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  • 1
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    TRPC channel activation by extracellular thioredoxin (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-01-04
    Description: Mammalian homologues of Drosophila melanogaster transient receptor potential (TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor. Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 (canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion-selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown. Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis, an inflammatory joint disease that disables millions of people worldwide. We show that TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion-channel activation mechanism that couples extracellular thioredoxin to cell function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645077/" 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/PMC2645077/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Xu, Shang-Zhong -- Sukumar, Piruthivi -- Zeng, Fanning -- Li, Jing -- Jairaman, Amit -- English, Anne -- Naylor, Jacqueline -- Ciurtin, Coziana -- Majeed, Yasser -- Milligan, Carol J -- Bahnasi, Yahya M -- Al-Shawaf, Eman -- Porter, Karen E -- Jiang, Lin-Hua -- Emery, Paul -- Sivaprasadarao, Asipu -- Beech, David J -- 077424/Wellcome Trust/United Kingdom -- 083857/Wellcome Trust/United Kingdom -- 18475/Arthritis Research UK/United Kingdom -- BB/D524875/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2008 Jan 3;451(7174):69-72. doi: 10.1038/nature06414.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Membrane and Systems Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18172497" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis, Rheumatoid/metabolism/pathology ; Cell Line ; Disulfides/chemistry/metabolism ; Electric Conductivity ; Humans ; Oxidation-Reduction/drug effects ; Patch-Clamp Techniques ; Rabbits ; TRPC Cation Channels/*agonists/chemistry/*metabolism ; Thioredoxins/chemistry/*pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 2
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    Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-09-18
    Description: The stability of the Wnt pathway transcription factor beta-catenin is tightly regulated by the multi-subunit destruction complex. Deregulated Wnt pathway activity has been implicated in many cancers, making this pathway an attractive target for anticancer therapies. However, the development of targeted Wnt pathway inhibitors has been hampered by the limited number of pathway components that are amenable to small molecule inhibition. Here, we used a chemical genetic screen to identify a small molecule, XAV939, which selectively inhibits beta-catenin-mediated transcription. XAV939 stimulates beta-catenin degradation by stabilizing axin, the concentration-limiting component of the destruction complex. Using a quantitative chemical proteomic approach, we discovered that XAV939 stabilizes axin by inhibiting the poly-ADP-ribosylating enzymes tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Thus, our study provides new mechanistic insights into the regulation of axin protein homeostasis and presents new avenues for targeted Wnt pathway therapies.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Shih-Min A -- Mishina, Yuji M -- Liu, Shanming -- Cheung, Atwood -- Stegmeier, Frank -- Michaud, Gregory A -- Charlat, Olga -- Wiellette, Elizabeth -- Zhang, Yue -- Wiessner, Stephanie -- Hild, Marc -- Shi, Xiaoying -- Wilson, Christopher J -- Mickanin, Craig -- Myer, Vic -- Fazal, Aleem -- Tomlinson, Ronald -- Serluca, Fabrizio -- Shao, Wenlin -- Cheng, Hong -- Shultz, Michael -- Rau, Christina -- Schirle, Markus -- Schlegl, Judith -- Ghidelli, Sonja -- Fawell, Stephen -- Lu, Chris -- Curtis, Daniel -- Kirschner, Marc W -- Lengauer, Christoph -- Finan, Peter M -- Tallarico, John A -- Bouwmeester, Tewis -- Porter, Jeffery A -- Bauer, Andreas -- Cong, Feng -- England -- Nature. 2009 Oct 1;461(7264):614-20. doi: 10.1038/nature08356. Epub 2009 Sep 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759537" target="_blank"〉PubMed〈/a〉
    Keywords: Axin Protein ; Cell Division/drug effects ; Cell Line ; Cell Line, Tumor ; Colorectal Neoplasms/drug therapy/metabolism ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Proteasome Endopeptidase Complex/metabolism ; Protein Binding ; Proteomics ; Repressor Proteins/chemistry/*metabolism ; Signal Transduction/*drug effects ; Tankyrases/*antagonists & inhibitors/metabolism ; Transcription, Genetic/drug effects ; Ubiquitin/metabolism ; Ubiquitination ; Wnt Proteins/*antagonists & inhibitors/metabolism ; beta Catenin/antagonists & inhibitors/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    QBO as Potential Amplifier of Solar Cycle Influence (2006)
    In:  Other Sources
    Details
    Publication Date: 2018-06-06
    Description: The solar cycle (SC) effect in the lower atmosphere has been linked observationally to the quasi-biennial oscillation (QBO) of the zonal circulation. Salby and Callaghan (2000) in particular analyzed the QBO covering more than 40 years and found that it contains a large SC signature at 20 km. We discuss a 3D study in which we simulate the QBO under the influence of the SC. For a SC period of 10 years, the relative amplitude of radiative forcing is taken to vary with height: 0.2% (surface), 2% (50 km), 20% (100 km and above). This model produces in the lower stratosphere a relatively large modulation of the QBO, which appears to come from the SC and qualitatively agrees with the observations. The modulation of the QBO, with constant phase relative to the SC, is shown to persist at least for 50 years, and it is induced by a SC modulated annual oscillation that is hemispherically symmetric and confined to low latitudes.
    Keywords: Solar Physics
    Type: Geophysical Research Letters; Volume 33
    Format: text
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  • 4
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    The Solar Ultraviolet Magnetograph Investigation: Polarization Properties (2005)
    In:  Other Sources
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    Publication Date: 2019-07-18
    Description: This paper will describe the objectives of the Marshall Space Flight Center (MSFC) Solar Ultraviolet Magnetograph Investigation (SUMI) and the optical components that have been developed to meet those objectives. A sounding rocket payload is being developed to test the feasibility of magnetic field measurements in the Sun s transition region. This paper will review the scientific measurements that will be made by the SUMI sounding rocket program, and the optics have been optimized for simultaneous measurements of two magnetic lines formed in the transition region (CIV at 1550 A and MgII at 2800 A). Finally, this paper will concentrate on the polarization properties of the SUM1 polarimeter and toroidal varied-line-space gratings.
    Keywords: Solar Physics
    Type: SPIE Optics and Photonics; Jul 31, 2005 - Aug 04, 2005; San Diego, CA; United States
    Format: text
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  • 5
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    The Sheath Transport Observer for the Redistribution of Mass (STORM) Image (2008)
    In:  Other Sources
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    Publication Date: 2019-07-19
    Description: All of the solar wind energy that powers magnetospheric processes passes through the magnetosheath and magnetopause. Global images of the magnetosheath and magnetopause boundary layers will resolve longstanding controversy surrounding fundamental phenomena that occur at the magnetopause and provide information needed to improve operational space weather models. Recent developments showing that soft X-rays (0.15-1 keV) result from high charge state solar wind ions undergoing charge exchange recombination through collisions with exospheric neutral atoms has led to the realization that soft X-ray imaging can provide global maps of the high-density shocked solar wind within the magnetosheath and cusps, regions lying between the lower density solar wind and magnetosphere. We discuss an instrument concept called the Sheath Transport Observer for the Redistribution of Mass (STORM), an X-ray imager suitable for simultaneously imaging the dayside magnetosheath, the magnetopause boundary layers, and the cusps.
    Keywords: Solar Physics
    Type: American Geophysical Union Conference; Dec 11, 2008 - Dec 20, 2008; San Francisco, CA; United States
    Format: text
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