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unfolded protein response

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https://www.readbyqxmd.com/read/29150287/anastasis-and-the-er-stress-response-solving-the-paradox-of-the-unfolded-protein-response-in-cancer
#1
Rafael Vincent M Manalo
In recent years, studies have suggested a novel pathway for cell survival, which faces scientific skepticism and interest in its concept of cell 'resurrection' - that is, the anastasis of cells at late-stage apoptosis. While biomarkers have been discovered, many of these are related to the endoplasmic reticulum (ER) stress response - acting also to promote cell survival in the presence of perturbation. The promises of anastasis, if accepted, will greatly impact translational medicine especially in the treatment of cancer, since apoptosis is generally irreversible in the late stages, and chemotherapy is performed to maximize tumor death and minimize off-target effects...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29149522/melatonin-improves-the-meiotic-maturation-of-porcine-oocytes-by-reducing-endoplasmic-reticulum-stress-during-in-vitro-maturation
#2
Hyo-Jin Park, Jae-Young Park, Jin-Woo Kim, Seul-Gi Yang, Jae-Min Jung, Min-Ji Kim, Man-Jong Kang, Young Ho Cho, Gabbine Wee, Hee-Young Yang, Bong-Seok Song, Sun-Uk Kim, Deog-Bon Koo
Under endoplasmic reticulum (ER)-stress conditions, the unfolded protein response (UPR) generates a defense mechanism in mammalian cells. The regulation of UPR signaling is important in oocyte maturation, embryo development, and female reproduction of pigs. Recent studies have shown that melatonin plays an important role as an anti-oxidant to improve pig oocyte maturation. However, there is no report on the role of melatonin in the regulation of UPR signaling and ER-stress during in vitro maturation (IVM) of porcine oocytes...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29148236/emerging-roles-of-er-stress-in-the-aetiology-and-pathogenesis-of-alzheimer-s-disease
#3
REVIEW
Yannis Gerakis, Claudio Hetz
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by synaptic dysfunction and accumulation of abnormal aggregates formed by amyloid-β peptides or phophorylated Tau proteins. Accumulating evidence suggests that alterations in the buffering capacity of the proteostasis network is a salient feature of AD. The endoplasmic reticulum (ER) is the main compartment involved in protein folding and secretion and is drastically affected in AD neurons. ER stress triggers the activation of the Unfolded Protein Response (UPR), a signal transduction pathway that enforces adaptive programs to recover homeostasis or trigger apoptosis of irreversibly damaged cells...
November 17, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29145850/targeting-protein-quality-control-pathways-in-breast-cancer
#4
REVIEW
Sara Sannino, Jeffrey L Brodsky
The efficient production, folding, and secretion of proteins is critical for cancer cell survival. However, cancer cells thrive under stress conditions that damage proteins, so many cancer cells overexpress molecular chaperones that facilitate protein folding and target misfolded proteins for degradation via the ubiquitin-proteasome or autophagy pathway. Stress response pathway induction is also important for cancer cell survival. Indeed, validated targets for anti-cancer treatments include molecular chaperones, components of the unfolded protein response, the ubiquitin-proteasome system, and autophagy...
November 16, 2017: BMC Biology
https://www.readbyqxmd.com/read/29145399/point-mutation-in-d8c-domain-of-tamm-horsfall-protein-uromodulin-in-transgenic-mice-causes-progressive-renal-damage-and-hyperuricemia
#5
Lijie Ma, Yan Liu, Nichole K Landry, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Hereditary mutations in Tamm-Horsfall protein (THP/uromodulin) gene cause autosomal dominant kidney diseases characterized by juvenile-onset hyperuricemia, gout and progressive kidney failure, although the disease pathogenesis remains unclear. Here we show that targeted expression in transgenic mice of a mutation within the domain of 8 cysteines of THP in kidneys' thick ascending limb (TAL) caused unfolded protein response in younger (1-month old) mice and apoptosis in older (12-month old) mice. While the young mice had urine concentration defects and polyuria, such defects progressively reversed in the older mice to marked oliguria, highly concentrated urine, fibrotic kidneys and reduced creatinine clearance...
