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https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#1
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
August 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28821541/targeting-mir-423-5p-reverses-exercise-training-induced-hcn4-channel-remodeling-and-sinus-bradycardia
#2
Alicia D'Souza, Charles M Pearman, Yanwen Wang, Shu Nakao, Sunil Jit R Logantha, Charlotte Cox, Hayley J Bennett, Yu Zhang, Anne Berit Johnsen, Nora Linscheid, Pi C Poulsen, Jonathan Elliott, Jessica Coulson, Jamie S McPhee, Abigail C Robertson, Paula A da Costa Martins, Ashraf Kitmitto, Ulrik Wisloff, Elizabeth J Cartwright, Oliver Monfredi, Alicia Lundby, Halina Dobrzynski, Delvac Oceandy, Gwilym M Morris, Mark R Boyett
Rationale: Downregulation of the pacemaking ion channel, HCN4, and the corresponding ionic current, If, underlies exercise training-induced sinus bradycardia in rodents. If this occurs in humans, it could explain the increased incidence of bradyarrhythmias in veteran athletes and it will be important to understand the underlying processes. Objective: To test the role of HCN4 in the training-induced bradycardia in human athletes and investigate the role of micro-RNAs (miRs) in the repression of HCN4. Methods and Results: As in rodents, the intrinsic heart rate was significantly lower in human athletes than non-athletes and in all subjects the rate-lowering effect of the HCN selective blocker, ivabradine, was significantly correlated with the intrinsic heart rate, consistent with HCN repression in athletes...
August 17, 2017: Circulation Research
https://www.readbyqxmd.com/read/28821490/serca-directs-cell-migration-and-branching-across-species-and-germ-layers
#3
Danielle V Bower, Nick Lansdale, Sonia Navarro, Thai V Truong, Dan J Bower, Neil C Featherstone, Marilyn G Connell, Denise Al-Alam, Mark R Frey, Le A Trinh, G Esteban Fernandez, David Warburton, Scott E Fraser, Daimark Bennett, Edwin C Jesudason
Branching morphogenesis underlies organogenesis in vertebrates and invertebrates, yet is incompletely understood. Here, we show that the sarco-endoplasmic reticulum Ca(2+) reuptake pump (SERCA) directs budding across germ layers and species. Clonal knockdown demonstrated a cell-autonomous role for SERCA in Drosophila air sac budding. Live imaging of Drosophila tracheogenesis revealed elevated Ca(2+) levels in migratory tip cells as they form branches. SERCA blockade abolished this Ca(2+) differential, aborting both cell migration and new branching...
August 17, 2017: Biology Open
https://www.readbyqxmd.com/read/28821209/cued-memory-reactivation-during-sws-abolishes-the-beneficial-effect-of-sleep-on-abstraction
#4
Nora Hennies, Matthew A Lambon Ralph, Simon J Durrant, James N Cousins, Penelope A Lewis
Study Objectives: Extracting regularities from stimuli in our environment and generalizing these to new situations are fundamental processes in human cognition. Sleep has been shown to enhance these processes, possibly by facilitating reactivation-triggered memory reorganization. Here, we assessed whether cued reactivation during slow wave sleep (SWS) promotes the beneficial effect of sleep on abstraction of statistical regularities. Methods: We used an auditory statistical learning task, in which the benefit of sleep has been firmly established...
