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https://www.readbyqxmd.com/read/29045036/endoplasmic-reticulum-stress-regulates-oxygen-glucose-deprivation-induced-parthanatos-in-human-sh-sy5y-cells-via-improvement-of-intracellular-ros
#1
Hai-Feng Wang, Zong-Qi Wang, Ye Ding, Mei-Hua Piao, Chun-Sheng Feng, Guang-Fan Chi, Yi-Nan Luo, Peng-Fei Ge
AIMS: Endoplasmic reticulum (ER) stress has been demonstrated to regulate neuronal death caused by ischemic insults via activation of apoptosis, but it still remains unclear whether ER stress participates in regulation of parthanatos, a new type of programmed cell death characterized by PARP-1 overactivation and intracellular accumulation of PAR polymer. METHODS: we used oxygen-glucose deprivation (OGD) and human SH-SY5Y cells to simulate neuronal damage caused by ischemia...
October 16, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29042437/posttranslational-processing-and-membrane-translocation-of-the-yeast-regulatory-mid1-subunit-of-the-cch1-vgcc-nalcn-cation-channel-family
#2
Kazuko Iida, Jinfeng Teng, Toshihiko Cho, Sato Yoshikawa-Kimura, Hidetoshi Iida
Saccharomyces cerevisiae Mid1 is composed of 548 amino acids and a regulatory subunit of Cch1, a member of the eukaryotic pore-forming, four-domain cation channel family. The amino acid sequence and voltage insensitivity of Cch1 are more similar to those of Na+ leak channel non-selective (NALCN) than to the α1 subunit of voltage-gated Ca2+ channels (VGCCs). Despite a lack in overall primary sequence similarity, Mid1 resembles in some aspects VGCC α2/δ regulatory subunits and NALCN-associated proteins. Unlike animal α2/δ subunits, Mid1 and NALCN-associated proteins are essential for the function of the pore-forming subunit...
October 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29038295/characterization-of-aromatic-residue-controlled-protein-retention-in-the-endoplasmic-reticulum-of-saccharomyces-cerevisiae
#3
Meng Mei, Chao Zhai, Xinzhi Li, Yu Zhou, Wenfang Peng, Lixin Ma, Qinhong Wang, Brent L Iverson, Guimin Zhang, Li Yi
Endoplasmic reticulum (ER) retention sequence (ERS) is a characteristic short sequence that mediates protein retention in the ER of eukaryotic cells. However, little is known about the detailed molecular mechanism involved in ERS-mediated protein ER retention. Using a new surface display-based fluorescence technique that effectively quantifies ERS-promoted protein ER retention within Saccharomyces cerevisiae cells, we performed comprehensive ERS analyses. It was found that the length, type of amino acid residue, and additional residues at position -5 and -6 of C-terminal HDEL motif all determined the retention of ERS in the yeast ER...
October 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28981117/trehalose-ameliorates-oxidative-stress-mediated-mitochondrial-dysfunction-and-er-stress-via-selective-autophagy-stimulation-and-autophagic-flux-restoration-in-osteoarthritis-development
#4
Qian Tang, Gang Zheng, Zhenhua Feng, Yu Chen, Yiting Lou, Chenggui Wang, Xiaolei Zhang, Yu Zhang, Huazi Xu, Ping Shang, Haixiao Liu
Oxidative stress-related apoptosis and autophagy play crucial roles in the development of osteoarthritis (OA), a progressive cartilage degenerative disease with multifactorial etiologies. Here, we determined autophagic flux changes and apoptosis in human OA and tert-Butyl hydroperoxide (TBHP)-treated chondrocytes. In addition, we explored the potential protective effects of trehalose, a novel Mammalian Target of Rapamycin (mTOR)-independent autophagic inducer, in TBHP-treated mouse chondrocytes and a destabilized medial meniscus (DMM) mouse OA model...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978049/ros-independent-nrf2-activation-in-prostate-cancer
#5
Ilaria Bellezza, Paolo Scarpelli, Salvatore V Pizzo, Silvia Grottelli, Egidia Costanzi, Alba Minelli
In prostate cancer, oxidative stress and the subsequent Nrf2 activation promote the survival of cancer cells and acquired chemoresistance. Nrf2 links prostate cancer to endoplasmic reticulum stress, an event that triggers the unfolded protein response, aiming to restore cellular homeostasis as well as an adaptive survival mechanism. Glucose-regulated protein of 78 kD /immunoglobulin heavy chain binding protein (GRP78/BiP) is a key molecular chaperone in the endoplasmic reticulum that, when expressed at the cell surface, acts as a receptor for several signaling pathways enhancing antiapoptotic and proliferative signals...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28978042/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#6
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus. In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975041/escherichia-coli-o157-h7-suppresses-host-autophagy-and-promotes-epithelial-adhesion-via-tir-mediated-and-camp-independent-activation-of-protein-kinase-a
#7
Yansong Xue, Min Du, Haiqing Sheng, Carolyn J Hovde, Mei-Jun Zhu
Autophagy is a pivotal innate immune response that not only degrades cytosolic components, but also serves as one of the critical antimicrobial mechanisms eliminating intracellular pathogens. However, its role in host defense against extracellular pathogens is largely unknown. Here we showed that E. coli O157:H7 altered autophagy to evade host defense and facilitate adhesion. Enhancing host cell autophagy with tumor necrosis factor (TNF), host starvation or rapamycin reduced the adherence of E. coli O157:H7 to HT-29 cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28970512/multiple-regulatory-mechanisms-of-the-biological-function-of-nrf3-nfe2l3-control-cancer-cell-proliferation
