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https://www.readbyqxmd.com/read/28677092/amelioration-of-bleomycin-induced-pulmonary-fibrosis-by-chlorogenic-acid-through-endoplasmic-reticulum-stress-inhibition
#1
Yi-Chun Wang, Jing Dong, Jing Nie, Ji-Xiang Zhu, Hui Wang, Qiong Chen, Jun-Yi Chen, Jia-Mei Xia, Wei Shuai
To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration...
July 4, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28559483/endoplasmic-reticulum-stress-caused-by-lipoprotein-accumulation-suppresses-immunity-against-bacterial-pathogens-and-contributes-to-immunosenescence
#2
Jogender Singh, Alejandro Aballay
The unfolded protein response (UPR) is a stress response pathway that is activated upon increased unfolded and/or misfolded proteins in the endoplasmic reticulum (ER), and enhanced ER stress response prolongs life span and improves immunity. However, the mechanism by which ER stress affects immunity remains poorly understood. Using the nematode Caenorhabditis elegans, we show that mutations in the lipoproteins vitellogenins, which are homologs of human apolipoprotein B-100, resulted in upregulation of the UPR...
May 30, 2017: MBio
https://www.readbyqxmd.com/read/28493544/recurrence-patterns-following-irreversible-electroporation-for-hepatic-malignancies
#3
Russell C Langan, Debra A Goldman, Michael I D'Angelica, Ronald P DeMatteo, Peter J Allen, Vinod P Balachandran, William R Jarnagin, T Peter Kingham
BACKGROUND: Irreversible electroporation (IRE) has emerged as a novel, safe ablative therapy for peri-vascular lesions. However, there remains a paucity of data on long-term outcomes. METHODS: We identified patients who underwent open IRE (1/2011-6/2015) for primary and secondary hepatic malignancies. Local ablation-zone recurrence (LR) was determined by cross-sectional imaging. Cumulative incidence (CumI) of LR was calculated and a competing risks regression assessed factors associated with LR...
May 11, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28423496/mtor-inhibitors-activate-perk-signaling-and-favor-viability-of-gastrointestinal-neuroendocrine-cell-lines
#4
Patricia Freis, Julien Bollard, Justine Lebeau, Patrick Massoma, Joëlle Fauvre, Cécile Vercherat, Thomas Walter, Serge Manié, Colette Roche, Jean-Yves Scoazec, Carole Ferraro-Peyret
mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently activated in cancer cells. The mTOR pathway has been shown to be up-regulated in most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known about the UPR status in neoplastic neuroendocrine cells. However, these hormone-producing cells are likely to present distinctive adaptations of this pathway, as other secretory cells. We therefore analyzed the status of the three axes of UPR and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors (GI-NET) cell lines STC-1 and GluTag...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28395113/a-novel-role-for-crtc2-in-hepatic-cholesterol-synthesis-through-srebp-2
#5
Yujie Li, Yongfeng Song, Meng Zhao, Yanjing Guo, Chunxiao Yu, Wenbin Chen, Shanshan Shao, Chao Xu, Xinli Zhou, Lifang Zhao, Zhenhai Zhang, Tao Bo, Yu Xia, Christopher G Proud, Xuemin Wang, Li Wang, Jiajun Zhao, Ling Gao
Cholesterol synthesis is regulated by the transcription factor sterol regulatory element binding protein 2 (SREBP-2) and its target gene 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is the rate-limiting enzyme in cholesterol synthesis. Cyclic adenosine monophosphate-responsive element (CRE) binding protein-regulated transcription coactivator (CRTC) 2 is the master regulator of glucose metabolism. However, the effect of CRTC2 on cholesterol and its potential molecular mechanism remain unclear...
