Attenuation of Macrophage Migration Inhibitory Factor-Stimulated Signaling via S-Nitrosylation.
Biol Pharm Bull
; 42(6): 1044-1047, 2019.
Article
em En
| MEDLINE
| ID: mdl-31155581
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores Inibidores da Migração de Macrófagos
/
Doadores de Óxido Nítrico
/
Cisteína
/
S-Nitrosotióis
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biol Pharm Bull
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article