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  • 1
    Publication Date: 2014-08-15
    Description: The LRRK2 inhibitor GSK2578215A induces protective autophagy in SH-SY5Y cells: involvement of Drp-1-mediated mitochondrial fission and mitochondrial-derived ROS signaling Cell Death and Disease 5, e1368 (August 2014). doi:10.1038/cddis.2014.320 Authors: S Saez-Atienzar, L Bonet-Ponce, J R Blesa, F J Romero, M P Murphy, J Jordan & M F Galindo
    Electronic ISSN: 2041-4889
    Topics: Biology , Medicine
    Published by Springer Nature
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  • 2
    Publication Date: 2001-10-27
    Description: ErbB-4 is a transmembrane receptor tyrosine kinase that regulates cell proliferation and differentiation. After binding of its ligand heregulin (HRG) or activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate (TPA), the ErbB-4 ectodomain is cleaved by a metalloprotease. We now report a subsequent cleavage by gamma-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus. gamma-Secretase cleavage was prevented by chemical inhibitors or a dominant negative presenilin. Inhibition of gamma-secretase also prevented growth inhibition by HRG. gamma-Secretase cleavage of ErbB-4 may represent another mechanism for receptor tyrosine kinase-mediated signaling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ni, C Y -- Murphy, M P -- Golde, T E -- Carpenter, G -- CA24071/CA/NCI NIH HHS/ -- CA68485/CA/NCI NIH HHS/ -- DK20593/DK/NIDDK NIH HHS/ -- NS39072/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2001 Dec 7;294(5549):2179-81. Epub 2001 Oct 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11679632" target="_blank"〉PubMed〈/a〉
    Keywords: Active Transport, Cell Nucleus ; Amino Acid Sequence ; Amyloid Precursor Protein Secretases ; Animals ; Aspartic Acid Endopeptidases ; COS Cells ; Carbamates/pharmacology ; Cell Division/drug effects ; Cell Line ; Cell Membrane/metabolism ; Cell Nucleus/*metabolism ; Cytoplasm/metabolism ; Dipeptides/pharmacology ; Endopeptidases/*metabolism ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Membrane Proteins/genetics/metabolism ; Metalloendopeptidases/metabolism ; Mice ; Molecular Sequence Data ; Mutation ; Neuregulin-1/pharmacology ; Presenilin-1 ; Protease Inhibitors/pharmacology ; Protein Structure, Tertiary ; Receptor, Epidermal Growth Factor/chemistry/*metabolism ; Receptor, ErbB-4 ; Recombinant Fusion Proteins/metabolism ; Signal Transduction ; Tetradecanoylphorbol Acetate/pharmacology ; Transcriptional Activation ; Tumor Cells, Cultured
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2010-10-12
    Description: Blood pressure is critically controlled by angiotensins, which are vasopressor peptides specifically released by the enzyme renin from the tail of angiotensinogen-a non-inhibitory member of the serpin family of protease inhibitors. Although angiotensinogen has long been regarded as a passive substrate, the crystal structures solved here to 2.1 A resolution show that the angiotensin cleavage site is inaccessibly buried in its amino-terminal tail. The conformational rearrangement that makes this site accessible for proteolysis is revealed in our 4.4 A structure of the complex of human angiotensinogen with renin. The co-ordinated changes involved are seen to be critically linked by a conserved but labile disulphide bridge. Here we show that the reduced unbridged form of angiotensinogen is present in the circulation in a near 40:60 ratio with the oxidized sulphydryl-bridged form, which preferentially interacts with receptor-bound renin. We propose that this redox-responsive transition of angiotensinogen to a form that will more effectively release angiotensin at a cellular level contributes to the modulation of blood pressure. Specifically, we demonstrate the oxidative switch of angiotensinogen to its more active sulphydryl-bridged form in the maternal circulation in pre-eclampsia-the hypertensive crisis of pregnancy that threatens the health and survival of both mother and child.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024006/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Aiwu -- Carrell, Robin W -- Murphy, Michael P -- Wei, Zhenquan -- Yan, Yahui -- Stanley, Peter L D -- Stein, Penelope E -- Broughton Pipkin, Fiona -- Read, Randy J -- 082961/Wellcome Trust/United Kingdom -- BS/05/002/18361/British Heart Foundation/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- PG/08/041/24818/British Heart Foundation/United Kingdom -- PG/09/072/27945/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2010 Nov 4;468(7320):108-11. doi: 10.1038/nature09505. Epub 2010 Oct 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK. awz20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20927107" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Angiotensinogen/blood/*chemistry/*metabolism ; Angiotensins/chemistry/*metabolism/secretion ; Blood Pressure ; Crystallography, X-Ray ; Disulfides/chemistry/metabolism ; Female ; Humans ; Kinetics ; Models, Molecular ; Molecular Sequence Data ; Oxidation-Reduction ; Oxidative Stress ; Pre-Eclampsia/blood/metabolism ; Pregnancy ; Protein Conformation ; *Protein Processing, Post-Translational ; Renin/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-11-11