August 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28212571/activation-of-jnk-and-ire1-is-critically-involved-in-tanshinone-i-induced-p62-dependent-autophagy-in-malignant-pleural-mesothelioma-cells-implication-of-p62-uba-domain
#6
Jihyun Lee, Eun Jung Sohn, Sangwook Yoon, Gunho Won, Chang Geun Kim, Ji Hoon Jung, Sung-Hoon Kim
The aim of present study is to elucidate autophagic mechanism of tanshinone I (Tan I) in H28 and H2452 mesothelioma cells. Herein, Tan I exerted cytotoxicity with autophagic features of autophagy protein 5 (ATG5)/ microtubule-associated protein 1A/1B-light chain 3II (LC3 II) activation, p62/sequestosome 1 (SQSTM1) accumulation and increased number of LC3II punctae, acridine orange-stained cells and autophagic vacuoles. However, 3-methyladenine (3MA) and NH4Cl increased cytotoxicity in Tan I treated H28 cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28114319/reduced-insulin-insulin-like-growth-factor-receptor-signaling-mitigates-defective-dendrite-morphogenesis-in-mutants-of-the-er-stress-sensor-ire-1
#7
Yehuda Salzberg, Andrew J Coleman, Kevin Celestrin, Moran Cohen-Berkman, Thomas Biederer, Sivan Henis-Korenblit, Hannes E Bülow
Neurons receive excitatory or sensory inputs through their dendrites, which often branch extensively to form unique neuron-specific structures. How neurons regulate the formation of their particular arbor is only partially understood. In genetic screens using the multidendritic arbor of PVD somatosensory neurons in the nematode Caenorhabditis elegans, we identified a mutation in the ER stress sensor IRE-1/Ire1 (inositol requiring enzyme 1) as crucial for proper PVD dendrite arborization in vivo. We further found that regulation of dendrite growth in cultured rat hippocampal neurons depends on Ire1 function, showing an evolutionarily conserved role for IRE-1/Ire1 in dendrite patterning...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28067773/a-systems-biological-view-of-life-and-death-decision-with-respect-to-endoplasmic-reticulum-stress-the-role-of-perk-pathway
#8
Margita Márton, Anita Kurucz, Beáta Lizák, Éva Margittai, Gábor Bánhegyi, Orsolya Kapuy
Accumulation of misfolded/unfolded proteins in the endoplasmic reticulum (ER) leads to the activation of three branches (Protein kinase (RNA)-like endoplasmic reticulum kinase [PERK], Inositol requiring protein 1 [IRE-1] and Activating trascription factor 6 [ATF6], respectively) of unfolded protein response (UPR). The primary role of UPR is to try to drive back the system to the former or a new homeostatic state by self-eating dependent autophagy, while excessive level of ER stress results in apoptotic cell death...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27783938/vitamin-d-promotes-protein-homeostasis-and-longevity-via-the-stress-response-pathway-genes-skn-1-ire-1-and-xbp-1
#9
Karla A Mark, Kathleen J Dumas, Dipa Bhaumik, Birgit Schilling, Sonnet Davis, Tal Ronnen Oron, Dylan J Sorensen, Mark Lucanic, Rachel B Brem, Simon Melov, Arvind Ramanathan, Bradford W Gibson, Gordon J Lithgow
Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27690135/mutations-in-nonessential-eif3k-and-eif3l-genes-confer-lifespan-extension-and-enhanced-resistance-to-er-stress-in-caenorhabditis-elegans
#10
Douglas J Cattie, Claire E Richardson, Kirthi C Reddy, Elan M Ness-Cohn, Rita Droste, Mary K Thompson, Wendy V Gilbert, Dennis H Kim
The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27630541/cerebral-microvascular-endothelial-cell-apoptosis-after-ischemia-role-of-enolase-phosphatase-1-activation-and-aci-reductone-dioxygenase-1-translocation
#11
Yuan Zhang, Ting Wang, Ke Yang, Ji Xu, Lijie Ren, Weiping Li, Wenlan Liu