2017: PloS One
https://www.readbyqxmd.com/read/29142472/prostaglandin-e1-protects-hepatocytes-against-endoplasmic-reticulum-stress-induced-apoptosis-via-protein-kinase-a-dependent-induction-of-glucose-regulated-protein-78-expression
#6
Fang-Wan Yang, Yu Fu, Ying Li, Yi-Huai He, Mao-Yuan Mu, Qi-Chuan Liu, Jun Long, Shi-De Lin
AIM: To investigate the protective effect of prostaglandin E1 (PGE1) against endoplasmic reticulum (ER) stress-induced hepatocyte apoptosis, and to explore its underlying mechanisms. METHODS: Thapsigargin (TG) was used to induce ER stress in the human hepatic cell line L02 and hepatocarcinoma-derived cell line HepG2. To evaluate the effects of PGE1 on TG-induced apoptosis, PGE1 was used an hour prior to TG treatment. Activation of unfolded protein response signaling pathways were detected by western blotting and quantitative real-time RT-PCR...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29138281/a-conserved-cytoskeletal-signaling-cascade-mediates-neurotoxicity-of-ftdp-17-tau-mutations-in-vivo
#7
Farah H Bardai, Liqun Wang, Yamini Mutreja, Mythili Yenjerla, T Chris Gamblin, Mel B Feany
The microtubule binding protein tau is strongly implicated in multiple neurodegenerative disorders, including frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), which is caused by mutations in tau. In vitro, FTDP-17 mutant versions of tau can reduce microtubule binding and increase aggregation of tau, but the mechanism by which these mutations promote disease in vivo is not clear. Here we take a combined biochemical and in vivo modeling approach to define functional properties of tau driving neurotoxicity in vivo We express wild type human tau and five FTDP-17 mutant forms of tau in Drosophila using a site-directed insertion strategy to ensure equivalent levels of expression...
November 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29137221/anti-pancreatic-cancer-activity-of-onc212-involves-the-unfolded-protein-response-upr-and-is-reduced-by-igf1-r-and-grp78-bip
#8
Avital Lev, Amriti R Lulla, Jessica Wagner, Marie D Ralff, Joshua B Kiehl, Yan Zhou, Cyril H Benes, Varun V Prabhu, Wolfgang Oster, Igor Astsaturov, David T Dicker, Wafik S El-Deiry
Pancreatic cancer is chemo-resistant and metastasizes early with an overall five-year survival of ∼8.2%. First-in-class imipridone ONC201 is a small molecule in clinical trials with anti-cancer activity. ONC212, a fluorinated-ONC201 analogue, shows preclinical efficacy in melanoma and hepatocellular-cancer models. We investigated efficacy of ONC201 and ONC212 against pancreatic cancer cell lines (N=16 including 9 PDX-cell lines). We demonstrate ONC212 efficacy in 4 in-vivo models including ONC201-resistant tumors...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136510/genomic-subtypes-of-non-invasive-bladder-cancer-with-distinct-metabolic-profile-and-female-gender-bias-in-kdm6a-mutation-frequency
#9
Carolyn D Hurst, Olivia Alder, Fiona M Platt, Alastair Droop, Lucy F Stead, Julie E Burns, George J Burghel, Sunjay Jain, Leszek J Klimczak, Helen Lindsay, Jo-An Roulson, Claire F Taylor, Helene Thygesen, Angus J Cameron, Anne J Ridley, Helen R Mott, Dmitry A Gordenin, Margaret A Knowles
Bladder cancer incurs a higher lifetime treatment cost than other cancers due to frequent recurrence of non-invasive disease. Improved prognostic biomarkers and localized therapy are needed for this large patient group. We defined two major genomic subtypes of primary stage Ta tumors. One of these was characterized by loss of 9q including TSC1, increased KI67 labeling index, upregulated glycolysis, DNA repair, mTORC1 signaling, features of the unfolded protein response, and altered cholesterol homeostasis. Comparison with muscle-invasive bladder cancer mutation profiles revealed lower overall mutation rates and more frequent mutations in RHOB and chromatin modifier genes...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29129774/crosstalk-between-endoplasmic-reticulum-stress-and-brain-inflammation-in-alzheimer-s-disease
#10
REVIEW
Luis E Santos, Sergio T Ferreira
While most often noted for its cognitive symptoms, Alzheimer's disease (AD) is, at its core, a disease of protein misfolding/aggregation, with an intriguing inflammatory component. Defective clearance and/or abnormal production of the amyloid-β peptide (Aβ), and its ensuing accumulation and aggregation, underlie two hallmark features of AD: brain accumulation of insoluble protein deposits known as amyloid or senile plaques, and buildup of soluble Aβ oligomers (AβOs), diffusible toxins linked to synapse dysfunction and memory impairment...
