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https://www.readbyqxmd.com/read/28817638/the-transcriptional-profiling-of-human-in-vivo-generated-plasma-cells-identifies-selective-imbalances-in-monoclonal-gammopathies
#1
Luis M Valor, Beatriz Rodríguez-Bayona, Ana B Ramos-Amaya, José A Brieva, Antonio Campos-Caro
Plasma cells (PC) represent the heterogeneous final stage of the B cells (BC) differentiation process. To characterize the transition of BC into PC, transcriptomes from human naïve BC were compared to those of three functionally-different subsets of human in vivo-generated PC: i) tonsil PC, mainly consisting of early PC; ii) PC released to the blood after a potent booster-immunization (mostly cycling plasmablasts); and, iii) bone marrow CD138+ PC that represent highly mature PC and include the long-lived PC compartment...
2017: PloS One
https://www.readbyqxmd.com/read/28817601/bortezomib-initiates-endoplasmic-reticulum-stress-elicits-autophagy-and-death-in-echinococcus-granulosus-larval-stage
#2
María Celeste Nicolao, Julia A Loos, Christian Rodriguez Rodrigues, Viviana Beas, Andrea C Cumino
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28775151/the-requirement-of-ire1-xbp1-in-resolving-physiological-stress-during-drosophila-development
#3
Huai-Wei Huang, Xiaomei Zeng, Taiyoun Rhim, David Ron, Hyung Don Ryoo
IRE1 mediates the Unfolded Protein Response (UPR) in part by regulating XBP1 mRNA splicing in response to endoplasmic reticulum (ER) stress. In cultured metazoan cells, IRE1 also exhibits XBP1-independent biochemical activities. IRE1 and XBP1 are developmentally essential genes in Drosophila and mammals, but the source of the physiological ER stress and the relative contributions of XBP1 activation versus other IRE1 functions to development remain unknown. Here, employed Drosophila to address this question...
August 3, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28757346/development-of-an-xbp1-agonist-hlj2-as-a-potential-therapeutic-agent-for-ulcerative-colitis
#4
HaiJing Zhang, ZhiHui Zhang, GuangMing Song, XiaoNan Tang, HuaChen Song, AnJun Deng, WenJie Wang, LianQiu Wu, Hailin Qin
There is a severe lack of effective treatments for ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. The identification of valid targets and new drugs is an urgent need. In this study, we identified the XBP-1 agonist HLJ2 as a promising treatment candidate. In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myeloperoxidase (MPO) activity and reduced production of the inflammatory cytokines TNF-α, IL-1β, and IL-6...
July 28, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28747426/intestinal-epithelial-cell-endoplasmic-reticulum-stress-promotes-mult1-up-regulation-and-nkg2d-mediated-inflammation
#5
Shuhei Hosomi, Joep Grootjans, Markus Tschurtschenthaler, Niklas Krupka, Juan D Matute, Magdalena B Flak, Eduardo Martinez-Naves, Manuel Gomez Del Moral, Jonathan N Glickman, Mizuki Ohira, Lewis L Lanier, Arthur Kaser, Richard Blumberg
Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1(ΔIEC) ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein...
July 26, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28743992/endotoxemia-mediated-activation-of-acetyltransferase-p300-impairs-insulin-signaling-in-obesity
#6
Jia Cao, Jinghua Peng, Hongying An, Qiyi He, Tatiana Boronina, Shaodong Guo, Morris F White, Philip A Cole, Ling He
Diabetes and obesity are characterized by insulin resistance and chronic low-grade inflammation. An elevated plasma concentration of lipopolysaccharide (LPS) caused by increased intestinal permeability during diet-induced obesity promotes insulin resistance in mice. Here, we show that LPS induces endoplasmic reticulum (ER) stress and protein levels of P300, an acetyltransferase involved in glucose production. In high-fat diet fed and genetically obese ob/ob mice, P300 translocates from the nucleus into the cytoplasm of hepatocytes...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28717189/cdk5-mediated-phosphorylation-of-xbp1s-contributes-to-its-nuclear-translocation-and-activation-in-mpp-induced-parkinson-s-disease-model
#7
Feng-Juan Jiao, Qing-Zhi Wang, Pei Zhang, Jian-Guo Yan, Zheng Zhang, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Bo Tian
Parkinson's disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP(+)-treated neurons...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28707320/homology-model-of-the-human-trna-splicing-ligase-rtcb
#8
Argha Nandy, Patricia Saenz-Mendez, Adrienne M Gorman, Afshin Samali, Leif A Eriksson
RtcB is an essential human tRNA ligase required for ligating the 2',3'-cyclic phosphate and 5'-hydroxyl termini of cleaved tRNA halves during tRNA splicing and XBP1 fragments during endoplasmic reticulum stress. Activation of XBP1 has been implicated in various human tumors including breast cancer. Here we present, for the first time, a homology model of human RtcB (hRtcB) in complex with manganese and covalently bound GMP built from the Pyrococcus horikoshii RtcB (bRtcB) crystal structure, PDB ID 4DWQA. The structure is analyzed in terms of stereochemical quality, folding reliability, secondary structure similarity with bRtcB, druggability of the active site binding pocket and its metal-binding microenvironment...