Enolase-phosphatase 1 (ENOPH1), a newly discovered enzyme of the methionine salvage pathway, is emerging as an important molecule regulating stress responses. In this study, we investigated the role of ENOPH1 in blood brain barrier (BBB) injury under ischemic conditions. Focal cerebral ischemia induced ENOPH1 mRNA and protein expression in ischemic hemispheric microvessels in rats. Exposure of cultured brain microvascular endothelial cells (bEND3 cells) to oxygen-glucose deprivation (OGD) also induced ENOPH1 upregulation, which was accompanied by increased cell death and apoptosis reflected by increased 3-(4, 5-Dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium bromide formation, lactate dehydrogenase release and TUNEL staining...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27586505/silver-nanoparticles-induce-irremediable-endoplasmic-reticulum-stress-leading-to-unfolded-protein-response-dependent-apoptosis-in-breast-cancer-cells
#12
Jean-Christophe Simard, Isabelle Durocher, Denis Girard
Nowadays, silver nanoparticles (AgNP) are widely used in the medical field mainly for their antibacterial properties. Although some studies report a cytotoxic activity of the particles, the mechanisms involved in AgNP-induced cell death remain to be determined. Herein, we report that AgNP of 2 (AgNP2) and 15 nm (AgNP15) induce apoptosis in human MCF-7 and T-47D breast cancer cells. Treatment with AgNP2 and AgNP15 led to accumulation and aggregation of misfolded proteins causing an endoplasmic reticulum (ER) stress and activating the unfolded protein response (UPR)...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27540856/cysteine-sulfenylation-directs-ire-1-to-activate-the-skn-1-nrf2-antioxidant-response
#13
John M Hourihan, Lorenza E Moronetti Mazzeo, L Paulette Fernández-Cárdenas, T Keith Blackwell
Emerging evidence suggests that many proteins may be regulated through cysteine modification, but the extent and functions of this signaling remain largely unclear. The endoplasmic reticulum (ER) transmembrane protein IRE-1 maintains ER homeostasis by initiating the unfolded protein response (UPR(ER)). Here we show in C. elegans and human cells that IRE-1 has a distinct redox-regulated function in cytoplasmic homeostasis. Reactive oxygen species (ROS) that are generated at the ER or by mitochondria sulfenylate a cysteine within the IRE-1 kinase activation loop...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27538368/reducing-translation-through-eif4g-ifg-1-improves-survival-under-er-stress-that-depends-on-heat-shock-factor-hsf-1-in-caenorhabditis-elegans
#14
Amber C Howard, Jarod Rollins, Santina Snow, Sarah Castor, Aric N Rogers
Although certain methods of lowering and/or altering mRNA translation are associated with increased lifespan, the mechanisms underlying this effect remain largely unknown. We previously showed that the increased lifespan conferred by reducing expression of eukaryotic translation initiation factor 4G (eIF4G/IFG-1) enhances survival under starvation conditions while shifting protein expression toward factors involved with maintaining ER-dependent protein and lipid balance. In this study, we investigated changes in ER homeostasis and found that lower eIF4G/IFG-1 increased survival under conditions of ER stress...
August 18, 2016: Aging Cell
https://www.readbyqxmd.com/read/27537404/mirna-1283-regulates-the-perk-atf4-pathway-in-vascular-injury-by-targeting-atf4
#15
Ling He, Jing Yuan, Qingyun Xu, Ruixue Chen, Liguo Chen, Meixia Fang
BACKGROUND: In our previous study, we found significant differences in the mRNA and microRNA (miRNA) levels among hypertensive patients with different degrees of vascular endothelial cells damage. These differences were closely associated with endoplasmic reticulum stress (ERS)-related proteins. Moreover, compared to the control group, the expression of transcription factor activating factor 4 (ATF4) was also found to be significantly different in the hypertensive patients with different degrees of vascular endothelial cells damage groups...