November 9, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29124827/recovery-from-temporary-er-stress-in-plants-relies-on-tissue-specific-and-largely-independent-roles-of-bzip28-and-bzip60-as-well-as-an-antagonizing-function-of-bax-inhibitor1-onto-the-pro-adaptive-signaling-mediated-by-bzip28
#11
Cristina Ruberti, YaShiuan Lai, Federica Brandizzi
The unfolded protein response (UPR) is an ancient signaling pathway that commits to life-or-death outcomes in response to proteotoxic stress in the endoplasmic reticulum (ER). In plants, the membrane-tethered transcription factor bZIP28 and the ribonuclease-kinase IRE1 along with its splicing target, bZIP60, govern the two cytoprotective UPR signaling pathways known to date. The conserved ER membrane-associated BAX inhibitor1 (BI1) modulates ER stress-induced programmed cell death through yet-unknown mechanisms...
November 10, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29123984/transmembrane-thioredoxin-related-protein-tmx1-is-reversibly-oxidized-in-response-to-protein-accumulation-in-the-endoplasmic-reticulum
#12
Yoshiyuki Matsuo, Kiichi Hirota
Numerous secretory and membrane proteins undergo post-translational modifications in the endoplasmic reticulum (ER), and the formation of disulfide bonds is a modification that is critical for proper protein folding. The mammalian ER contains a large family of oxidoreductases that are considered to catalyze thiol/disulfide exchange and ensure the maintenance of a redox environment within the ER. Disruption of ER homeostasis causes an accumulation of misfolded and unfolded proteins, a condition termed ER stress...
November 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/29123254/implications-of-aging-and-the-endoplasmic-reticulum-unfolded-protein-response-on-the-molecular-modality-of-breast-cancer
#13
REVIEW
Rinki Minakshi, Safikur Rahman, Arif Tasleem Jan, Ayyagari Archana, Jihoe Kim
The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca(2+). The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death...
November 10, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29120414/genetic-variation-in-glia-neuron-signalling-modulates-ageing-rate
#14
Jiang-An Yin, Ge Gao, Xi-Juan Liu, Zi-Qian Hao, Kai Li, Xin-Lei Kang, Hong Li, Yuan-Hong Shan, Wen-Li Hu, Hai-Peng Li, Shi-Qing Cai
The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps...