August 1, 2017: Sleep
https://www.readbyqxmd.com/read/28820076/a-novel-danshensu-tetramethylpyrazine-conjugate-dt-018-provides-cardioprotection-by-preserving-mitochondrial-function-through-the-mef2d-pgc-1%C3%AE-pathway
#5
Xiaojing Zhang, Jingxiong Luo, Yali Huang, Huixing Deng, Huihui Hu, Pei Yu, Yewei Sun, Luchen Shan, Yuqiang Wang
In this work, we explored the protective effect of DT-018, a danshensu and tetramethylpyrazine conjugate, on mitochondrial injury induced by tert-butylhydroperoxide (t-BHP) and its possible mechanisms of action. DT-018 effectively quenched intracellular and mitochondrial reactive oxygen species (ROS), preserved the mitochondrial function, restored the intracellular level of ATP and augmented mitochondrial membrane potential (ΔΨm) while suppressed mitochondrial swelling in isolated myocardial mitochondria...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28819881/resveratrol-induces-apoptosis-and-inhibits-adipogenesis-by-stimulating-the-sirt1-ampk%C3%AE-foxo1-signalling-pathway-in-bovine-intramuscular-adipocytes
#6
Xiaomu Liu, Hongbo Zhao, Qing Jin, Wei You, Haijian Cheng, Yifan Liu, Enliang Song, Guifen Liu, Xiuwen Tan, Xianglun Zhang, Fachun Wan
Sirtuin type 1 (SIRTl) and AMP-activated protein kinase (AMPK) play important roles in regulating energy metabolism, cell proliferation and differentiation, ageing, apoptosis, and metabolism. The effect of 100, 200, and 400 μm Resveratrol (RES), an activator of SIRT1, on apoptosis of bovine intramuscular adipocytes was investigated by nuclear staining, flow cytometry, quantitative real-time polymerase chain reaction, and western blotting. Results show that RES inhibited adipogenesis, decreased cell viability, and increased apoptotic rates in a dose-dependent way...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28819643/membrane-localization-of-acetylated-cnk1-mediates-a-positive-feedback-on-raf-erk-signaling
#7
Adrian Fischer, Wignand W D Mühlhäuser, Bettina Warscheid, Gerald Radziwill
Spatiotemporal control is a common mechanism that modulates activity and function of signal transducers in the signaling network. We identified acetylation of CNK1 (connector enhancer of kinase suppressor of Ras-1) as a late step in the activation of CNK1 signaling, accompanied with prolonged stimulation of extracellular signal-regulated kinase (ERK). We identified the acetyltransferase CREB (cyclic adenosine 3',5'-monophosphate response element-binding protein)-binding protein and the deacetylase SIRT2 (sirtuin type 2) as novel binding partners of CNK1, modulating the acetylation state of CNK1...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28819560/a-novel-peptide-blocking-cancer-cell-invasion-by-structure-based-drug-design
#8
Yuki Yamada, Seiji Kanayama, Fuminori Ito, Noriyuki Kurita, Hiroshi Kobayashi
The receptor for the urokinase-type plasminogen activator (uPA), uPAR, facilitates tumor cell invasion and metastasis by focusing on several ligands, including uPA, integrins and vitronectin. With computational prediction algorithms and structure-based drug design, we identified peptides containing the Gly-Lys-Gly-Glu-Gly-Glu-Gly-Lys-Gly sequence (peptide H1), which strongly interacts with uPAR. The aim of the present study was to investigate the effect of allosteric inhibition at the uPAR interface using a novel synthetic peptide and its function on ovarian cancer cell invasion...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28819393/phosphoglycerate-mutase-1-predicts-the-poor-prognosis-of-oral-squamous-cell-carcinoma-and-is-associated-with-cell-migration
#9
Dadong Zhang, Heming Wu, Xiaomin Zhang, Xu Ding, Min Huang, Meiyu Geng, Hongwei Li, Zuoquan Xie
Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential. However, no good biomarker has been identified to refine which subtype is of high metastatic potential to make decisions regarding the elective and therapeutic management of lymphatic metastases. In this study, we investigated the role of the metabolic enzyme phosphoglycerate mutase 1 (PGAM1) in OSCC. PGAM1 expression was examined in tissue samples of 122 OSCC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28818753/benzoylsalicylic-acid-derivatives-as-defense-activators-in-tobacco-and-arabidopsis
#10
Samuel Kamatham, Reddanna Pallu, Anil Kumar Pasupulati, Surya Satyanarayana Singh, Padmaja Gudipalli
Systemic acquired resistance (SAR) is a long lasting inducible whole plant immunity often induced by either pathogens or chemical elicitors. Salicylic acid (SA) is a known SAR signal against a broad spectrum of pathogens in plants. In a recent study, we have reported that benzoylsalicylic acid (BzSA) is a SAR inducer in tobacco and Arabidopsis plants. Here, we have synthesized BzSA derivatives using SA and benzoyl chlorides of various moieties as substrates. The chemical structures of BzSA derivatives were elucidated using Infrared spectroscopy (IR), Nuclear magnetic spectroscopy (NMR) and High-resolution mass spectrometer (HRMS) analysis...
