suresh Ranga Rao, Subbarayan Rajasekaran, Supraja Ajitkumar, Murugan Girija Dinesh
Cyclosporine induces overgrowth of human gingiva. Previously we have shown (i) cyclosporine - inducing ER stress in human gingival fibroblasts, (ii) increased matrix protein expression, and (iii) interference with mitochondrial pro- and anti - apoptotic factors. This study was undertaken to assess the effects of melatonin (an antioxidant), 4PBA (an ER stress inhibitor), and simvastatin on the expression of ER Stress markers, as well as on matrix and mitochondrial markers. Human gingival fibroblasts incubated with cyclosporine, or without melatonin/4PBA/statin...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28128204/a-critical-role-of-ddrgk1-in-endoplasmic-reticulum-homoeostasis-via-regulation-of-ire1%C3%AE-stability
#13
Jiang Liu, Ying Wang, Lizhi Song, Linghua Zeng, Weiwei Yi, Ting Liu, Huanzhen Chen, Miao Wang, Zhenyu Ju, Yu-Sheng Cong
Disturbance of endoplasmic reticulum (ER) homoeostasis induces ER stress and leads to activation of the unfolded protein response (UPR), which is an adaptive reaction that promotes cell survival or triggers apoptosis, when homoeostasis is not restored. DDRGK1 is an ER membrane protein and a critical component of the ubiquitin-fold modifier 1 (Ufm1) system. However, the functions and mechanisms of DDRGK1 in ER homoeostasis are largely unknown. Here, we show that depletion of DDRGK1 induces ER stress and enhances ER stress-induced apoptosis in both cancer cells and hematopoietic stem cells (HSCs)...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28093457/functional-analysis-of-the-mammalian-rna-ligase-for-ire1-in-the-unfolded-protein-response
#14
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/28079229/the-transcription-factor-xbp1-in-memory-and-cognition-implications-in-alzheimer-disease
#15
Moustapha Cissé, Eric Duplan, Frédéric Checler
X-box binding protein 1 (XBP1) is a unique basic region leucine zipper transcription factor isolated two decades ago in a search for regulators of major histocompatibility complex class II gene expression. XBP1 is a very complex protein regulating many physiological functions, including immune system, inflammatory responses, and lipid metabolism. Evidence over the past few years suggests that XBP1 also plays important roles in pathological settings since its activity as transcription factor has profound effects on the prognosis and progression of diseases such as cancer, neurodegeneration, and diabetes...
January 4, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28065589/perk-and-xbp1-differentially-regulate-cxcl10-and-ccl2-production
#16
Shuang Zhu, Hua Liu, Haibo Sha, Ling Qi, Dian-Shuai Gao, Wenbo Zhang
Inflammation plays a key role in the pathogenesis of many retinal degenerative diseases related with photoreceptor dysfunction/degeneration. However the involvement of photoreceptor cells in inflammatory reactions is largely unknown as they are not considered as inflammatory cells. In this study, we assessed whether photoreceptor cells can produce CCL2 and CXCL10, two important players in inflammation during endoplasmic reticulum (ER) stress. After photoreceptor 661 W cells were treated with ER stress inducer thapsigargin (TG), induction of ER stress increased CXCL10 and CCL2 expression at both mRNA and protein levels, which was significantly blocked by an ER stress blocker 4-phenylbutyrate...
February 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28052118/tgf-%C3%AE-3-inhibits-antibody-production-by-human-b-cells
#17
Yumi Tsuchida, Shuji Sumitomo, Kazuyoshi Ishigaki, Akari Suzuki, Yuta Kochi, Haruka Tsuchiya, Mineto Ota, Toshihiko Komai, Mariko Inoue, Kaoru Morita, Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus...
2017: PloS One
https://www.readbyqxmd.com/read/28049460/bitter-melon-protects-against-er-stress-in-ls174t-colonic-epithelial-cells
#18
Dale A Kunde, Wai Chin Chong, Prathiba V Nerurkar, Kiran D K Ahuja, Jeremy Just, Jason A Smith, Nuri Guven, Rajaraman D Eri
BACKGROUND: Bitter Melon (BM) has been used as a functional food in traditional Chinese and Indian medicine for many generations and has gained a great deal of attention due to its apparent benefits in moderating some of the pathogenic processes in a variety of inflammatory conditions. BM extract (BME) has been shown to possess strong anti-oxidant properties. In addition, it can ameliorate oxidative stress and potentially ER stress. There is increasing evidence that oxidative and ER stress are major contributors for intestinal secretory cell dysfunction which leads to local inflammation and disease pathogenesis that are hallmarks of inflammatory bowel diseases (IBD)...
January 3, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28039913/the-unfolded-protein-response-mediates-fibrogenesis-and-collagen-i-secretion-through-regulating-tango1-in-mice
#19
Jessica L Maiers, Enis Kostallari, Malek Mushref, Thiago M deAssuncao, Haiyang Li, Nidhi Jalan-Sakrikar, Robert C Huebert, Sheng Cao, Harmeet Malhi, Vijay H Shah
Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion...
March 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#20
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
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