November 8, 2017: Nature
https://www.readbyqxmd.com/read/29118753/intestinal-epithelial-cell-endoplasmic-reticulum-stress-and-inflammatory-bowel-disease-pathogenesis-an-update-review
#15
REVIEW
Xiaoshi Ma, Zhaolai Dai, Kaiji Sun, Yunchang Zhang, Jingqing Chen, Ying Yang, Patrick Tso, Guoyao Wu, Zhenlong Wu
The intestinal epithelial cells serve essential roles in maintaining intestinal homeostasis, which relies on appropriate endoplasmic reticulum (ER) function for proper protein folding, modification, and secretion. Exogenous or endogenous risk factors with an ability to disturb the ER function can impair the intestinal barrier function and activate inflammatory responses in the host. The last decade has witnessed considerable progress in the understanding of the functional role of ER stress and unfolded protein response (UPR) in the gut homeostasis and its significant contribution to the pathogenesis of inflammatory bowel disease (IBD)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#16
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small molecule modulators of Sigma1 alter endoplasmic reticulum (ER) associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type 1 integral membrane glycoprotein that is co-translationally inserted into the ER and is processed and transported through the secretory pathway...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117551/distinct-roles-of-sensory-neurons-in-mediating-pathogen-avoidance-and-neuropeptide-dependent-immune-regulation
#17
Xiou Cao, Rie Kajino-Sakamoto, Argenia Doss, Alejandro Aballay
Increasing evidence implies an extensive and universal interaction between the immune system and the nervous system. Previous studies showed that OCTR-1, a neuronal G-protein-coupled receptor (GPCR) analogous to human norepinephrine receptors, functions in sensory neurons to control the gene expression of both microbial killing pathways and the unfolded protein response (UPR) in Caenorhabditis elegans. Here, we found that OCTR-1-expressing neurons, ASH, are involved in controlling innate immune pathways. In contrast, another group of OCTR-1-expressing neurons, ASI, was shown to promote pathogen avoidance behavior...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29114219/entanglement-of-upr-er-in-aging-driven-neurodegenerative-diseases
#18
REVIEW
Safikur Rahman, Arif Tasleem Jan, Archana Ayyagari, Jiwoo Kim, Jihoe Kim, Rinki Minakshi
The endoplasmic reticulum (ER) is an indispensable cellular organelle that remains highly active in neuronal cells. The ER bears the load of maintaining protein homeostasis in the cellular network by managing the folding of incoming nascent peptides; however, the stress imposed by physiological/environmental factors can cause ER dysfunctions that lead to the activation of ER unfolded protein response (UPR(ER)). Aging leads to deterioration of several cellular pathways and therefore weakening of the UPR(ER)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29113324/unfolded-protein-response-signaling-impacts-macrophage-polarity-to-modulate-breast-cancer-cell-clearance-and-melanoma-immune-checkpoint-therapy-responsiveness
#19
David R Soto-Pantoja, Adam S Wilson, Kenysha Yj Clear, Brian Westwood, Pierre L Triozzi, Katherine L Cook
The unfolded protein response (UPR) is a stress pathway controlled by GRP78 to mediate IRE1, PERK, and ATF6 signaling. We show that targeting GRP78, IRE1, and PERK differentially regulates macrophage polarization. Specifically, PERK targeting enhanced macrophage proliferation and macrophage-mediated killing but not GRP78 or IRE1. Targeting UPR in cancer cells also differentially affected macrophage cytolytic capacity. Tumoral IRE1 or GRP78 inhibition enhanced macrophage-mediated cancer cell clearance. Conditioned media from GRP78-silenced cancer cells caused reciprocal regulation of CD80 and CD206, suggesting control of plasticity by secreted factors...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29113061/effects-of-marine-oils-digested-with-human-fluids-on-cellular-viability-and-stress-protein-expression-in-human-intestinal-caco-2-cells
#20
Cecilia Tullberg, Gerd Vegarud, Ingrid Undeland, Nathalie Scheers
In vitro digestion of marine oils has been reported to promote lipid oxidation, including the formation of reactive aldehydes (e.g., malondialdehyde (MDA) and 4-hydroxy-2-hexenal (HHE)). We aimed to investigate if human in vitro digestion of supplemental levels of oils from algae, cod liver, and krill, in addition to pure MDA and HHE, affect intestinal Caco-2 cell survival and oxidative stress. Cell viability was not significantly affected by the digests of marine oils or by pure MDA and HHE (0-90 μM). Cellular levels of HSP-70, a chaperone involved in the prevention of stress-induced protein unfolding was significantly decreased (14%, 28%, and 14% of control for algae, cod and krill oil, respectively; p ≤ 0...
November 4, 2017: Nutrients
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