#8
A M Masudul Azad Chowdhury, Hiroki Katoh, Atsushi Hatanaka, Hiroko Iwanari, Nanami Nakamura, Takao Hamakubo, Tohru Natsume, Tsuyoshi Waku, Akira Kobayashi
Accumulated evidence suggests a physiological relationship between the transcription factor NRF3 (NFE2L3) and cancers. Under physiological conditions, NRF3 is repressed by its endoplasmic reticulum (ER) sequestration. In response to unidentified signals, NRF3 enters the nucleus and modulates gene expression. However, molecular mechanisms underlying the nuclear translocation of NRF3 and its target gene in cancer cells remain poorly understood. We herein report that multiple regulation of NRF3 activities controls cell proliferation...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962875/tat-proteins-as-novel-thylakoid-membrane-anchors-organize-a-biosynthetic-pathway-in-chloroplasts-and-increase-product-yield-5-fold
#9
Maria Perestrello Ramos Henriques de Jesus, Agnieszka Zygadlo Nielsen, Silas Busck Mellor, Annemarie Matthes, Meike Burow, Colin Robinson, Poul Erik Jensen
Photosynthesis drives the production of ATP and NADPH, and acts as a source of carbon for primary metabolism. NADPH is also used in the production of many natural bioactive compounds. These are usually synthesized in low quantities and are often difficult to produce by chemical synthesis due to their complex structures. Some of the crucial enzymes catalyzing their biosynthesis are the cytochromes P450 (P450s) situated in the endoplasmic reticulum (ER), powered by electron transfers from NADPH. Dhurrin is a cyanogenic glucoside and its biosynthesis involves a dynamic metabolon formed by two P450s, a UDP-glucosyltransferase (UGT) and a P450 oxidoreductase (POR)...
September 28, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28960134/differential-requirement-of-rab22a-for-the-recruitment-of-er-derived-proteins-to-phagosomes-and-endosomes-in-dendritic-cells
#10
Cristina Croce, Luis S Mayorga, Ignacio Cebrian
The recruitment of endoplasmic reticulum (ER) components to dendritic cell (DC) phagosomes and endosomes is a crucial event to achieve efficient cross-presentation of exogenous antigens. We have previously identified the small GTPase Rab22a as a key regulator of MHC-I trafficking and antigen cross-presentation by DCs. In this study we show that low expression of Rab22a does not prevent the normal delivery of ER-derived proteins to DC phagosomes. In contrast, the presence of these proteins was diminished in endosomes labelled with a fluid phase marker...
September 29, 2017: Small GTPases
https://www.readbyqxmd.com/read/28959426/optical-control-of-membrane-tethering-and-interorganellar-communication-at-nanoscales
#11
Lian He, Ji Jing, Lei Zhu, Peng Tan, Guolin Ma, Qian Zhang, Nhung T Nguyen, Junfeng Wang, Yubin Zhou, Yun Huang
Endoplasmic reticulum (ER) forms an extensive intracellular membranous network in eukaryotes that dynamically connects and communicates with diverse subcellular compartments such as plasma membrane (PM) through membrane contact sites (MCSs), with the inter-membrane gaps separated by a distance of 10-40 nm. Phosphoinositides (PI) constitute an important class of cell membrane phospholipids shared by many MCSs to regulate a myriad of cellular events, including membrane trafficking, calcium homeostasis and lipid metabolism...
August 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28955770/pentylenetetrazol-modulates-redox-system-by-inducing-addicsin-translocation-from-endoplasmic-reticulum-to-plasma-membrane-in-ng108-15-cells
#12
Mitsushi J Ikemoto, Yusuke Murasawa, Pi-Chao Wang
Addicsin (Arl6ip5) is a multifunctional physiological and pathophysiological regulator that exerts its effects by readily forming homo- and hetero-complexes with various functional factors. In particular, addicsin acts as a negative modulator of neural glutamate transporter excitatory amino acid carrier 1 (EAAC1) and participates in the regulation of intracellular glutathione (GSH) content by negatively modulating EAAC1-mediated cysteine and glutamate uptake. Addicsin is considered to play a crucial role in the onset of neurodegenerative diseases including epilepsy...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28954889/herp-binds-tbk1-to-activate-innate-immunity-and-repress-virus-replication-in-response-to-endoplasmic-reticulum-stress
#13
Maolin Ge, Zhen Luo, Zhi Qiao, Yao Zhou, Xin Cheng, Qibin Geng, Yanyan Cai, Pin Wan, Ying Xiong, Fang Liu, Kailang Wu, Yingle Liu, Jianguo Wu
Host innate immunity is crucial for cellular responses against viral infection sensed by distinct pattern recognition receptors and endoplasmic reticulum (ER) stress. Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and neurological diseases. However, the exact mechanism underlying the link between ER stress induced by EV71 infection and host innate immunity is largely unknown. In this study, we demonstrated that EV71 infection induces the homocysteine-induced ER protein (HERP), a modulator of the ER stress response which is dependent on the participation of MAVS...