    Description: Ischaemia-reperfusion injury occurs when the blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death and aberrant immune responses through the generation of mitochondrial reactive oxygen species (ROS). Although mitochondrial ROS production in ischaemia reperfusion is established, it has generally been considered a nonspecific response to reperfusion. Here we develop a comparative in vivo metabolomic analysis, and unexpectedly identify widely conserved metabolic pathways responsible for mitochondrial ROS production during ischaemia reperfusion. We show that selective accumulation of the citric acid cycle intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase, which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. After reperfusion, the accumulated succinate is rapidly re-oxidized by succinate dehydrogenase, driving extensive ROS generation by reverse electron transport at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo ischaemia-reperfusion injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of ischaemia-reperfusion injury. Furthermore, these findings reveal a new pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation after subsequent reperfusion is a potential therapeutic target to decrease ischaemia-reperfusion injury in a range of pathologies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255242/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255242/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chouchani, Edward T -- Pell, Victoria R -- Gaude, Edoardo -- Aksentijevic, Dunja -- Sundier, Stephanie Y -- Robb, Ellen L -- Logan, Angela -- Nadtochiy, Sergiy M -- Ord, Emily N J -- Smith, Anthony C -- Eyassu, Filmon -- Shirley, Rachel -- Hu, Chou-Hui -- Dare, Anna J -- James, Andrew M -- Rogatti, Sebastian -- Hartley, Richard C -- Eaton, Simon -- Costa, Ana S H -- Brookes, Paul S -- Davidson, Sean M -- Duchen, Michael R -- Saeb-Parsy, Kourosh -- Shattock, Michael J -- Robinson, Alan J -- Work, Lorraine M -- Frezza, Christian -- Krieg, Thomas -- Murphy, Michael P -- G1100562/Medical Research Council/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- MC_U105674181/Medical Research Council/United Kingdom -- MC_UP_1101/3/Medical Research Council/United Kingdom -- MC_UU_12022/6/Medical Research Council/United Kingdom -- PG/07/126/24223/British Heart Foundation/United Kingdom -- PG/12/42/29655/British Heart Foundation/United Kingdom -- R01 HL071158/HL/NHLBI NIH HHS/ -- RG/12/4/29426/British Heart Foundation/United Kingdom -- British Heart Foundation/United Kingdom -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- England -- Nature. 2014 Nov 20;515(7527):431-5. doi: 10.1038/nature13909. Epub 2014 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK [2] Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. ; Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. ; MRC Cancer Unit, University of Cambridge, Hutchison/MRC Research Centre, Box 197, Cambridge Biomedical Campus, Cambridge CB2 0XZ, UK. ; King's College London, British Heart Foundation Centre of Research Excellence, The Rayne Institute, St Thomas' Hospital, London SE1 7EH, UK. ; Department of Cell and Developmental Biology and UCL Consortium for Mitochondrial Biology, University College London, Gower Street, London WC1E 6BT, UK. ; MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK. ; Department of Anesthesiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, New York 14642, USA. ; Institute of Cardiovascular &Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. ; School of Chemistry, University of Glasgow, Glasgow G12 8QQ, UK. ; Unit of Paediatric Surgery, UCL Institute of Child Health, London WC1N 1EH, UK. ; Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London WC1E 6HX, UK. ; University Department of Surgery and Cambridge NIHR Biomedical Research Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25383517" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Monophosphate/metabolism ; Animals ; Aspartic Acid/metabolism ; Citric Acid Cycle ; Disease Models, Animal ; Electron Transport ; Electron Transport Complex I/metabolism ; Fumarates/metabolism ; Ischemia/enzymology/*metabolism ; Malates/metabolism ; Male ; Metabolomics ; Mice ; Mitochondria/enzymology/*metabolism ; Myocardial Infarction/enzymology/metabolism ; Myocardium/cytology/enzymology/metabolism ; Myocytes, Cardiac/enzymology/metabolism ; NAD/metabolism ; Reactive Oxygen Species/*metabolism ; Reperfusion Injury/enzymology/*metabolism ; Stroke/enzymology/metabolism ; Succinate Dehydrogenase/metabolism ; Succinic Acid/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2014-10-25