August 14, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28817623/metformin-attenuates-myocardial-ischemia-reperfusion-injury-via-up-regulation-of-antioxidant-enzymes
#11
Xiaoling Wang, Lei Yang, Licheng Kang, Jing Li, Liang Yang, Jincai Zhang, Jie Liu, Mengmeng Zhu, Qiong Zhang, Yanna Shen, Zhi Qi
The objective was to examine the protective effect of metformin (Met) on myocardial ischemia-reperfusion (IR) injury and whether the mechanism was related to the AMPK/ antioxidant enzymes signaling pathway. Rat Langendorff test and H2O2-treated rat cardiomyocytes (H9c2) were used in this study. Met treatment significantly improved left ventricular (LV) function, reduced infarct size and CK-MB release in comparison with IR group. Decreased TUNEL staining positive cells were also observed in IR+Met group ex vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28817268/natural-organic-matter-concentration-impacts-the-interaction-of-functionalized-diamond-nanoparticles-with-model-and-actual-bacterial-membranes
#12
Arielle C Mensch, Rodrigo Tapia Hernandez, Joshua E Kuether, Marco D Torelli, Z Vivian Feng, Robert J Hamers, Joel A Pedersen
Changes to nanoparticle surface charge, colloidal stability, and hydrodynamic properties induced by interaction with natural organic matter (NOM) warrant consideration in assessing the potential for these materials to adversely impact organisms in the environment. Here we show that acquisition of a coating, or "corona", of NOM alters the hydrodynamic and electrokinetic properties of diamond nanoparticles (DNPs) functionalized with the polycation poly(allylamine HCl) in a manner that depends on the NOM-to-DNP concentration ratio...
August 17, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28816632/the-liver-circadian-clock-modulates-biochemical-and-physiological-responses-to-metformin
#13
Emma Henriksson, Anne-Laure Huber, Erin K Soto, Anna Kriebs, Megan E Vaughan, Drew Duglan, Alanna B Chan, Stephanie J Papp, Madelena Nguyen, Megan E Afetian, Katja A Lamia
Metformin is widely used in the treatment of type 2 diabetes to lower blood glucose. Although metformin is a relatively safe and effective drug, its clinical efficacy is variable and under certain circumstances it may contribute to life-threatening lactic acidosis. Thus, additional understanding of metformin pharmacokinetics and pharmacodynamics could provide important information regarding therapeutic use of this widely prescribed drug. Here we report a significant effect of time of day on acute blood glucose reduction in response to metformin administration and on blood lactate levels in healthy mice...
August 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28815298/the-interaction-of-pupil-response-with-the-vergence-system
#14
Moritz Feil, Barbara Moser, Mathias Abegg
PURPOSE: A gaze shift from a target at distance to a target at near leads to pupillary constriction. The regulation of this pupillary near response is ill known. We investigated the impact of accommodation, convergence, and proximity on the pupillary diameter. METHODS: We recorded pupil size and vergence eye movements with the use of an infrared eye tracker. We determined the pupillary response in four conditions: (1) after a gaze shift from far to near without accommodation, (2) after a gaze shift from far to near with neither accommodation nor convergence, (3) after accommodation alone, and (4) after accommodation with convergence without a gaze shift to near...