September 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28938588/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#14
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937681/primary-t-cells-for-mrna-mediated-immunotoxin-delivery
#15
R Eggers, A Philippi, M O Altmeyer, F Breinig, M J Schmitt
Immune cells become increasingly attractive as delivery system for immunotoxins in cancer therapy in order to reduce the intrinsic toxicity and severe side effects of chimeric protein toxins. In this study, we investigated the potential of human primary T cells to deliver a secreted immunotoxin through transient mRNA transfection. The chimeric protein toxin was directed towards the neovasculature of cancer cells by fusing a truncated version of Pseudomonas exotoxin A (PE38) to human vascular endothelial growth factor (VEGF) and to the single chain variable fragment (scFv) of anti-Her2/neu...
September 22, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28935573/acrolein-disrupts-tight-junction-proteins-and-causes-endoplasmic-reticulum-stress-mediated-epithelial-cell-death-leading-to-intestinal-barrier-dysfunction-and-permeability
#16
Wei-Yang Chen, Min Wang, Jingwen Zhang, Shirish S Barve, Craig J McClain, Swati Joshi-Barve
Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood...
September 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28931913/cell-free-synthesis-of-functional-antibodies-using-a-coupled-in-vitro-transcription-translation-system-based-on-cho-cell-lysates
#17
M Stech, O Nikolaeva, L Thoring, W F M Stöcklein, D A Wüstenhagen, M Hust, S Dübel, S Kubick
Antibodies are indispensable tools for basic research as well as diagnostic and therapeutic applications. Consequently, the development of alternative manufacturing strategies which circumvent the hurdles connected to conventional antibody production technologies is of enormous interest. To address this issue, we demonstrate the synthesis of complex antibody formats, in particular immunoglobulin G (IgG) and single-chain variable fragment Fc fusion (scFv-Fc), in a microsome-containing cell-free system based on translationally active chinese hamster ovary (CHO) cell lysates...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928762/novel-protein-protein-inhibitor-based-approach-to-control-plant-ethylene-responses-synthetic-peptides-for-ripening-control
#18
Mareike Kessenbrock, Simone M Klein, Lena Müller, Mauricio Hunsche, Georg Noga, Georg Groth
Ethylene signaling is decisive for many plant developmental processes. Among these, control of senescence, abscission and fruit ripening are of fundamental relevance for global agriculture. Consequently, detailed knowledge of the signaling network along with the molecular processes of signal perception and transfer are expected to have high impact on future food production and agriculture. Recent advances in ethylene research have demonstrated that signaling of the plant hormone critically depends on the interaction of the ethylene receptor family with the NRAMP-like membrane protein ETHYLENE INSENSITIVE 2 (EIN2) at the ER membrane, phosphorylation-dependent proteolytic processing of ER-localized EIN2 and subsequent translocation of the cleaved EIN2 C-terminal polypeptide (EIN2-CEND) to the nucleus...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28926118/chop-induced-loss-of-intestinal-epithelial-stemness-contributes-to-bile-duct-ligation-induced-cholestatic-liver-injury
#19
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/28924045/interaction-between-repressor-opi1p-and-er-membrane-protein-scs2p-facilitates-transit-of-phosphatidic-acid-from-the-er-to-mitochondria-and-is-essential-for-ino1-gene-expression-in-the-presence-of-choline
#20
Maria L Gaspar, Yu-Fang Chang, Stephen A Jesch, Manuel Aregullin, Susan A Henry
In the yeast Saccharomyces cerevisiae, the Opi1p repressor controls the expression of INO1 via the Opi1p/Ino2p-Ino4p regulatory circuit. Inositol depletion favors Opi1p interaction with both Scs2p and phosphatidic acid at the ER membrane. Inositol supplementation, however, favors the translocation of Opi1p from the ER into the nucleus where it interacts with the Ino2p-Ino4p complex, attenuating transcription of INO1. A strain devoid of Scs2p (scs2) and a mutant, OPI1FFAT, lacking the ability to interact with Scs2p were utilized to examine the specific role(s) of the Opi1p-Scs2p interaction in the regulation of INO1 expression and overall lipid metabolism...
September 18, 2017: Journal of Biological Chemistry
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