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https://www.readbyqxmd.com/read/28075361/role-of-ire1%C3%AE-xbp-1-in-cystic-fibrosis-airway-inflammation
#1
REVIEW
Carla M P Ribeiro, Bob A Lubamba
Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes...
January 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28074539/ritterostatin-gn1n-a-cephalostatin-ritterazine-bis-steroidal-pyrazine-hybrid-selectively-targets-grp78
#2
Andrew J Ambrose, Evelyne A Santos, Paula C Jimenez, Danilo D Rocha, Diego V Wilke, Paolo Beuzer, Josh Axelrod, Ananda Kumar Kanduluru, Philip L Fuchs, Hu Cang, Letícia V Costa-Lotufo, Eli Chapman, James J La Clair
Natural products discovered using agnostic approaches, unlike rationally designed or HTS obtained leads, offer the ability to reveal new biological pathways, and hence, serve as an important vehicle to unveil new avenues in drug discovery. The ritterazine-cephalostatin family of natural products displays robust and potent anti-tumor activities, with sub-nanomolar growth inhibition against multiple cell lines and potent activity in xenograft models. Herein, we use comparative cellular and molecular biological methods to uncover the ritterazine/cephalostatin mode of cytotoxic action (MOA) in human tumor cells...
January 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28073911/a-truncated-g-csfr-inhibits-apoptosis-induced-by-neutrophil-elastase-g185r-mutant-implication-for-understanding-csf3r-mutations-in-severe-congenital-neutropenia
#3
Yaling Qiu, Yangyang Zhang, Nan Hu, Fan Dong
Mutations in ELANE encoding neutrophil elastase (NE) have been identified in the majority of patients with severe congenital neutropenia (SCN). The NE mutants have been shown to activate unfolded protein response (UPR) and induce premature apoptosis in myeloid cells. Patients with SCN are predisposed to acute myeloid leukemia (AML), and progression from SCN to AML is accompanied by mutations in CSF3R encoding the G-CSF receptor (G-CSFR) in approximately 80% patients. The mutations result in the expression of C-terminally truncated G-CSFRs that promote strong cell proliferation and survival...
January 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28070992/molecular-signal-networks-and-regulating-mechanisms-of-the-unfolded-protein-response
#4
Jing Gong, Xing-Zhi Wang, Tao Wang, Jiao-Jiao Chen, Xiao-Yuan Xie, Hui Hu, Fang Yu, Hui-Lin Liu, Xing-Yan Jiang, Han-Dong Fan
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum (ER). One of the primary mechanisms is the unfolded protein response (UPR). In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein (BiP) interacts with the three sensors (protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme 1α (IRE1α))...
2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28070110/melatonin-suppresses-methamphetamine-triggered-endoplasmic-reticulum-stress-in-c6-cells-glioma-cell-lines
#5
Wanida Tungkum, Pichaya Jumnongprakhon, Chainarong Tocharus, Piyarat Govitrapong, Jiraporn Tocharus
Methamphetamine (METH) is a neurotoxic drug that causes brain damage by inducing neuronal and glial cell death together with glial cell hyperactivity-mediated progressive neurodegeneration. Previous studies have shown that METH induced glial cell hyperactivity and death via oxidative stress, the inflammatory response, and endoplasmic reticulum stress (ER stress) mechanisms, and melatonin could reverse these effects. However, the exact mechanism of the protective role of melatonin in METH-mediated ER stress has not been understood...
2017: Journal of Toxicological Sciences
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
#6
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/28064367/cellular-responses-to-the-expression-of-unstable-secretory-proteins-in-the-filamentous-fungus-aspergillus-oryzae
#7
Jun-Ichi Yokota, Daisuke Shiro, Mizuki Tanaka, Yasumichi Onozaki, Osamu Mizutani, Dararat Kakizono, Sakurako Ichinose, Tomoko Shintani, Katsuya Gomi, Takahiro Shintani
Filamentous fungi are often used as cell factories for recombinant protein production because of their ability to secrete large quantities of hydrolytic enzymes. However, even using strong transcriptional promoters, yields of nonfungal proteins are generally much lower than those of fungal proteins. Recent analyses revealed that expression of certain nonfungal secretory proteins induced the unfolded protein response (UPR), suggesting that they are recognized as proteins with folding defects in filamentous fungi...
January 7, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28057903/reactive-oxygen-species-mediated-unfolded-protein-response-pathways-in-pre-implantation-embryo
#8
REVIEW
Ihsan Ali, Syed Zahid Ali Shah, Jin Yi, Li Zhong-Shu, Obaidullah, Fang Nan-Zhu
The excessive production of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress mediated responses are critical to embryonic development in the challenging in-vitro environment. ROS production increases during early embryonic development with the increased protein requirement for cell survival and growth. The endoplasmic reticulum (ER) is a multifunctional cellular organelle responsible for protein folding, modification, and cellular homeostasis. ER stress is activated by a variety of factors including ROS, leading to activation of the adaptive unfolded protein response (UPR), which restores homeostasis...
