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https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#1
Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M Pandak, Phillip B Hylemon, Jasmohan S Bajaj, Arun J Sanyal, Huiping Zhou
Impaired intestinal barrier function promotes the progression of various liver diseases including cholestatic liver disease. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut-liver axis. It has been reported that bile duct ligation (BDL)-induced liver fibrosis is significantly reduced in C/EBP homologous protein knock out (CHOP(-/-) ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic ER stress responses after 1 day, which return to normal after 3 days...
September 19, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28924347/the-mechanisms-of-graphene-based-materials-induced-programmed-cell-death-a-review-of-apoptosis-autophagy-and-programmed-necrosis
#2
REVIEW
Lingling Ou, Shaoqiang Lin, Bin Song, Jia Liu, Renfa Lai, Longquan Shao
Graphene-based materials (GBMs) are widely used in many fields, including biomedicine. To date, much attention had been paid to the potential unexpected toxic effects of GBMs. Here, we review the recent literature regarding the impact of GBMs on programmed cell death (PCD). Apoptosis, autophagy, and programmed necrosis are three major PCDs. Mechanistic studies demonstrated that the mitochondrial pathways and MAPKs (JNK, ERK, and p38)- and TGF-β-related signaling pathways are implicated in GBMs-induced apoptosis...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28923347/sulforaphane-improves-disrupted-er-mitochondria-interactions-and-suppresses-exaggerated-hepatic-glucose-production
#3
Emily Tubbs, Annika S Axelsson, Guillaume Vial, Claes B Wollheim, Jennifer Reuisset, Anders H Rosengren
AIMS: Exaggerated hepatic glucose production is one of the hallmarks of type 2 diabetes. Sulforaphane (SFN) has been suggested as a new potential anti-diabetic compound. However, the effects of SFN in hepatocytes are yet unclear. Accumulating evidence points to the close structural contacts between the ER and mitochondria, known as mitochondria-associated ER membranes (MAMs), as important hubs for hepatic metabolism. We wanted to investigate whether SFN could affect hepatic glucose production and MAMs...
September 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28923079/endoplasmic-reticulum-stress-cooperates-with-toll-like-receptor-ligation-in-driving-activation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#4
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/28922472/mirna-506-promotes-primary-biliary-cholangitis-like-features-in-cholangiocytes-and-immune-activation
#5
Oihane Erice, Patricia Munoz-Garrido, Javier Vaquero, Maria J Perugorria, Maite G Fernandez-Barrena, Elena Saez, Alvaro Santos-Laso, Ander Arbelaiz, Raul Jimenez-Agüero, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Verónica Torrano, Arkaitz Carracedo, Meenakshisundaram Ananthanarayanan, Marco Marzioni, Jesus Prieto, Ulrich Beuers, Ronald P Oude Elferink, Nicholas F LaRusso, Luis Bujanda, Jose J G Marin, Jesus M Banales
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase complex-E2 (PDC-E2) is a common feature. MicroRNA (miR) dysregulation occurs in liver and immune cells of PBC patients, but their functional relevance is largely unknown. We previously reported that miR-506 is overexpressed in PBC cholangiocytes and directly targets both Cl(-) /HCO3(-) anion exchanger 2 (AE2) and type III inositol 1,4,5-trisphosphate receptor (InsP3R3), leading to cholestasis...
September 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28921920/research-highlights
#6
(no author information available yet)
In this issue, we highlight a study by Li and colleagues describing how long-chain sphingolipids maintain the asymmetrical distribution of multidrug resistance transporters between mother and daughter cells, a paper by Morley and colleagues highlighting a role for DDX3X RNA helicase in the spatial localisation of the translational machinery in migrating cells and a report by Metzen and colleagues on opposing roles of two luminal ER oxidoreductases in the regulation PERK-mediated signalling during ER stress.
September 2017: FEBS Journal
https://www.readbyqxmd.com/read/28921568/neuronal-activity-dependent-local-activation-of-dendritic-unfolded-protein-response-promotes-expression-of-brain-derived-neurotrophic-factor-in-cell-soma
#7
Atsushi Saito, Longjie Cai, Koji Matsuhisa, Yosuke Ohtake, Masayuki Kaneko, Soshi Kanemoto, Rie Asada, Kazunori Imaizumi
Unfolded protein response (UPR) has roles not only in resolving the accumulation of unfolded proteins owing to endoplasmic reticulum (ER) stress, but also in regulation of cellular physiological functions. ER stress transducers providing the branches of UPR signaling are known to localize in distal dendritic ER of neurons. These reports suggest that local activation of UPR branches may produce integrated outputs for distant communication, and allow regulation of local events in highly polarized neurons. Here, we demonstrated that synaptic activity- and brain-derived neurotrophic factor (BDNF)-dependent local activation of UPR signaling could be associated with dendritic functions through retrograde signal propagation by using murine neuroblastoma cell line, Neuro-2A and primary cultured hippocampal neurons derived from postnatal day 0 litter C57BL/6 mice...