July 13, 2017: Proteins
https://www.readbyqxmd.com/read/28687614/signal-integration-at-the-pi3k-p85-xbp1-hub-endows-coagulation-protease-activated-protein-c-with-insulin-like-function
#9
Thati Madhusudhan, Hongjie Wang, Sanchita Ghosh, Wei Dong, Varun Kumar, Moh'd Mohanad Al-Dabet, Jayakumar Manoharan, Sumra Nazir, Ahmed Elwakiel, Fabian Bock, Shrey Kohli, Andi Marquardt, Ibrahim Sögüt, Khurrum Shahzad, Andreas J Müller, Charles T Esmon, Peter P Nawroth, Jochen Reiser, Triantafyllos Chavakis, Wolfram Ruf, Berend Isermann
Coagulation proteases have increasingly recognized functions beyond hemostasis and thrombosis. Disruption of activated protein C (aPC) or insulin signaling both impair function of podocytes and ultimately cause dysfunction of the glomerular filtration barrier and diabetic kidney disease (DKD). We here show that insulin and aPC converge on a common spliced-X-box binding protein-1 (sXBP1) signaling pathway to maintain endoplasmic reticulum (ER)-homeostasis. Analogous to insulin, physiological levels of aPC maintain endoplasmic reticulum (ER) proteostasis in DKD...
July 7, 2017: Blood
https://www.readbyqxmd.com/read/28675985/hydrogen-alleviates-hyperoxic-acute-lung-injury-related-endoplasmic-reticulum-stress-in-rats-through-upregulation-of-sirt1
#10
Qiang Sun, Wenjie Han, Huijun Hu, Danfeng Fan, Yanbo Li, Yu Zhang, Yan Lv, Mingxin Li, Shuyi Pan
Hyperoxic acute lung injury (HALI) is a major clinical problem for patients undergoing supplemental oxygen therapy. Currently in clinical settings there exist no effective means of prevention or treatment methods. Our previous study found that: hydrogen could reduce HALI, as well as oxidative stress. This research will further explore the mechanism underlying the protective effect of hydrogen on oxygen toxicity. Rats were randomly assigned into three experimental groups and were exposed in a oxygen chamber for 60 continuous hours: 100% balanced air (control); 100% oxygen (HALI); 100% oxygen with hydrogen treatment (HALI + HRS)...
July 21, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28667325/xbp1-foxo1-interaction-regulates-er-stress-induced-autophagy-in-auditory-cells
#11
Akihiro Kishino, Ken Hayashi, Chiaki Hidai, Takeshi Masuda, Yasuyuki Nomura, Takeshi Oshima
The purpose of this study was to clarify the relationship among X-box-binding protein 1 unspliced, spliced (XBP1u, s), Forkhead box O1 (FoxO1) and autophagy in the auditory cells under endoplasmic reticulum (ER) stress. In addition, the relationship between ER stress that causes unfolded protein response (UPR) and autophagy was also investigated. The present study reported ER stress induction by tunicamycin treatment that resulted in IRE1α-mediated XBP1 mRNA splicing and autophagy. XBP1 mRNA splicing and FoxO1 were found to be involved in ER stress-induced autophagy...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28663129/molecular-characterization-and-expression-pattern-of-x-box-binding-protein-1-xbp1-in-common-carp-cyprinus-carpio-l-indications-for-a-role-of-xbp1-in-antibacterial-and-antiviral-immunity
#12
Ting Li, Hua Li, Shaoqing Peng, Fumiao Zhang, Liguo An, Guiwen Yang
X box-binding protein-1 (XBP1) is a transcription factor that is essential for the unfolded protein response (UPR) and the differentiation of plasma cells, and some findings have also uncovered its function in innate immunity. XBP1 typically has two different transcripts, un-spliced (XBP1u) and spliced forms (XBP1s), but XBP1s is an active transcription factor in the regulation of target genes. To date, there is no evidence about the identification and function of XBP1 in common carp. Moreover, no data are currently available regarding the role of fish XBP1 in innate immunity...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28641197/effects-of-organophosphorus-flame-retardant-tdcpp-on-normal-human-corneal-epithelial-cells-implications-for-human-health
#13
Ping Xiang, Rong-Yan Liu, Chao Li, Peng Gao, Xin-Yi Cui, Lena Q Ma
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC50 at 202 μg/mL...
June 19, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28631090/subclinical-cutaneous-inflammation-remained-after-permeability-barrier-disruption-enhances-uv-sensitivity-by-altering-er-stress-responses-and-topical-pseudoceramide-prevents-them
#14
Sang Eun Lee, Yutaka Takagi, Takahiro Nishizaka, Ji Hwoon Baek, Han Jo Kim, Seung Hun Lee
Stratum corneum forms the UV barrier. The effect of ultraviolet B (UVB) on normal skin was extensively studied; however, its effect on barrier perturbed skin remains undefined. Both barrier perturbation and UVB irradiation induce endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in keratinocytes. Mild ER stress activates homeostatic UPR, while severe ER stress leads to abnormal UPR, promoting apoptosis and inflammation. Here, we investigated UV sensitivity and UVB-induced UPR in barrier-disrupted human skin and the effects of pseudoceramide-dominant emollient on UVB-induced skin responses...