January 4, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28039913/the-unfolded-protein-response-mediates-fibrogenesis-and-collagen-i-secretion-through-regulating-tango1-in-mice
#9
Jessica L Maiers, Enis Kostallari, Malek Mushref, Thiago M deAssuncao, Haiyang Li, Nidhi Jalan-Sakrikar, Robert C Huebert, Sheng Cao, Harmeet Malhi, Vijay H Shah
: Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28039491/sodium-fluoride-naf-induces-the-splenic-apoptosis-via-endoplasmic-reticulum-er-stress-pathway-in-vivo-and-in-vitro
#10
Huidan Deng, Ping Kuang, Hengmin Cui, Lian Chen, Qin Luo, Jing Fang, Zhicai Zuo, Junliang Deng, Xun Wang, Ling Zhao
At present, there are no reports on the relationship between fluoride-induced apoptosis and endoplasmic reticulum (ER) stress (ER stress) in the spleen of human and animals in vivo and in vitro. Therefore, the aim of this study was to define sodium fluoride (NaF)-induced apoptosis mediated by ER stress in the spleen of mice in vivo and in vitro. Apoptosis and expression levels of the ER stress-related proteins were detected by flow cytometry and western blot, respectively. The results showed that NaF treatment increased lymphocytes apoptosis, which was consistent with NaF-caused ER Stress...
December 27, 2016: Aging
https://www.readbyqxmd.com/read/28039489/trail-receptor-gene-editing-unveils-trail-r1-as-a-master-player-of-apoptosis-induced-by-trail-and-er-stress
#11
Florent Dufour, Thibault Rattier, Andrei Alexandru Constantinescu, Luciana Zischler, Aymeric Morlé, Hazem Ben Mabrouk, Etienne Humblin, Guillaume Jacquemin, Eva Szegezdi, Fabien Delacote, Naziha Marrakchi, Gilles Guichard, Catherine Pellat-Deceunynk, Pierre Vacher, Patrick Legembre, Carmen Garrido, Olivier Micheau
TRAIL induces selective tumor cell death through TRAIL-R1 and TRAIL-R2. Despite the fact that these receptors share high structural homologies, induction of apoptosis upon ER stress, cell autonomous motility and invasion have solely been described to occur through TRAIL-R2. Using the TALEN gene-editing approach, we show that TRAIL-R1 can also induce apoptosis during unresolved unfolded protein response (UPR). Likewise, TRAIL-R1 was found to co-immunoprecipitate with FADD and caspase-8 during ER stress. Its deficiency conferred resistance to apoptosis induced by thaspigargin, tunicamycin or brefeldin A...
27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039331/hepatic-deletion-of-x-box-binding-protein-1-impairs-bile-acid-metabolism-in-mice
#12
Xiaoying Liu, Anne S Henkel, Brian E LeCuyer, Susan C Hubchak, Matthew J Schipma, Eric Zhang, Richard M Green
The unfolded protein response (UPR) is an adaptive response to endoplasmic reticulum stress and the inositol-requiring enzyme 1α/X-box binding protein 1 (IRE1α/XBP1) pathway of the UPR is important in lipid metabolism. However, its role in bile acid metabolism remains unknown. We demonstrate that liver-specific Xbp1 knockout (LS-Xbp1(-/-)) mice had a 45% reduction in total bile acid pool. LS-Xbp1(-/-) mice had lower serum 7α-hydroxy-4-cholesten-3-one (C4) levels compared to Xbp1(fl/fl) mice, indicating reduced CYP7A1 synthetic activity...
December 30, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/28038917/a-positive-feedback-loop-between-grp78-and-vps34-is-critical-for-grp78-mediated-autophagy-in-cancer-cells
#13
Yingying Wang, Haili Wu, Zongwei Li, Peng Yang, Zhuoyu Li
Autophagy and GRP78 overexpression are two important means by which tumor cells resist microenvironmental stress and chemotherapeutic drugs; however, the relationship between autophagy and GRP78 remains unclear. Here, we found that forced expression of GRP78 in tumor cells promoted autophagy, which was indicated by alterations in the levels of autophagy related proteins, such as increased VPS34 and LC3-II, and decreased p62 and LC3-I. Consistently, GRP78 knockdown suppressed tumor cell autophagy. Our results further demonstrated that GRP78-induced autophagy was mediated by VPS34, and that UPR-associated autophagy was also involved...
