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https://www.readbyqxmd.com/read/28431320/trehalose-supplementation-reduces-hepatic-endoplasmic-reticulum-stress-and-inflammatory-signaling-in-old-mice
#1
Michael J Pagliassotti, Andrea L Estrada, William M Hudson, Yuren Wei, Dong Wang, Douglas R Seals, Melanie L Zigler, Thomas J LaRocca
The accumulation of damaged proteins can perturb cellular homeostasis and provoke aging and cellular damage. Quality control systems, such as the unfolded protein response (UPR), inflammatory signaling and protein degradation, mitigate the residence time of damaged proteins. In the present study, we have examined the UPR and inflammatory signaling in the liver of young (~6 months) and old (~28 months) mice (n=8/group), and the ability of trehalose, a compound linked to increased protein stability and autophagy, to counteract age-induced effects on these systems...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28429799/expression-control-of-the-ampk-regulatory-subunit-and-its-functional-significance-in-yeast-er-stress-response
#2
Yuichi Kimura, Kenji Irie, Tomoaki Mizuno
AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimeric kinase complex consisting of a catalytic subunit, α, and two regulatory subunits, β and γ. Previously, we demonstrated that Snf1, the Saccharomyces cerevisiae ortholog of AMPK, negatively regulates the unfolded protein response (UPR) pathway and the Hog1 MAP kinase pathway in ER stress response. However, it remains unclear how the alternate three β subunits, Sip1, Sip2, and Gal83, of the Snf1 complex participate in ER stress response...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428045/sco2-deficient-mice-develop-increased-adiposity-and-insulin-resistance
#3
Shauna Hill, Sathyaseelan S Deepa, Kavithalakshmi Sataranatarajan, Pavithra Premkumar, Daniel Pulliam, Yuhong Liu, Vanessa Y Soto, Kathleen E Fischer, Holly Van Remmen
Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex IV) in the mitochondrial respiratory electron chain. Mutations in genes responsible for the assembly of COX are associated with Leigh syndrome, cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in humans. Previous studies have shown that mice lacking the COX assembly protein Surf1 (Surf1(-/-) mice) paradoxically show a number of beneficial metabolic phenotypes including increased insulin sensitivity, upregulation of mitochondrial biogenesis, induction of stress response pathways and increased lifespan...
April 17, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28424579/grp78-at-the-centre-of-the-stage-in-cancer-and-neuroprotection
#4
REVIEW
Caty Casas
The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28424159/prolonged-elimination-of-negative-feedback-control-mechanisms-along-the-insulin-signalling-pathway-impairs-%C3%AE-cell-function-in-vivo
#5
Roi Isaac, Yaron Vinik, Sigalit Boura-Halfon, Lydia Farack, Sarina Streim, Eytan Elhanany, Zvi Kam, Yehiel Zick
Cellular stress and pro-inflammatory cytokines induce phosphorylation of insulin receptor substrate (IRS) proteins at Ser sites that inhibit insulin and IGF-1 signalling. We therefore examined the effects of mutation of five 'inhibitory' Ser phosphorylation sites on IRS2 function in transgenic mice that overexpress, selectively in pancreatic β cells, either wild-type (WT) or a mutated IRS2 protein (IRS2(5A)). Islets size, number, and mRNA levels of catalase and superoxide dismutase, were increased, while those of nitric oxide synthase were decreased in 7-10 weeks old IRS2(5A)-β mice compared to IRS2(WT)-β mice...
April 19, 2017: Diabetes
https://www.readbyqxmd.com/read/28423644/disulfide-bond-disrupting-agents-activate-the-unfolded-protein-response-in-egfr-and-her2-positive-breast-tumor-cells
#6
Renan B Ferreira, Mengxiong Wang, Mary E Law, Bradley J Davis, Ashton N Bartley, Paul J Higgins, Michael S Kilberg, Katherine E Santostefano, Naohiro Terada, Coy D Heldermon, Ronald K Castellano, Brian K Law
Many breast cancer deaths result from tumors acquiring resistance to available therapies. Thus, new therapeutic agents are needed for targeting drug-resistant breast cancers. Drug-refractory breast cancers include HER2+ tumors that have acquired resistance to HER2-targeted antibodies and kinase inhibitors, and "Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR)...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423496/mtor-inhibitors-activate-perk-signaling-and-favor-viability-of-gastrointestinal-neuroendocrine-cell-lines
#7
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/28420736/deciphering-the-regulatory-network-between-the-srebp-pathway-and-protein-secretion-in-neurospora-crassa
#8
Lina Qin, Vincent W Wu, N Louise Glass
Sterol regulatory element binding proteins (SREBPs) are conserved from yeast to mammalian cells and function in the regulation of sterol homeostasis. In fungi, the SREBP pathway has been implicated in the adaptation to hypoxia and in virulence. In Neurospora crassa and Trichoderma reesei, the SREBP pathway also negatively regulates protein secretion under lignocellulolytic conditions. Here we utilized global transcriptional profiling combined with genetic and physiological analyses to address the regulatory link between the SREBP pathway and protein secretion in N...