2016: PloS One
https://www.readbyqxmd.com/read/27499755/unveiling-the-role-of-the-integrated-endoplasmic-reticulum-stress-response-in-leishmania-infection-future-perspectives
#16
K L Dias-Teixeira, R M Pereira, J S Silva, N Fasel, B H Aktas, U G Lopes
The integrated endoplasmic reticulum stress response (IERSR) is an evolutionarily conserved adaptive mechanism that ensures endoplasmic reticulum (ER) homeostasis and cellular survival in the presence of stress including nutrient deprivation, hypoxia, and imbalance of Ca(+) homeostasis, toxins, and microbial infection. Three transmembrane proteins regulate integrated signaling pathways that comprise the IERSR, namely, IRE-1 that activates XBP-1, the pancreatic ER kinase (PERK) that phosphorylates the eukaryotic translation initiation factor 2 and transcription factor 6 (ATF6)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27334229/emerging-roles-of-the-processing-of-nucleic-acids-and-toll-like-receptors-in-innate-immune-responses-to-nucleic-acids
#17
REVIEW
Kensuke Miyake, Takuma Shibata, Umeharu Ohto, Toshiyuki Shimizu
Nucleic acid (NA) is continuously degraded in lysosomes, cytoplasm, and nucleus. NA degradation has a key role in preventing hazardous activation of NA sensors. DNA degradation by lysosomal and cytoplasmic DNases prevents homeostatic activation of cytoplasmic DNA sensing pathways. Crude NA, however, is not sufficient for stimulating NA sensors. mRNAs and rRNAs need to be processed by inositol-requiring enzyme 1 (IRE-1) or RNase L before stimulating cytoplasmic RNA sensors. Activation of cytoplasmic RNA sensors by processed RNAs is tightly controlled by their degradation through the machineries, such as RNA editing, by adenosine (A) deaminases that act on RNA 1 (ADAR1) and the RNA exosome...
January 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27304510/reversible-age-related-phenotypes-induced-during-larval-quiescence-in-c-elegans
#18
Antoine E Roux, Kelley Langhans, Walter Huynh, Cynthia Kenyon
Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding...
June 14, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27221634/4-hydroxybutenolide-impairs-cell-migration-and-invasion-of-human-oral-cancer-scc-4-cells-via-the-inhibition-of-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#19
Fu-Shun Yu, Meng-Liang Lin, Shu-Chun Hsu, Chien-Chih Yu, Yi-Ping Huang, Yueh-Hsiung Kuo, Jing-Gung Chung
4-Hydroxybutenolide (K87), a synthetic compound from furfuryl alcohol via photooxidation, was used to investigate whether it can inhibit mobility, migration and invasion of SCC-4 human oral cancer cells in vitro. Cell viability was measured by flow cytometric assay, the enzymatic activities of MMP-2/9 were assayed by gelatin zymography analysis, the protein levels were assayed by western blotting, confocal laser microscopy and EMSA assay, and the gene expression of MMP-2/-7, FAK and ROCK1 mRNA were assayed by PCR...
August 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27193581/latonduine-analogs-restore-f508del-cystic-fibrosis-transmembrane-conductance-regulator-trafficking-through-the-modulation-of-poly-adp-ribose-polymerase-3-and-poly-adp-ribose-polymerase-16-activity
#20
Graeme W Carlile, Renaud Robert, Elizabeth Matthes, Qi Yang, Roberto Solari, Richard Hatley, Colin M Edge, John W Hanrahan, Raymond Andersen, David Y Thomas, Véronique Birault
Cystic fibrosis (CF) is a major lethal genetic disease caused by mutations in the CF transmembrane conductance regulator gene (CFTR). This encodes a chloride ion channel on the apical surface of epithelial cells. The most common mutation in CFTR (F508del-CFTR) generates a protein that is misfolded and retained in the endoplasmic reticulum. Identifying small molecules that correct this CFTR trafficking defect is a promising approach in CF therapy. However, to date only modest efficacy has been reported for correctors in clinical trials...
August 2016: Molecular Pharmacology
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