September 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28920921/increased-intracellular-proteolysis-reduces-disease-severity-in-an-er-stress-associated-dwarfism
#8
Lorna A Mullan, Ewa J Mularczyk, Louise H Kung, Mitra Forouhan, Jordan Ma Wragg, Royston Goodacre, John F Bateman, Eileithyia Swanton, Michael D Briggs, Raymond P Boot-Handford
The short-limbed dwarfism metaphyseal chondrodysplasia type Schmid (MCDS) is linked to mutations in type X collagen, which increase ER stress by inducing misfolding of the mutant protein and subsequently disrupting hypertrophic chondrocyte differentiation. Here, we show that carbamazepine (CBZ), an autophagy-stimulating drug that is clinically approved for the treatment of seizures and bipolar disease, reduced the ER stress induced by 4 different MCDS-causing mutant forms of collagen X in human cell culture...
September 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28919256/metabolic-links-between-plasma-cell-survival-secretion-and-stress
#9
REVIEW
Wing Y Lam, Deepta Bhattacharya
Humoral immunity is generated and maintained by antigen-specific antibodies that counter infectious pathogens. Plasma cells are the major producers of antibodies during and after infections, and each plasma cell produces some thousands of antibody molecules per second. This magnitude of secretion requires enormous quantities of amino acids and glycosylation sugars to properly build and fold antibodies, biosynthetic substrates to fuel endoplasmic reticulum (ER) biogenesis, and additional carbon sources to generate energy...
September 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28918898/endoplasmic-reticulum-transport-of-glutathione-by-sec61-is-regulated-by-ero1-and-bip
#10
Alise J Ponsero, Aeid Igbaria, Maxwell A Darch, Samia Miled, Caryn E Outten, Jakob R Winther, Gael Palais, Benoit D'Autréaux, Agnès Delaunay-Moisan, Michel B Toledano
In the endoplasmic reticulum (ER), Ero1 catalyzes disulfide bond formation and promotes glutathione (GSH) oxidation to GSSG. Since GSSG cannot be reduced in the ER, maintenance of the ER glutathione redox state and levels likely depends on ER glutathione import and GSSG export. We used quantitative GSH and GSSG biosensors to monitor glutathione import into the ER of yeast cells. We found that glutathione enters the ER by facilitated diffusion through the Sec61 protein-conducting channel, while oxidized Bip (Kar2) inhibits transport...
September 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28918467/anisodamine-inhibits-endoplasmic-reticulum-stress-associated-txnip-nlrp3-inflammasome-activation-in-rhabdomyolysis-induced-acute-kidney-injury
#11
Xiaopeng Yuan, Yitao Zheng, Chuanbao Chen, Changxi Wang
Anisodamine protects against free radical-induced cellular damage. This study aimed to investigate the protective effect of anisodamine on rhabdomyolysis-induced acute kidney injury (RIAKI). C57BL/6 J mice, TXNIP(-/-) and NLRP3 (-/-) (both were C57BL/6 J background) mice were used to construct RIAKI model. Anisodamine administration was performed on RIAKI mice only. Mice were divided into control, TXNIP-KD (knock down), LNPR3-KD, and anisodamine group (n = 15 in each group). The renal injury, renal function, renal tubular cells apoptosis and expression of Caspase-1, ASC, endoplasmic reticulum (ER) stress markers IRE-1α, CHOP, and ATF4, and interleukin (IL-1α, IL-1β, and IL-18) were detected...
September 16, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28917840/both-nitric-oxide-and-nitrite-prevent-homocysteine-induced-endoplasmic-reticulum-stress-and-subsequent-apoptosis-via-cgmp-dependent-pathway-in-neuronal-cells
#12
Sun-Oh Jeong, Yong Son, Ju Hwan Lee, Seung Won Choi, Sung Hun Kim, Yong-Kwan Cheong, Hun-Taeg Chung, Hyun-Ock Pae
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells...