June 19, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28624220/tat-hafgf14-154-upregulates-adam10-to-attenuate-the-alzheimer-phenotype-of-app-ps1-mice-through-the-pi3k-creb-ire1%C3%AE-xbp1-pathway
#15
Tian Meng, Qin Cao, Peng Lei, Ashley I Bush, Qi Xiang, Zhijian Su, Xiang He, Jack T Rogers, Ing-Ming Chiu, Qihao Zhang, Yadong Huang
Acid fibroblast growth factor (aFGF) has shown neuroprotection in Alzheimer's disease (AD) models in previous studies, yet its mechanism is still uncertain. Here we report that the efficacy of Tat-haFGF14-154 is markedly increased when loaded cationic liposomes for intranasal delivery are intranasally administered to APP/PS1 mice. Our results demonstrated that liposomal Tat-haFGF14-154 treatment significantly ameliorated behavioral deficits, relieved brain Aβ burden, and increased the expression and activity of disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in the brain...
June 16, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28622016/endoplasmic-reticulum-stress-is-involved-in-nucleus-pulposus-degeneration-and-attenuates-low-ph-induced-apoptosis-of-rat-nucleus-pulposus-cells
#16
Zhi-Yang Xie, Lu Chen, Feng Wang, Lei Liu, Cong Zhang, Kun Wang, Feng Cai, Arjun Sinkemanni, Xin Hong, Xiao-Tao Wu
The microenvironment of degenerative intervertebral disk (IVD) is characteristic of a high concentration of lactic acid and low pH levels, whereas the underlying mechanism has not been clearly defined. Endoplasmic reticulum (ER) is the hub of interactions between environmental signals and cellular biological functions, the malfunction of which is closely involved in the pathogenesis of multiple disorders, including IVD degeneration (IVDD). This research mainly aims at exploring what role ER stress plays in the natural process of IVDD and pH-induced apoptosis of rat nucleus pulposus (NP) cells (NPCs)...
August 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28620068/x-box-binding-protein-1-dependent-plasma-cell-responses-limit-the-development-of-atherosclerosis
#17
Andrew P Sage, Meritxell Nus, Jayashree Bagchi Chakraborty, Dimitrios Tsiantoulas, Stephen A Newland, Alison J Finigan, Leanne Masters, Christoph J Binder, Ziad Mallat
Rationale: Diverse B cell responses and functions may be involved in atherosclerosis. Protective antibody responses, such as those against oxidized lipid epitopes, are thought to mainly derive from T cell-independent innate B cell subsets. In contrast, both pathogenic and protective roles have been associated with T cell-dependent antibodies and their importance in both humans and mouse models is still unclear. Objective: To specifically target antibody production by plasma cells and determine the impact on atherosclerotic plaque development in mice with and without CD4+ T cells...
June 15, 2017: Circulation Research
https://www.readbyqxmd.com/read/28614720/cellular-stress-in-the-context-of-an-inflammatory-environment-supports-tgf-%C3%AE-independent-t-helper-17-differentiation
#18
Verena Brucklacher-Waldert, Cristina Ferreira, Marisa Stebegg, Olivier Fesneau, Silvia Innocentin, Julien C Marie, Marc Veldhoen
T helper-17 (Th17) cells are associated with inflammatory disorders and cancer. We report that environmental conditions resulting in cellular stress, such as low oxygen, glucose, and isotonic stress, particularly enhance the generation of Th17 cells. Pharmacological inhibition of cell stress reduces Th17 cell differentiation while stress inducers enhance the development of Th17 cells. The cellular stress response results in Th17 cell development via sustained cytoplasmic calcium levels and, in part, XBP1 activity...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28606465/ubiquitin-proteasome-system-and-er-stress-in-the-retina-of-diabetic-rats
#19
Karnam Shruthi, Singareddy Sreenivasa Reddy, Geereddy Bhanuprakash Reddy
PURPOSE: Diabetic retinopathy (DR) is the most frequently occurring complication of diabetes. Alterations in ubiquitin-proteasome system (UPS) have been associated with several degenerative disorders. Hence, in this study, we investigated the status and role of UPS and ER stress in the retina of diabetic rats. METHODS: Diabetes was induced in rats by streptozotocin. Retinal markers, ER stress markers, components of UPS, ERAD, and autophagy were analyzed after 2- and 4-months of diabetes...
August 1, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28604593/melatonin-modulates-neuronal-cell-death-induced-by-endoplasmic-reticulum-stress-under-insulin-resistance-condition
#20
Juhyun Song, Oh Yoen Kim
Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells...
June 10, 2017: Nutrients
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