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https://www.readbyqxmd.com/read/27922637/a-human-carboxypeptidase-e-nf-%C3%AE-1-gene-mutation-in-an-alzheimer-s-disease-patient-leads-to-dementia-and-depression-in-mice
#1
Y Cheng, N X Cawley, T Yanik, S R K Murthy, C Liu, F Kasikci, D Abebe, Y P Loh
Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27920253/bmp-induces-osteoblast-differentiation-through-both-smad4-and-mtorc1-signaling
#2
Courtney M Karner, Seung-Yon Lee, Fanxin Long
The bone morphogenetic protein (Bmp) family of secreted molecules has been extensively studied in the context of osteoblast differentiation. However, the intracellular signaling cascades mediating the osteoblastogenic function of Bmp have not been fully elucidated. By profiling mRNA expression in the bone marrow mesenchymal progenitor cell line ST2 cells, we discover that BMP2 induces not only genes commonly associated with ossification and mineralization, but also genes important for general protein synthesis...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27920251/a-homeostatic-shift-facilitates-endoplasmic-reticulum-proteostasis-through-transcriptional-integration-of-proteostatic-stress-response-pathways
#3
Liam Baird, Tadayuki Tsujita, Eri Kobayashi, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Masayuki Yamamoto
Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Whilst the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system (UPS), which functions to degrade damaged, unfolded or short half-life proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27919320/calcium-mediated-actin-reset-caar-mediates-acute-cell-adaptations
#4
Pauline Wales, Christian E Schuberth, Roland Aufschnaiter, Johannes Fels, Ireth García-Aguilar, Annette Janning, Christopher P Dlugos, Marco Schäfer-Herte, Christoph Klingner, Mike Wälte, Julian Kuhlmann, Ekaterina Menis, Laura Hockaday Kang, Kerstin C Maier, Wenya Hou, Antonella Russo, Henry N Higgs, Hermann Pavenstädt, Thomas Vogl, Johannes Roth, Britta Qualmann, Michael M Kessels, Dietmar E Martin, Bela Mulder, Roland Wedlich-Söldner
Actin has well established functions in cellular morphogenesis. However, it is not well understood how the various actin assemblies in a cell are kept in a dynamic equilibrium, in particular when cells have to respond to acute signals. Here, we characterize a rapid and transient actin reset in response to increased intracellular calcium levels. Within seconds of calcium influx, the formin INF2 stimulates filament polymerization at the endoplasmic reticulum (ER), while cortical actin is disassembled. The reaction is then reversed within a few minutes...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27918551/hepatocarcinogenesis-in-transgenic-mice-carrying-hepatitis-b-virus-pre-s-s-gene-with-the-sw172-mutation
#5
M-W Lai, K-H Liang, W-R Lin, Y-H Huang, S-F Huang, T-C Chen, C-T Yeh
Hepatitis B virus (HBV) carrying the rtA181T/sW172* mutation conferred cross-resistance to adefovir and lamivudine. Cell-based and clinical studies indicated that HBV carrying this mutation had an increased oncogenic potential. Herein, we created transgenic mouse models to study the oncogenicity of the HBV pre-S/S gene containing this mutation. Transgenic mice were generated by transfer of the HBV pre-S/S gene together with its own promoter into C57B6 mice. Four lines of mice were created. Two of them carried wild-type gene and produced high and low levels of HBV surface antigen (HBsAg) (TgWT-H and L)...
December 5, 2016: Oncogenesis
https://www.readbyqxmd.com/read/27917829/the-er-stress-sensor-perk-luminal-domain-functions-as-a-molecular-chaperone-to-interact-with-misfolded-proteins
#6
Peng Wang, Jingzhi Li, Bingdong Sha
PERK is one of the major sensor proteins which can detect the protein-folding imbalance generated by endoplasmic reticulum (ER) stress. It remains unclear how the sensor protein PERK is activated by ER stress. It has been demonstrated that the PERK luminal domain can recognize and selectively interact with misfolded proteins but not native proteins. Moreover, the PERK luminal domain may function as a molecular chaperone to directly bind to and suppress the aggregation of a number of misfolded model proteins...
December 1, 2016: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/27916883/enhanced-autophagy-in-polycystic-kidneys-of-aqp11-null-mice
#7
Yasuko Tanaka, Mayumi Watari, Tatsuya Saito, Yoshiyuki Morishita, Kenichi Ishibashi
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27916083/-effects-of-chronic-intermittent-hypoxia-on-hepatic-function-and-protective-mechanism-of-adiponectin-in-rats
#8
R Xue, J Cao, X L Zhang, W X Ding, W J Wang, H P Huang
Objective: To explore the effect of chronic intermittent hypoxia (CIH) on rats hepatic function, and the protective mechanism of adiponectin (Ad). Methods: Sixty healthy male wistar rats were randomly divided into 4 groups: normal control (NC), NC+ Ad, CIH, and CIH+ Ad groups with 15 rats in each. The rats in CIH and CIH+ Ad groups were exposed to an intermittent hypoxic chamber 8 hours per day for 4 months. Meanwhile, the rats in both the NC and NC + Ad groups were housed with normal pressure air. The rats in the NC+ Ad and CIH+ Ad groups were additionally treated with an intravenous injection of Ad (10 μg), twice a week for 4 months...
