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https://www.readbyqxmd.com/read/29232380/inhibition-of-grp78-abrogates-radioresistance-in-oropharyngeal-carcinoma-cells-after-egfr-inhibition-by-cetuximab
#1
Chaonan Sun, Chuyang Han, Yuanjun Jiang, Ning Han, Miao Zhang, Guang Li, Qiao Qiao
The EGFR-specific mAb cetuximab is one of the most effective treatments for oropharyngeal carcinoma, while patient responses to EGFR inhibitors given alone are modest. Combination treatment with radiation can improve the efficacy of treatment through increasing radiosensitivity, while resistance to radiation after administration of cetuximab limits its efficiency. Radiation and drugs can damage the endoplasmic reticulum (ER) homeostatic state and result in ER stress (ERS), subsequently causing resistance to radiation and drugs...
2017: PloS One
https://www.readbyqxmd.com/read/29232287/the-effects-of-known-cardioprotective-drugs-on-proinflammatory-cytokine-secretion-from-human-coronary-artery-endothelial-cells
#2
Michael J Haas, Marilu Jurado-Flores, Ramadan Hammoud, Victoria Feng, Krista Gonzales, Luisa Onstead-Haas, Arshag D Mooradian
BACKGROUND: Endothelial cell dysfunction in diabetes is involved in the pathogenesis and progression of premature atherosclerosis. High-dextrose has been shown to induce both oxidative stress and endoplasmic reticulum stress in cultured human coronary artery endothelial cells (HCAEC). STUDY QUESTION: To determine whether or not several classes of cardioprotective drugs inhibit proinflammatory cytokine expression by HCAEC. MEASURES AND OUTCOMES: To determine the effects of high dextrose on expression of proinflammatory cytokines by HCAEC, cells were treated with either 5...
November 27, 2017: American Journal of Therapeutics
https://www.readbyqxmd.com/read/29230396/altered-expression-of-endoplasmic-reticulum-stress-related-genes-in-the-middle-frontal-cortex-of-subjects-with-autism-spectrum-disorder
#3
Amanda Crider, Anthony O Ahmed, Anilkumar Pillai
The endoplasmic reticulum (ER) is an important organelle responsible for the folding and sorting of proteins. Disturbances in ER homeostasis can trigger a cellular response known as the unfolded protein response, leading to accumulation of unfolded or misfolded proteins in the ER lumen called ER stress. A number of recent studies suggest that mutations in autism spectrum disorder (ASD)-susceptible synaptic genes induce ER stress. However, it is not known whether ER stress-related genes are altered in the brain of ASD subjects...
November 2017: Molecular Neuropsychiatry
https://www.readbyqxmd.com/read/29230213/transcription-factor-c-ebp-homologous-protein-in-health-and-diseases
#4
REVIEW
Yuan Yang, Lian Liu, Ishan Naik, Zachary Braunstein, Jixin Zhong, Boxu Ren
C/EBP homologous protein (CHOP), known also as DNA damage-inducible transcript 3 and as growth arrest and DNA damage-inducible protein 153 (GADD153), is induced in response to certain stressors. CHOP is universally acknowledged as a main conduit to endoplasmic reticulum stress-induced apoptosis. Ongoing research established the existence of CHOP-mediated apoptosis signaling networks, for which novel downstream targets are still being determined. However, there are studies that contradict this notion and assert that apoptosis is not the only mechanism by which CHOP plays in the development of pathologies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29230100/dl-3-n-butylphthalide-prevents-the-disruption-of-blood-spinal-cord-barrier-via-inhibiting-endoplasmic-reticulum-stress-following-spinal-cord-injury
#5
Binbin Zheng, Yulong Zhou, Hongyu Zhang, Guangyong Yang, Zhenghua Hong, Dandan Han, Qingqing Wang, Zili He, Yanlong Liu, Fenzan Wu, Xie Zhang, Songlin Tong, Huazi Xu, Jian Xiao
After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29230053/stress-induced-unfolded-protein-response-contributes-to-zika-virus-associated-microcephaly
#6
Ivan Gladwyn-Ng, Lluís Cordón-Barris, Christian Alfano, Catherine Creppe, Thérèse Couderc, Giovanni Morelli, Nicolas Thelen, Michelle America, Bettina Bessières, Férechté Encha-Razavi, Maryse Bonnière, Ikuo K Suzuki, Marie Flamand, Pierre Vanderhaeghen, Marc Thiry, Marc Lecuit, Laurent Nguyen
Accumulating evidence support a causal link between Zika virus (ZIKV) infection during gestation and congenital microcephaly. However, the mechanism of ZIKV-associated microcephaly remains unclear. We combined analyses of ZIKV-infected human fetuses, cultured human neural stem cells and mouse embryos to understand how ZIKV induces microcephaly. We show that ZIKV triggers endoplasmic reticulum stress and unfolded protein response in the cerebral cortex of infected postmortem human fetuses as well as in cultured human neural stem cells...
