Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling <i>via</i> <i>S</i>-Nitrosylation

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Author(s)

Abstract

<p>Nitric oxide (NO) is a key signaling molecule that has various effects <i>via</i> <i>S</i>-nitrosylation, a reversible post-translational modification that affects the enzymatic activity, localization, and metabolism of target proteins. As chronic nitrosative stress correlates with neurodegeneration, the targets have received focused attention. Macrophage migration inhibitory factor (MIF) plays a pivotal role in the induction of gene expression to control inflammatory responses. MIF acts as a ligand for CD74 receptor and activates the Src-p38 mitogen-activated protein kinase (MAPK) cascade. MIF also elevates the expression of brain-derived neurotrophic factor (BDNF), which contributes to the viability of neurons. Here, we show that MIF is <i>S</i>-nitrosylated by a physiological NO donor. Interestingly, the induction of <i>S</i>-nitrosylation resulted in a loss of MIF activity following stimulation of the Src and p38 MAPK signaling pathways and the induction of BDNF expression. Our results shed light on the pathogenic mechanisms of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.</p>

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 42(6), 1044-1047, 2019

    The Pharmaceutical Society of Japan

Codes

  • NII Article ID (NAID)
    130007657685
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • ISSN
    0918-6158
  • NDL Article ID
    029698610
  • NDL Call No.
    Z53-V41
  • Data Source
    NDL  J-STAGE 
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