September 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28916474/nox4-regulates-the-enos-uncoupling-process-in-aging-endothelial-cells
#13
Hwa-Young Lee, Hyung-Ryong Kim, Han-Jung Chae
ROS and its associated signaling contribute to vascular aging-associated endothelial disturbance. Since the non-effective endothelial nitric oxide synthase (eNOS) coupling status is related to vascular aging-related phenotypes, eNOS coupled/uncoupled system signaling was studied in human umbilical vein endothelial cells (HUVEC). Nitric oxide (NO) and eNOS Ser1177 were significantly decreased, whereas O2(-) (superoxide anion radical) increased with passage number. In aging cells, NADPH oxidase 4 (Nox4), one of the main superoxide generating enzymes, and its associated protein disulfide isomerase (PDI) chaperone were highly activated, and the resultant ER redox imbalance leads to disturbance of protein folding capability, namely endoplasmic reticulum (ER) stress, ultimately inducing dissociation between HSP90 and IRE-1α or PERK, decreasing HSP90 stability and dissociating the binding of eNOS from the HSP90 and leading to eNOS uncoupling...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28915644/phytoagent-deoxyelephantopin-derivative-inhibits-triple-negative-breast-cancer-cell-activity-by-inducing-oxidative-stress-mediated-paraptosis-like-cell-death
#14
Jeng-Yuan Shiau, Kyoko Nakagawa-Goto, Kuo-Hsiung Lee, Lie-Fen Shyur
Triple negative breast cancer (TNBC) is a highly metastatic cancer among the breast cancer subgroups. A thorny issue for clinical therapy of TNBC is lack of an efficient targeted therapeutic strategy. We previously created a novel sesquiterpene lactone analog (named DETD-35) derived from plant deoxyelephantopin (DET) which exhibits potent effects against human TNBC MDA-MB-231 tumor growth in a xenograft mouse model. Here we studied the mechanisms of both DET and DETD-35 against MDA-MB-231 cells. DETD-35 (3-fold decreased in IC50) exhibited better anti-TNBC cell activity than DET as observed through induction of reactive oxygen species production (within 2 h treatment) and damage to the ER structures, resulting in ER-derived cytoplasmic vacuolation and ubiquitinated protein accumulation in the treated cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915587/expression-and-release-of-glucose-regulated-protein-78-grp78-in-multiple-myeloma
#15
Normann Steiner, Bojana Borjan, Roman Hajek, Karin Jöhrer, Georg Göbel, Wolfgang Willenbacher, Johann Kern, Eberhard Gunsilius, Gerold Untergasser
INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912266/lysine-trimethylation-regulates-78-kda-glucose-regulated-protein-proteostasis-during-endoplasmic-reticulum-stress
#16
Jonas Sieber, Nicolas Wieder, Mauricio Ostrosky-Frid, Moran Dvela-Levitt, Ozan Aygün, Namrata D Udeshi, Steven A Carr, Anna Greka
The upregulation of chaperones such as the 78-kDa glucose-regulated protein (GRP78; also referred to as BiP or HSPA5) is part of the adaptive cellular response to endoplasmic reticulum (ER) stress. GRP78 is widely used as a marker of the unfolded protein response, associated with sustained ER stress. Here, we report the discovery of a proteostatic mechanism involving GRP78 trimethylation in the context of ER stress. Using mass spectrometry-based proteomics, we identified two GRP78 fractions, one homeostatic and one induced by ER stress...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911649/long-chain-bases-from-sea-cucumber-mitigate-endoplasmic-reticulum-stress-and-inflammation-in-obesity-mice
#17
Shiwei Hu, Jinhui Wang, Jingfeng Wang, Changhu Xue, Yuming Wang
Endoplasmic reticulum (ER) stress and inflammation can induce hyperglycemia. Long-chain bases (LCBs) from sea cucumber exhibit antihyperglycemic activities. However, their effects on ER stress and inflammation are unknown. We investigated the effects of LCBs on ER stress and inflammatory response in high-fat, fructose diet-induced obesity mice. Reactive oxygen species and free fatty acids were measured. Inflammatory cytokines in serum and their mRNA expressions in epididymal adipose tissues were investigated...
July 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28906486/small-molecule-rl71-triggered-excessive-autophagic-cell-death-as-a-potential-therapeutic-strategy-in-triple-negative-breast-cancer
#18
Jian Gao, Minmin Fan, Shuang Peng, Minxia Zhang, Gang Xiang, Xin Li, Wenjie Guo, Yang Sun, Xuefeng Wu, Xudong Wu, Guang Liang, Yan Shen, Qiang Xu
Triple-negative breast cancer (TNBC) has an aggressive phenotype and a poor prognosis owing to the high propensity for metastatic progression and the absence of specific targeted treatment. Here, we revealed that small-molecule RL71 targeting sarco/endoplasmic reticulum calcium-ATPase 2 (SERCA2) exhibited potent anti-cancer activity on all TNBC cells tested. Apart from apoptosis induction, RL71 triggered excessive autophagic cell death, the main contributor to RL71-induced TNBC cell death. RL71 augmented the release of Ca(2+) from the endoplasmic reticulum (ER) into the cytosol by inhibiting SERCA2 activity...
September 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28906388/retrospective-cause-analysis-of-troponin-i-elevation-in-non-cad-patients-special-emphasis-on-sepsis
#19
Chien-Wen Yang, Huijun Li, Lisa Thomas, Manuel Ramos, Po-Hong Liu, Thomas Roe, Ravinder Valadri, Michael C Kiel, Vincent Yi-Fong Su, Qi Shi
BACKGROUND: Troponin I is one of the most commonly tested biochemical markers in the emergency room (ER) and in the hospital setting. Besides coronary artery disease (CAD), demand ischemia with underlying tachycardia, anemia, hypertensive emergency, congestive heart failure, kidney disease, sepsis, and pulmonary embolism have also been reported to cause troponin I elevations. Few reports have excluded patients with CAD, and no study has summarized the proportion of these factors relative to an increased troponin I level...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#20
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
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