August 16, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28814662/irgm1-coordinately-regulates-autoimmunity-and-host-defense-at-select-mucosal-surfaces
#15
Kathleen M Azzam, Jennifer H Madenspacher, Derek W Cain, Lihua Lai, Kymberly M Gowdy, Prashant Rai, Kyathanahalli Janardhan, Natasha Clayton, Willie Cunningham, Heather Jensen, Preeyam S Patel, John F Kearney, Gregory A Taylor, Michael B Fessler
The pathogenesis of primary Sjogren's syndrome (SS), an autoimmune disease that targets the mucosa of exocrine tissues, is poorly understood. Although several mouse models have been developed that display features of SS, most of these are within the larger context of a lupus-like presentation. Immunity-related GTPase family M protein 1 (Irgm1) is an interferon-inducible cytoplasmic GTPase that is reported to regulate autophagy and mitochondrial homeostasis. Here, we report that naive Irgm1-/- mice display lymphocytic infiltration of multiple mucosal tissues including the lung in a manner reminiscent of SS, together with IgA class-predominant autoantibodies including anti-Ro and anti-La...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28814632/intermittent-apnea-elicits-inactivity-induced-phrenic-motor-facilitation-via-a-retinoic-acid-and-protein-synthesis-dependent-pathway
#16
Nathan A Baertsch, Tracy L Baker
Respiratory motoneuron pools must provide rhythmic inspiratory drive that is robust and reliable, yet dynamic enough to respond to respiratory challenges. One form of plasticity that is hypothesized to contribute to motor output stability by sensing and responding to inadequate respiratory neural activity is inactivity-induced phrenic motor facilitation (iPMF), an increase in inspiratory output triggered by a reduction in phrenic synaptic inputs. Evidence suggests that mechanisms giving rise to iPMF differ depending on the pattern of reduced respiratory neural activity (i...
August 16, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28814524/mutation-of-the-putative-immunosuppressive-domain-of-the-retroviral-envelope-glycoprotein-compromises-infectivity
#17
Urszula Eksmond, Bryony Jenkins, Julia Merkenschlager, Walther Mothes, Jonathan P Stoye, George Kassiotis
The envelope glycoprotein of diverse endogenous and exogenous retroviruses is considered inherently immunosuppressive. Extensive work mapped the immunosuppressive activity to a highly conserved domain, termed the immunosuppressive domain (ISD), in the transmembrane (TM) subunit of the envelope glycoprotein and identified two naturally polymorphic key residues that afford immunosuppressive activity to distinct envelope glycoproteins. Concurrent mutation of these two key residues (E14R and A20F) in the envelope glycoprotein of Friend murine leukemia virus (F-MLV) ISD has been reported to abolish its immunosuppressive activity, without affecting its fusogenicity, and to weaken the ability of the virus to replicate specifically in immunocompetent hosts...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814522/characterization-of-cis-acting-rna-elements-of-zika-virus-by-using-a-self-splicing-ribozyme-dependent-infectious-clone
#18
Zhong-Yu Liu, Jiu-Yang Yu, Xing-Yao Huang, Hang Fan, Xiao-Feng Li, Yong-Qiang Deng, Xue Ji, Meng-Li Cheng, Qing Ye, Hui Zhao, Jian-Feng Han, Xiao-Ping An, Tao Jiang, Bo Zhang, Yi-Gang Tong, Cheng-Feng Qin
Zika virus (ZIKV) has caused significant outbreaks and epidemics in the Americas recently, raising global concern due to its ability to cause microcephaly and other neurological complications. A stable and efficient infectious clone of ZIKV is urgently needed. However, the instability and toxicity of flavivirus cDNA clones in E. coli hosts has hindered the development of ZIKV infectious clones. Herein, using a novel self-splicing ribozyme-based strategy, we have generated a stable infectious cDNA clone of a contemporary ZIKV strain imported from Venezuela to China in 2016...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28814518/a-single-amino-acid-substitution-at-position-225-in-ha-alters-the-transmissibility-of-eurasian-avian-like-h1n1-swine-influenza-virus-in-guinea-pigs
#19
Zeng Wang, Huanliang Yang, Yan Chen, Shiyu Tao, Liling Liu, Huihui Kong, Shujie Ma, Fei Meng, Yasuo Suzuki, Chuanling Qiao, Hualan Chen
Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28813663/a-crispr-activation-screen-identifies-a-pan-avian-influenza-virus-inhibitory-host-factor
#20
Brook E Heaton, Edward M Kennedy, Rebekah E Dumm, Alfred T Harding, Matthew T Sacco, David Sachs, Nicholas S Heaton
Influenza A virus (IAV) is a pathogen that poses significant risks to human health. It is therefore critical to develop strategies to prevent influenza disease. Many loss-of-function screens have been performed to identify the host proteins required for viral infection. However, there has been no systematic screen to identify the host factors that, when overexpressed, are sufficient to prevent infection. In this study, we used CRISPR/dCas9 activation technology to perform a genome-wide overexpression screen to identify IAV restriction factors...
August 15, 2017: Cell Reports
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