December 11, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/29230015/a-perk-mir-211-axis-suppresses-circadian-regulators-and-protein-synthesis-to-promote-cancer-cell-survival
#7
Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E Armeson, Steven B McMahon, Gerald B Wertheim, Chi V Dang, Davide Ruggero, Constantinos Koumenis, Serge Y Fuchs, J Alan Diehl
The unfolded protein response (UPR) is a stress-activated signalling pathway that regulates cell proliferation, metabolism and survival. The circadian clock coordinates metabolism and signal transduction with light/dark cycles. We explore how UPR signalling interfaces with the circadian clock. UPR activation induces a 10 h phase shift in circadian oscillations through induction of miR-211, a PERK-inducible microRNA that transiently suppresses both Bmal1 and Clock, core circadian regulators. Molecular investigation reveals that miR-211 directly regulates Bmal1 and Clock via distinct mechanisms...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29229999/heme-accumulation-in-endothelial-cells-impairs-angiogenesis-by-triggering-paraptosis
#8
Sara Petrillo, Deborah Chiabrando, Tullio Genova, Veronica Fiorito, Giada Ingoglia, Francesca Vinchi, Federico Mussano, Stefano Carossa, Lorenzo Silengo, Fiorella Altruda, Giorgio Roberto Merlo, Luca Munaron, Emanuela Tolosano
Heme is required for cell respiration and survival. Nevertheless, its intracellular levels need to be finely regulated to avoid heme excess, which may catalyze the production of reactive oxygen species (ROS) and promote cell death. Here, we show that alteration of heme homeostasis in endothelial cells due to the loss of the heme exporter FLVCR1a, results in impaired angiogenesis. In vitro, FLVCR1a silencing in endothelial cells causes defective tubulogenesis and poor viability due to intracellular heme accumulation...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229997/splics-a-split-green-fluorescent-protein-based-contact-site-sensor-for-narrow-and-wide-heterotypic-organelle-juxtaposition
#9
Domenico Cieri, Mattia Vicario, Marta Giacomello, Francesca Vallese, Riccardo Filadi, Tina Wagner, Tullio Pozzan, Paola Pizzo, Luca Scorrano, Marisa Brini, Tito Calì
Contact sites are discrete areas of organelle proximity that coordinate essential physiological processes across membranes, including Ca2+ signaling, lipid biosynthesis, apoptosis, and autophagy. However, tools to easily image inter-organelle proximity over a range of distances in living cells and in vivo are lacking. Here we report a split-GFP-based contact site sensor (SPLICS) engineered to fluoresce when organelles are in proximity. Two SPLICS versions efficiently measured narrow (8-10 nm) and wide (40-50 nm) juxtapositions between endoplasmic reticulum and mitochondria, documenting the existence of at least two types of contact sites in human cells...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29228618/calcium-homeostasis-and-endoplasmic-reticulum-stress-are-involved-in-salvianolic-acid-b-offered-protection-against-cardiac-toxicity-of-arsenic-trioxide
#10
Jing-Yi Zhang, Bin Zhang, Min Wang, Wei Wang, Ping Liao, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia. However, its cardiotoxicity limits ATO's widespread clinical use. Previous studies demonstrated that ATO may aggravate Ca2+ overload and promote endoplasmic reticulum stress (ERS). Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities. The present study assessed whether the Sal B protective effect was related to maintenance of Ca2+ homeostasis and inhibition of ER stress...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228221/oncogenic-potential-of-hepatitis-b-virus-subgenotype-d1-surpasses-d3-significance-in-the-development-of-hepatocellular-carcinoma