April 18, 2017: MBio
https://www.readbyqxmd.com/read/28420170/fisetin-protects-pc12-cells-from-tunicamycin-mediated-cell-death-via-reactive-oxygen-species-scavenging-and-modulation-of-nrf2-driven-gene-expression-sirt1-and-mapk-signaling-in-pc12-cells
#9
Jui-Hung Yen, Pei-Shan Wu, Shu-Fen Chen, Ming-Jiuan Wu
BACKGROUND: Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonol and exhibits antioxidant, anti-inflammatory, and neuroprotective activities. However, high concentration of fisetin is reported to produce reactive oxygen species (ROS), induce endoplasmic reticulum (ER) stress and cause cytotoxicity in cancer cells. The aim of this study is to investigate the cytoprotective effects of low concentration of fisetin against tunicamycin (Tm)-mediated cytotoxicity in neuronal-like catecholaminergic PC12 cells...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418178/unfolded-protein-response-activation-compensates-er-associated-degradation-deficiency-in-arabidopsis
#10
Qingliang Li, Hai Wei, Lijing Liu, Xiaoyuan Yang, Xiansheng Zhang, Qi Xie
Abiotic stresses often disrupt protein folding and induce endoplasmic reticulum (ER) stress. There is a sophisticated ER quality control (ERQC) system to mitigate the effects of malfunctioning proteins and maintain ER homeostasis. The accumulation of misfolded proteins in the ER activates the unfolded protein response (UPR) to enhance ER protein folding and the degradation of misfolded proteins mediate by ER-associated degradation (ERAD). That ERQC reduces abiotic stress damage has been well studied in mammals and yeast...
April 18, 2017: Journal of Integrative Plant Biology
https://www.readbyqxmd.com/read/28416388/human-grp78-affinity-towards-its-signaling-partners-ire1%C3%AE-and-perk-is-differently-modulated-by-an-unfolded-protein-client
#11
Razvan C Stan, Raissa L Silva, Maristela M de Camargo
Protein-folding stress is characteristic of specialized secretory cells and plays a dominant role in a multitude of diseases. The unfolded protein response (UPR) thus triggered is a proteostatic signaling network that adapts the protein-folding capacity of the endoplasmic reticulum to the cellular demands. We have measured the binding affinities between human GRP78, an essential chaperone located in ER, and two transmembrane UPR sensors (human PERK and Ire1α), with or without the addition of an unfolded protein client...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28415683/suppression-of-pkc-causes-oncogenic-stress-for-triggering-apoptosis-in-cancer-cells
#12
Suthakar Ganapathy, Bo Peng, Ling Shen, Tianqi Yu, Jean Lafontant, Ping Li, Rui Xiong, Alexandros Makriyannis, Changyan Chen
Gain of functional mutations in ras occurs in more than 30% of human malignancies and in particular 90% of pancreatic cancer. Mutant ras, via activating multiple effector pathways, not only promote cell growth or survival, but also apoptosis, depending upon cell types or circumstances. In order to further study the mechanisms of apoptosis induced by oncogenic ras, we employed the ras loop mutant genes and demonstrated that Akt functioned downstream of Ras in human pancreatic cancer or HPNE cells ectopically expressing mutated K-ras for the induction of apoptosis after the concurrent suppression of PKC α and β...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414129/the-arabidopsis-endoplasmic-reticulum-associated-degradation-pathways-are-involved-in-the-regulation-of-heat-stress-response
#13
Lin-Mao Li, Shi-You Lü, Rong-Jun Li
The Cytosolic Protein Response (CPR) in the cytosol and the Unfolded Protein Response (UPR) and ER-associated degradation (ERAD) in the endoplasmic reticulum are major pathways of the cellular proteostasis network. However, despite years of effort, how these protein quality control systems coordinated in vivo remains largely unknown, particularly in plants. In this study, the roles of two evolutionarily conserved ERAD pathways (DOA10 and HRD1) in heat stress response were investigated through reverse genetic approaches in Arabidopsis...