December 27, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28032645/arabidopsis-b-cell-lymphoma2-bcl-2-associated-athanogene-7-bag7-mediated-heat-tolerance-requires-translocation-sumoylation-and-binding-to-wrky29
#14
Yurong Li, Brett Williams, Martin Dickman
To cope with stress and increased accumulation of misfolded proteins, plants and animals use a survival pathway known as the unfolded protein response (UPR) that signals between the endoplasmic reticulum (ER) and the nucleus to maintain cell homeostasis via proper folding of proteins. B-cell lymphoma2 (Bcl-2)-associated athanogene (BAG) proteins are an evolutionarily conserved family of co-chaperones that are linked to disease states in mammals and responses to environmental stimuli (biotic and abiotic) in plants...
December 29, 2016: New Phytologist
https://www.readbyqxmd.com/read/28029795/spoxazomicin-d-and-oxachelin-c-potent-neuroprotective-carboxamides-from-the-appalachian-coal-fire-associated-isolate-streptomyces-sp-rm-14-6
#15
Khaled A Shaaban, Meredith A Saunders, Yinan Zhang, Tuan Tran, Sherif I Elshahawi, Larissa V Ponomareva, Xiachang Wang, Jianjun Zhang, Gregory C Copley, Manjula Sunkara, Madan K Kharel, Andrew J Morris, James C Hower, Matthew S Tremblay, Mark A Prendergast, Jon S Thorson
The isolation and structure elucidation of six new bacterial metabolites [spoxazomicin D (2), oxachelins B and C (4, 5), and carboxamides 6-8] and 11 previously reported bacterial metabolites (1, 3, 9-12a, and 14-18) from Streptomyces sp. RM-14-6 is reported. Structures were elucidated on the basis of comprehensive 1D and 2D NMR and mass spectrometry data analysis, along with direct comparison to synthetic standards for 2, 11, and 12a,b. Complete 2D NMR assignments for the known metabolites lenoremycin (9) and lenoremycin sodium salt (10) were also provided for the first time...
December 28, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/28029742/functional-interaction-of-erap2-and-hla-b27-activates-the-unfolded-protein-response
#16
Zhenbo Zhang, Francesco Ciccia, Fanxing Zeng, Giuliana Guggino, Kirby Yee, Hasan Abdullah, Mark S Silverberg, Riccardo Alessandro, Giovanni Triolo, Nigil Haroon
OBJECTIVES: The basic mechanisms underlying ankylosing spondylitis (AS) pathogenesis remain unresolved. We previously reported an association of the single nucleotide polymorphisms (SNP) rs2549782 in Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with AS. It is known that patients homozygous for the G allele (GG) of another ERAP2 SNP rs2248374 have no ERAP2 expression (ERAP2-null). We utilized this information to study the impact of ERAP2 deficiency on HLA-B27 expression in AS patients...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28029379/characterization-of-nuclear-foci-targeting-of-luman-creb3-recruitment-factor-lrf-crebrf-and-its-potential-role-in-inhibition-of-herpes-simplex-virus-1-replication
#17
Timothy E Audas, Philip W Hardy-Smith, Jenna Penney, Tiegh Taylor, Ray Lu
The recently identified Luman/CREB3-binding partner LRF (Luman/CREB3 recruitment factor) was shown to localize to discrete sub-nuclear foci. Luman is implicated in herpes simplex virus-1 (HSV-1) latency/reactivation and the unfolded protein response (UPR) pathway; therefore, we sought to characterize the formation of the LRF nuclear foci in the context of cellular signaling and HSV-1 replication. Here, we mapped the nuclear foci-targeting sequence to the central region containing the first leucine zipper (a...
October 26, 2016: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28017918/effects-of-ketamine-administration-on-mtor-and-reticulum-stress-signaling-pathways-in-the-brain-after-the-infusion-of-rapamycin-into-prefrontal-cortex
#18
Helena M Abelaira, Gislaine Z Réus, Zuleide M Ignácio, Maria Augusta B Dos Santos, Airam B de Moura, Danyela Matos, Júlia P Demo, Júlia B I da Silva, Monique Michels, Mariane Abatti, Beatriz Sonai, Felipe Dal Pizzol, André F Carvalho, João Quevedo
Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC...
December 3, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28011957/effect-of-pulsed-electromagnetic-fields-on-endoplasmic-reticulum-stress
#19
E Keczan, G Keri, G Banhegyi, I Stiller
The maintenance of protein homeostasis in the endoplasmic reticulum (ER) is crucial in cell life. Disruption of proteostasis results in ER stress that activates the unfolded protein response (UPR); a signalling network assigned to manage the accumulated misfolded or unfolded proteins. Prolonged or unresolved ER stress leads to apoptotic cell death that can be the basis of many serious diseases. Our aim was to study the effect of pulsed electromagnetic fields (PEMF), an alternative, non-invasive therapeutic method on ER stressed cell lines...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28004277/tauroursodeoxycholic-bile-acid-arrests-axonal-degeneration-by-inhibiting-the-unfolded-protein-response-in-x-linked-adrenoleukodystrophy
#20
Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme...
December 21, 2016: Acta Neuropathologica
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