#11
Somenath Datta, Debanjali Dasgupta, Alip Ghosh, Suchandrima Ghosh, Alak Manna, Simanti Datta, Mitali Chatterjee, Abhijit Chowdhury, Soma Banerjee
Despite widespread distribution of HBV-genotype D, the clinical implications of its 9 subgenotypes (D1-D9) have not been well documented. Here, we have investigated the impact of two major circulating HBV/D-subgenotypes, D1 and D3 in Eastern India towards pathogenesis of liver disease progression to hepatocellular carcinoma (HCC). HBV-subgenotypes were determined using full-length genome sequences of HBV isolates from patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC. Impact of D1 and D3 on viral lifecycle and disease progression was assessed by several invitro assays...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29225119/d-chiro-inositol-enriched-fagopyrum-tataricum-l-gaench-extract-alleviates-mitochondrial-malfunction-and-inhibits-er-stress-jnk-associated-inflammation-in-the-endothelium
#12
Bobo Zhang, Caifeng Gao, Yunlong Li, Min Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Tartary buckwheat is a food medicine dual-use crop with healing effects on cardiovascular diseases and type2 diabetes. It has been proposed that endothelial dysfunction is the initial lesion in these diseases and it's associated with mitochondrial dysfunction, endoplasmic reticulum (ER) stress and inflammation. D-chiro-inositol (DCI) is a bioactive compound of Tartary buckwheat and is always deficit in type2 diabetes. However, it remains unknown whether DCI-enriched Tartary buckwheat extract can ameliorate mitochondrial dysfunction, ER stress and inflammation in the endothelium...
December 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29223538/curcumin-induces-osteoblast-differentiation-through-mild-endoplasmic-reticulum-stress-mediated-such-as-bmp2-on-osteoblast-cells
#13
Hyo-Eun Son, Eun-Jung Kim, Won-Gu Jang
AIMS: Curcumin (diferuloylmethane or [1E,6E]-1,7-bis[4-hydroxy-3-methoxyphenyl]-1,6heptadiene-3,5-dione) is a phenolic natural product derived from the rhizomes of the turmeric plant, Curcuma longa. It is reported to have various biological actions such as anti-oxidative, anti-inflammatory, and anti-cancer effects. However, the molecular mechanism of osteoblast differentiation by curcumin has not yet been reported. MAIN METHODS: The cytotoxicity of curcumin was identified using the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay...
December 6, 2017: Life Sciences
https://www.readbyqxmd.com/read/29221916/dna-methylation-signatures-at-endoplasmic-reticulum-stress-genes-are-associated-with-adiposity-and-insulin-resistance
#14
Omar Ramos-Lopez, Jose I Riezu-Boj, Fermin I Milagro, J Alfredo Martinez
A sustained activation of the unfolded protein response and the subsequent endoplasmic reticulum (ER) stress has been involved in the onset and severity of several metabolic diseases. The aim of this study was to analyze the association of DNA methylation signatures at ER stress genes with adiposity traits and related metabolic disorders. An epigenomic analysis within the Methyl Epigenome Network Association (MENA) project was conducted in an adult population (n=474). DNA methylation status in peripheral white blood cells was analyzed by a microarray approach...