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346172/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346172/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schwarzlander, Markus -- Wagner, Stephan -- Ermakova, Yulia G -- Belousov, Vsevolod V -- Radi, Rafael -- Beckman, Joseph S -- Buettner, Garry R -- Demaurex, Nicolas -- Duchen, Michael R -- Forman, Henry J -- Fricker, Mark D -- Gems, David -- Halestrap, Andrew P -- Halliwell, Barry -- Jakob, Ursula -- Johnston, Iain G -- Jones, Nick S -- Logan, David C -- Morgan, Bruce -- Muller, Florian L -- Nicholls, David G -- Remington, S James -- Schumacker, Paul T -- Winterbourn, Christine C -- Sweetlove, Lee J -- Meyer, Andreas J -- Dick, Tobias P -- Murphy, Michael P -- 098565/Wellcome Trust/United Kingdom -- MC_U105663142/Medical Research Council/United Kingdom -- P30 CA086862/CA/NCI NIH HHS/ -- P30 ES005605/ES/NIEHS NIH HHS/ -- R01 AG027349/AG/NIA NIH HHS/ -- R01 CA169046/CA/NCI NIH HHS/ -- R01 GM073929/GM/NIGMS NIH HHS/ -- R21 AG046799/AG/NIA NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):E12-4. doi: 10.1038/nature13858.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Crop Science and Resource Conservation (INRES), University of Bonn, Friedrich-Ebert-Allee 144, 53113 Bonn, Germany. ; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia. ; Departamento de Bioquimica, and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la Republica, Avda. General Flores 2125, 11800 Montevideo, Uruguay. ; Linus Pauling Institute, Environmental Health Sciences Center, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA. ; The University of Iowa, Department of Radiation Oncology and Interdisciplinary Graduate Program in Human Toxicology, and ESR Facility, College of Medicine, Med Labs B180K, Iowa City, Iowa 52242-1181, USA. ; Department of Cell Physiology and Metabolism, University of Geneva, 1, rue Michel-Servet, Geneva 4 CH-1211, Switzerland. ; Department of Cell and Developmental Biology and Consortium for Mitochondrial Research, University College London, Gower Street, London WC1E 6BT, UK. ; 1] Life and Environmental Sciences Unit, University of California, Merced, 5200 North Lake Road, Merced, California 95344, USA [2] Andrus Gerontology Center of the Davis School of Gerontology, University of Southern California, 3715 McClintock Avenue, Los Angeles, California 90089-0191, USA. ; Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK. ; Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. ; School of Biochemistry and Bristol CardioVascular, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD, UK. ; Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore. ; Molecular, Cellular and Developmental Biology Department, University of Michigan, Ann Arbor, Michigan 48109-1048, USA. ; Department of Mathematics, South Kensington Campus, Imperial College London, London SW7 2AZ, UK. ; Universite d'Angers &INRA &Agrocampus Ouest, UMR 1345 Institut de Recherche en Horticulture et Semences, Angers, F-49045, France. ; Division of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. ; Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. ; Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, California 94945, USA. ; Department of Physics, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229, USA. ; Department of Pediatrics, Division of Neonatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, 60611, USA. ; Centre for Free Radical Research, Department of Pathology, University of Otago, ChristchurchPO Box 4345, Christchurch, New Zealand. ; MRC Mitochondrial Biology Unit, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25341790" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Caenorhabditis elegans/*metabolism ; *Longevity ; Male ; Mitochondria/*metabolism ; Superoxides/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    Chicago : Periodicals Archive Online (PAO)
    Journal of marketing research. 2:3 (1965:Aug.) 307 
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  • 7
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt) encoding tau protein cause frontotemporal dementia ...
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2003-04-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 9
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