WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1.

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  • Author(s): Wang S;Wang S; Chong ZZ; Shang YC; Maiese K
  • Source:
    Current neurovascular research [Curr Neurovasc Res] 2013 Feb; Vol. 10 (1), pp. 54-69.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 101208439 Publication Model: Print Cited Medium: Internet ISSN: 1875-5739 (Electronic) Linking ISSN: 15672026 NLM ISO Abbreviation: Curr Neurovasc Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Saif Zone, Sharjah, U.A.E. ; San Francisco, CA : Bentham Science Publishers, c2004-
    • Subject Terms:
      CCN Intercellular Signaling Proteins/*pharmacology ; Forkhead Transcription Factors/*metabolism ; Hippocampus/*metabolism ; Homeostasis/*physiology ; Neurons/*metabolism ; Proto-Oncogene Proteins/*pharmacology ; Signal Transduction/*physiology ; Sirtuin 1/*metabolism; Androstadienes/pharmacology ; Caspase 3/genetics ; Caspase 3/metabolism ; Cell Hypoxia ; Cell Survival/drug effects ; Cell Survival/physiology ; Chromones/pharmacology ; Enzyme Inhibitors/pharmacology ; Forkhead Box Protein O3 ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Hippocampus/drug effects ; Homeostasis/drug effects ; Humans ; Morpholines/pharmacology ; Neurons/drug effects ; Oxidative Stress/physiology ; Phosphorylation/drug effects ; Resveratrol ; Signal Transduction/drug effects ; Stilbenes/pharmacology ; Wortmannin
    • Abstract:
      As a member of the secreted extracellular matrix associated proteins of the CCN family, Wnt1 inducible signaling pathway protein 1 (WISP1/CCN4) is garnering increased attention not only as a potent proliferative entity, but also as a robust cytoprotective agent during toxic insults. Here we demonstrate that WISP1 prevents forkhead transcription factor FoxO3a mediated caspase 1 and caspase 3 apoptotic cell death in primary neurons during oxidant stress. Phosphoinositide 3-kinase (PI 3-K) and protein kinase B (Akt1) are necessary for WISP1 to foster posttranslational phosphorylation of FoxO3a and sequester FoxO3a in the cytoplasm of neurons with protein 14-3-3. Through an autoregulatory loop, WISP1 also minimizes deacytelation of FoxO3a, prevents caspase 1 and 3 activation, and promotes an effective neuroprotective level of SIRT1 activity through SIRT1 nuclear trafficking and prevention of SIRT1 caspase degradation. Elucidation of the critical pathways of WISP1 that determine neuronal cell survival during oxidative stress may offer novel therapeutic avenues for neurodegenerative disorders.
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    • Grant Information:
      R01 NS053946 United States NS NINDS NIH HHS
    • Accession Number:
      0 (Androstadienes)
      0 (CCN Intercellular Signaling Proteins)
      0 (CCN4 protein, human)
      0 (Chromones)
      0 (Enzyme Inhibitors)
      0 (FOXO3 protein, rat)
      0 (Forkhead Box Protein O3)
      0 (Forkhead Transcription Factors)
      0 (Heterocyclic Compounds, 4 or More Rings)
      0 (Morpholines)
      0 (Proto-Oncogene Proteins)
      0 (SRT1720)
      0 (Stilbenes)
      31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
      EC 3.4.22.- (Caspase 3)
      EC 3.5.1.- (Sirt1 protein, rat)
      EC 3.5.1.- (Sirtuin 1)
      Q369O8926L (Resveratrol)
      XVA4O219QW (Wortmannin)
    • Publication Date:
      Date Created: 20121116 Date Completed: 20130729 Latest Revision: 20211021
    • Publication Date:
      20221213
    • Accession Number:
      PMC3568221
    • Accession Number:
      10.2174/156720213804805945
    • Accession Number:
      23151077