Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling via S-Nitrosylation

Kengo Nakahara, Kana Fujikawa, Hideki Hiraoka, Ikuko Miyazaki, Masato Asanuma, Akihiro Ito, Nobumasa Takasugi, Takashi Uehara

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Nitric oxide (NO) is a key signaling molecule that has various effects via S-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 S-nitrosylated by a physiological NO donor. Interestingly, the induction of S-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.

Original languageEnglish
Pages (from-to)1044-1047
Number of pages4
JournalBiological & pharmaceutical bulletin
Volume42
Issue number6
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Macrophage Migration-Inhibitory Factors
Brain-Derived Neurotrophic Factor
p38 Mitogen-Activated Protein Kinases
Nitric Oxide Donors
Post Translational Protein Processing
Neurodegenerative Diseases
Parkinson Disease
Alzheimer Disease
Nitric Oxide
Ligands
Gene Expression
Neurons
Proteins

Keywords

  • brain
  • macrophage migration inhibitory factor
  • nitric oxide
  • S-nitrosylation

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling via S-Nitrosylation. / Nakahara, Kengo; Fujikawa, Kana; Hiraoka, Hideki; Miyazaki, Ikuko; Asanuma, Masato; Ito, Akihiro; Takasugi, Nobumasa; Uehara, Takashi.

In: Biological & pharmaceutical bulletin, Vol. 42, No. 6, 01.01.2019, p. 1044-1047.

Research output: Contribution to journalArticle

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