November 29, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27915415/exendin-4-protects-huvecs-from-tunicamycin-induced-apoptosis-via-inhibiting-the-ire1a-jnk-caspase-3-pathway
#9
Li Wu, XiaoYing Liu, LinXi Wang, YanPing Wang, LiJing Wang, BinBin Guan, Zhou Chen, LiBin Liu
PURPOSE: The abnormal increase of apoptosis of endothelial cells induced by endoplasmic reticulum stress is a significant factor for vascular disease, especially for atherosclerosis. Protecting endothelial cells from endoplasmic reticulum stress is a crucial strategies to combate these diseases. The goal of this study was to explore the effect of Exendin-4, a glucagon-like peptide-1 receptor agonist, on tunicamycin-induced apoptosis in human umbilical vein endothelial cells. METHODS: All studies were performed in primary human umbilical vein endothelial cells treated with tunicamycin with or without Exendin-4 pretreatment...
December 3, 2016: Endocrine
https://www.readbyqxmd.com/read/27914648/atomization-method-for-verifying-size-effects-of-inhalable-particles-on-lung-damage-of-mice
#10
Chen Tao, Yue Tang, Lan Zhang, Yonggang Tian, Yingmei Zhang
To explore the size effects of inhalable particles on lung damage, aqueous aerosol containing cadmium was studied as a model to design a new type of two-stage atomization device that was composed of two adjustable parts with electronic ultrasonic atomization and pneumatic atomization. The working parameters and effectiveness of this device were tested with H2O atomization and CdCl2 inhalation, respectively. By gravimetrically detecting the mass concentrations of PM2.5 and PM10 and analysing the particle size with a laser sensor, we confirmed the particle size distribution of the aqueous aerosol produced by the new device under different working conditions...
December 1, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27914514/protective-effects-of-fish-oil-and-pioglitazone-on-pancreatic-tissue-in-obese-kk-mice-with-type-2-diabetes
#11
Yuzuru Iizuka, Hyounju Kim, Takuya Izawa, Koji Sakurai, Satoshi Hirako, Masahiro Wada, Akiyo Matsumoto
n-3 Polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have protective effects against the pancreatic β-cell dysfunction through several mechanisms. Thiazolidines are insulin sensitizers and are used in treating patients with type 2 diabetes. Our previous study demonstrated that a combination of fish oil, which is rich with EPA and DHA, and pioglitazone exerts beneficial effects on obesity and diabetes through their actions on the liver and adipose tissue. However, it remains largely unknown whether such combination therapy affects the pancreas...
December 2016: Prostaglandins, Leukotrienes, and Essential Fatty Acids
https://www.readbyqxmd.com/read/27913816/genetic-ablation-or-pharmacologic-inhibition-of-autophagy-mitigated-nsaid-associated-gastric-damages
#12
Chan Young Ock, Jong-Min Park, Young-Min Han, Migyeong Jeong, Mi-Young Kim, Ho Jae Lee, Ki Baik Hahm
: Non-steroidal anti-inflammatory drug (NSAID)-associated endoplasmic reticulum (ER) stress (a cyclooxygenase-2-independent mechanism) and consequent autophagic cell death are responsible for NSAID-associated gastric damage. Therefore, alleviating cytotoxicity executed via ER stress and autophagy can be a strategy to prevent NSAID-associated gastric damage. Here, we explored whether genetic or pharmacologic inhibition of autophagy can mitigate NSAID-associated gastric damage in in vitro and in vivo models...