April 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28412728/increased-reactive-oxygen-species-levels-cause-er-stress-and-cytotoxicity-in-andrographolide-treated-colon-cancer-cells
#14
Aditi Banerjee, Vivekjyoti Banerjee, Steven Czinn, Thomas Blanchard
Chemotherapy continues to play an essential role in the management of many cancers including colon cancer, the third leading cause of death due to cancer in the United States. Many naturally occurring plant compounds have been demonstrated to possess anti-cancer cell activity and have the potential to supplement existing chemotherapy strategies. The plant metabolite andrographolide induces cell death in cancer cells and apoptosis is dependent upon the induction of endoplasmic reticulum stress (ER stress) leading to the unfolded protein response (UPR)...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407373/activation-of-the-arabidopsis-membrane-bound-transcription-factor-bzip28-is-mediated-by-site-2-protease-but-not-site-1-protease
#15
Yuji Iwata, Makoto Ashida, Chisa Hasegawa, Kazuki Tabara, Kei-Ichiro Mishiba, Nozomu Koizumi
The unfolded protein response (UPR) is a homeostatic cellular response conserved in eukaryotic cells to alleviate the accumulation of unfolded proteins in the endoplasmic reticulum (ER). Arabidopsis bZIP28 is a membrane-bound transcription factor activated by proteolytic cleavage in response to ER stress, thereby releasing its cytosolic portion containing the bZIP domain from the membrane to translocate into the nucleus where it induces the transcription of genes encoding ER-resident molecular chaperones and folding enzymes...
April 13, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28403212/longitudinal-monitoring-of-gaussia-and-nano-luciferase-activities-to-concurrently-assess-er-calcium-homeostasis-and-er-stress-in-vivo
#16
Emily S Wires, Mark J Henderson, Xiaokang Yan, Susanne Bäck, Kathleen A Trychta, Molly H Lutrey, Brandon K Harvey
The endoplasmic reticulum (ER) is essential to many cellular processes including protein processing, lipid metabolism and calcium storage. The ability to longitudinally monitor ER homeostasis in the same organism would offer insight into progressive molecular and cellular adaptations to physiologic or pathologic states, but has been challenging. We recently described the creation of a Gaussia luciferase (GLuc)-based secreted ER calcium-modulated protein (SERCaMP or GLuc-SERCaMP) to longitudinally monitor ER calcium homeostasis...
2017: PloS One
https://www.readbyqxmd.com/read/28397763/endoplasmic-reticulum-stress-and-homeostasis-in-reproductive-physiology-and-pathology
#17
REVIEW
Elif Guzel, Sefa Arlier, Ozlem Guzeloglu-Kayisli, Mehmet Selcuk Tabak, Tugba Ekiz, Nihan Semerci, Kellie Larsen, Frederick Schatz, Charles Joseph Lockwood, Umit Ali Kayisli
The endoplasmic reticulum (ER), comprises 60% of the total cell membrane and interacts directly or indirectly with several cell organelles i.e., Golgi bodies, mitochondria and proteasomes. The ER is usually associated with large numbers of attached ribosomes. During evolution, ER developed as the specific cellular site of synthesis, folding, modification and trafficking of secretory and cell-surface proteins. The ER is also the major intracellular calcium storage compartment that maintains cellular calcium homeostasis...
April 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28396092/targeting-the-unfolded-protein-response-in-cancer
#18
REVIEW
Rani Ojha, Ravi K Amaravadi
Cancer cells are exposed to various intrinsic and extrinsic factors that disrupt protein homeostasis, producing endoplasmic reticulum (ER) stress. To cope with these situations, cancer cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR) to restore the ER homeostasis. Recently, several pharmacological agents have been found to exhibit anti-tumor activity by targeting the UPR components. The development of potent and specific compounds that target the UPR components has not only shed light on the regulation of the UPR in cancer cells, but also brought the field closer to clinical drug candidates...
April 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28390949/ncls-and-er-a-stressful-relationship
#19
REVIEW
Davide Marotta, Elisa Tinelli, Sara E Mole
The Neuronal Ceroid Lipofuscinoses (NCLs, Batten disease) are a group of inherited neurodegenerative disorders with variable age of onset, characterised by the lysosomal accumulation of autofluorescent ceroid lipopigments. The endoplasmic reticulum (ER) is a critical organelle for normal cell function. Alteration of ER homeostasis leads to accumulation of misfolded protein in the ER and to activation of the unfolded protein response. ER stress and the UPR have recently been linked to the NCLs. In this review, we will discuss the evidence for UPR activation in the NCLs, and address its connection to disease pathogenesis...
April 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28384556/effect-of-cuprous-oxide-with-different-sizes-on-thermal-and-combustion-behaviors-of-unsaturated-polyester-resin
#20
Yanbei Hou, Weizhao Hu, Zhou Gui, Yuan Hu
Cuprous oxide (Cu2O) as an effective catalyst has been applied to enhance the fire safety of unsaturated polyester resin (UPR), but the particle size influence on combustion behaviors has not been previously reported. Herein, the UPR/Cu2O composites (metal oxide particles with average particle-size of 10, 100, and 200nm) were successfully synthesized by thermosetting process. The effects of Cu2O with different sizes on thermostability and combustion behaviors of UPR were characterized by TGA, MCC, TG-IR, FTIR, and SSTF...
March 27, 2017: Journal of Hazardous Materials
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