November 28, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29221207/chst6-mutation-screening-and-endoplasmatic-reticulum-stress-in-macular-corneal-dystrophy
#15
Liyuan Wang, Xianling Tang, Xiaolin Lv, Encheng Sun, Donglai Wu, Changlin Wang, Ping Liu
Macular corneal dystrophy (MCD) is an autosomal recessive disorder mainly caused by gene mutations of carbohydrate sulfotransferase (CHST6) leading to bilateral visual impairment. Because the mechanism underlying this degeneration remains poorly understood, we investigated molecular alterations and pathways that may be involved in MCD in this issue. Different mutation sites were screened by direct sequencing of the coding region of CHST6. In addition, we described morphological changes in MCD keratocytes by light microscopy and electron microscopy and determined the relationship between the development of this disease and the occurrence of apoptosis through flow cytometry, cell counting kit-8, colony formation assay and other experiments...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221184/hepatitis-b-virus-x-protein-inhibits-apoptosis-by-modulating-endoplasmic-reticulum-stress-response
#16
Jia Li, Jiang He, Yongming Fu, Xingwang Hu, Lun-Quan Sun, Yan Huang, Xuegong Fan
Chronic Hepatitis B virus (HBV) infection is a major risk of hepatocellular carcinoma (HCC) worldwide. Hepatitis B virus X protein (HBx) is encoded by one of the four open reading frames of HBV, and is well known as an important coactivator for HBV replication and HBV-associated hepatocellular carcinogenesis. However, its role in keeping cells from apoptosis to promote HCC proliferation remains controversial. Here, we used HBx expressing HCC cells as a model, to investigate the mechanism of HBx-mediated cellular response to endoplasmic reticulum (ER) stress...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29221131/hoxa5-increases-mitochondrial-apoptosis-by-inhibiting-akt-mtorc1-s6k1-pathway-in-mice-white-adipocytes
#17
Fei Feng, Qian Ren, Song Wu, Muhammad Saeed, Chao Sun
Homeobox A5(Hoxa5), a member of the Hox family, plays a important role in the regulation of proliferation and apoptosis in cancer cells. The dysregulation of the adipocyte apoptosis in vivo leads to obesity and metabolic disorders. However, the effects of Hoxa5 on adipocyte apoptosis are still unknown. In this study, palmitic acid (PA) significantly increased the mRNA level of Hoxa5 and triggered white adipocyte apoptosis in vivo and in vitro. Further analysis revealed that Hoxa5 enhanced the early and late apoptotic cells and fragmentation of genomic DNA in adipocytes from inguinal white adipose tissue (iWAT) of mice...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220654/a-unique-isr-program-determines-cellular-responses-to-chronic-stress
#18
Bo-Jhih Guan, Vincent van Hoef, Raul Jobava, Orna Elroy-Stein, Leos S Valasek, Marie Cargnello, Xing-Huang Gao, Dawid Krokowski, William C Merrick, Scot R Kimball, Anton A Komar, Antonis E Koromilas, Anthony Wynshaw-Boris, Ivan Topisirovic, Ola Larsson, Maria Hatzoglou
The integrated stress response (ISR) is a homeostatic mechanism induced by endoplasmic reticulum (ER) stress. In acute/transient ER stress, decreased global protein synthesis and increased uORF mRNA translation are followed by normalization of protein synthesis. Here, we report a dramatically different response during chronic ER stress. This chronic ISR program is characterized by persistently elevated uORF mRNA translation and concurrent gene expression reprogramming, which permits simultaneous stress sensing and proteostasis...
December 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29215059/protective-effect-of-mesenchymal-stem-cells-on-the-pressure-ulcer-formation-by-the-regulation-of-oxidative-and-endoplasmic-reticulum-stress
#19
Sei-Ichiro Motegi, Akiko Sekiguchi, Akihiko Uchiyama, Akihito Uehara, Chisako Fujiwara, Sahori Yamazaki, Buddhini Perera, Hideharu Nakamura, Sachiko Ogino, Yoko Yokoyama, Ryoko Akai, Takao Iwawaki, Osamu Ishikawa
Cutaneous ischemia-reperfusion (I/R) injury is associated with the early pathogenesis of cutaneous pressure ulcers (PUs). The objective of this study was to investigate the effect of mesenchymal stem cells (MSCs) injection on the formation of PUs after I/R injury and determine the underlying mechanisms. We found that the subcutaneous injection of MSCs into areas of I/R injured skin significantly suppressed the formation of PUs. I/R-induced vascular damage, hypoxia, oxidative DNA damage, and apoptosis were decreased by MSCs injection...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214052/neuroprotective-role-of-retinal-sirt3-against-acute-photo-stress
#20
Norimitsu Ban, Yoko Ozawa, Hideto Osada, Jonathan B Lin, Eriko Toda, Mitsuhiro Watanabe, Kenya Yuki, Shunsuke Kubota, Rajendra S Apte, Kazuo Tsubota
SIRT3 is a key regulator of mitochondrial reactive oxygen species as well as mitochondrial function. The retina is one of the highest energy-demanding tissues, in which the regulation of reactive oxygen species is critical to prevent retinal neurodegeneration. Although previous reports have demonstrated that SIRT3 is highly expressed in the retina and important in neuroprotection, function of SIRT3 in regulating reactive oxygen species in the retina is largely unknown. In this study, we investigated the role of retinal SIRT3 in a light-induced retinal degeneration model using SIRT3 knockout mice...
2017: NPJ Aging and Mechanisms of Disease
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