December 2, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27913641/translation-repression-by-maternal-rna-binding-protein-zar1-is-essential-for-early-oogenesis-in-zebrafish
#13
Liyun Miao, Yue Yuan, Feng Cheng, Junshun Fang, Fang Zhou, Weirui Ma, Yan Jiang, Xiahe Huang, Yingchun Wang, Lingjuan Shan, Dahua Chen, Jian Zhang
Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27913278/molecular-basis-for-the-dual-subcellular-distribution-of-microsomal-glutathione-transferase-1
#14
Miyuki Shimoji, Ricardo A Figueroa, Etienne Neve, Danuta Maksel, Gabriela Imreh, Ralf Morgenstern, Einar Hallberg
Microsomal glutathione transferase 1 (MGST1) is a membrane bound enzyme involved in the detoxification of reactive electrophiles and protection of membranes from oxidative stress. The enzyme displays an unusual and broad subcellular distribution with especially high levels in the endoplasmic reticulum (ER) and outer mitochondrial membrane (OMM). Here we examined the molecular basis for this dual distribution. We hypothesized that the amphipathic properties of the first transmembrane segment (TMS), that contains a positively charged lysine (K25), is a central feature guiding dual targeting...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911723/ribonucleoprotein-bodies-are-phased-in
#15
REVIEW
Aristeidis P Sfakianos, Alan J Whitmarsh, Mark P Ashe
Intracellular compartments are necessary for the regulation of many biochemical processes that ensure cell survival, growth and proliferation. Compartmentalisation is commonly achieved in organelles with defined lipid membranes, such as mitochondria, endoplasmic reticulum or the Golgi apparatus. While these organelles are responsible for many localised biochemical processes, recent evidence points to another class of compartments that lack membrane boundaries. The structure and content of these bodies depend on their function and subcellular localisation, but they mainly incorporate proteins and RNA...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911441/sirt1-protects-the-heart-from-er-stress-induced-cell-death-through-eif2%C3%AE-deacetylation
#16
Alexandre Prola, Julie Pires Da Silva, Arnaud Guilbert, Lola Lecru, Jérôme Piquereau, Maxance Ribeiro, Philippe Mateo, Mélanie Gressette, Dominique Fortin, Céline Boursier, Cindy Gallerne, Anaïs Caillard, Jane-Lise Samuel, Hélène François, David A Sinclair, Pierre Eid, Renée Ventura-Clapier, Anne Garnier, Christophe Lemaire
Over the past decade, endoplasmic reticulum (ER) stress has emerged as an important mechanism involved in the pathogenesis of cardiovascular diseases including heart failure. Cardiac therapy based on ER stress modulation is viewed as a promising avenue toward effective therapies for the diseased heart. Here, we tested whether sirtuin-1 (SIRT1), a NAD(+)-dependent deacetylase, participates in modulating ER stress response in the heart. Using cardiomyocytes and adult-inducible SIRT1 knockout mice, we demonstrate that SIRT1 inhibition or deficiency increases ER stress-induced cardiac injury, whereas activation of SIRT1 by the SIRT1-activating compound STAC-3 is protective...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27910195/mulberrofuran-g-protects-ischemic-injury-induced-cell-death-via-inhibition-of-nox4-mediated-ros-generation-and-er-stress
#17
Sungeun Hong, Jaeyoung Kwon, Dong-Woo Kim, Hak Ju Lee, Dongho Lee, Woongchon Mar
The aim of this study was to investigate the neuroprotective effect of mulberrofuran G (MG) in in vitro and in vivo models of cerebral ischemia. MG was isolated from the root bark of Morus bombycis. MG inhibited nicotinamide adenine dinucleotide phosphate oxidase (NOX) enzyme activity and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced NOX4 protein expression in SH-SY5Y cells. MG inhibited the expression of activated caspase-3 and caspase-9 and cleaved poly adenine dinucleotide phosphate-ribose polymerase in OGD/R-induced SH-SY5Y cells...
December 2, 2016: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/27909574/characterization-of-5-2-18-f-fluoroethoxy-l-tryptophan-for-pet-imaging-of-the-pancreas
#18
Ahmed Abbas, Christine Beamish, Rebecca McGirr, John Demarco, Neil Cockburn, Dawid Krokowski, Ting-Yim Lee, Michael Kovacs, Maria Hatzoglou, Savita Dhanvantari
Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2- (18)F-fluoroethoxy)-L-tryptophan ( (18)F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes. Procedures: Uptake of (18)F-L-FEHTP was determined in wild-type C57BL/6 mice by ex vivo biodistribution...
2016: F1000Research
https://www.readbyqxmd.com/read/27909053/endoplasmic-reticulum-stress-and-ca2-depletion-differentially-modulate-the-sterol-regulatory-protein-pcsk9-to-control-lipid-metabolism
#19
Paul Lebeau, Ali Al-Hashimi, Sudesh Sood, Sarka Lhotak, Pei Yu, Gabriel Gyulay, Guillaume Pare, S R Wayne Chen, Bernardo Trigatti, Annik Prat, Nabil Seidah, Richard C Austin
Accumulating evidence implicates endoplasmic reticulum (ER) stress as a mediator of impaired lipid metabolism, thereby contributing to fatty liver disease and atherosclerosis. Previous studies demonstrated that ER stress can activate the sterol regulatory element-binding protein-2 (SREBP2), an ER localized transcription factor that directly upregulates sterol-regulatory genes, including PCSK9. Given that PCSK9 contributes to atherosclerosis by targeting low-density lipoprotein (LDL) receptor (LDLR) degradation, our present study investigates a novel mechanism by which ER stress plays a role in lipid metabolism by examining its ability to modulate PCSK9 expression...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27907038/equol-attenuates-atherosclerosis-in-apolipoprotein-e-deficient-mice-by-inhibiting-endoplasmic-reticulum-stress-via-activation-of-nrf2-in-endothelial-cells
#20
Ting Zhang, Qin Hu, Linying Shi, Li Qin, Qianyong Zhang, Mantian Mi
The development of atherosclerosis is closely related to excessive endoplasmic reticulum stress (ERs). Equol reportedly protects against cardiovascular disease; however, the underlying mechanism for this protection remains unknown. Herein, the mechanisms contributing to the atheroprotective effect of equol were addressed using apolipoprotein E knockout (apoE-/-) mice fed a high-fat diet (HFD) with or without equol. Equol intervention reduced atherosclerotic lesions in the aorta in HFD-fed apoE-/- mice. Plasma lipid analysis showed that equol intervention reduced triglycerides, total cholesterol and LDL-cholesterol and increased HDL-cholesterol...
2016: PloS One
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