Methionine sulfoxide reductase A negatively controls microglia-mediated neuroinflammation via inhibiting ROS/MAPKs/NF-κB signaling pathways through a catalytic antioxidant function.
Antioxid Redox Signal
; 22(10): 832-47, 2015 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-25602783
ABSTRACT
AIMS:
Oxidative burst is one of the earliest biochemical events in the inflammatory activation of microglia. Here, we investigated the potential role of methionine sulfoxide reductase A (MsrA), a key antioxidant enzyme, in the control of microglia-mediated neuroinflammation.RESULTS:
MsrA was detected in rat microglia and its expression was upregulated on microglial activation. Silencing of MsrA exacerbated lipopolysaccharide (LPS)-induced activation of microglia and the production of inflammatory markers, indicating that MsrA may function as an endogenous protective mechanism for limiting uncontrolled neuroinflammation. Application of exogenous MsrA by transducing Tat-rMsrA fusion protein into microglia attenuated LPS-induced neuroinflammatory events, which was indicated by an increased Iba1 (a specific microglial marker) expression and the secretion of pro-inflammatory cytokines, and this attenuation was accompanied by inhibiting multiple signaling pathways such as p38 and ERK mitogen-activated protein kinases (MAPKs) and nuclear factor kappaB (NF-κB). These effects were due to MsrA-mediated reactive oxygen species (ROS) elimination, which may be derived from a catalytic effect of MsrA on the reaction of methionine with ROS. Furthermore, the transduction of Tat-rMsrA fusion protein suppressed the activation of microglia and the expression of pro-inflammatory factors in a rat model of neuroinflammation in vivo. INNOVATION This study provides the first direct evidence for the biological significance of MsrA in microglia-mediated neuroinflammation.CONCLUSION:
Our data provide a profound insight into the role of endogenous antioxidative defense systems such as MsrA in the control of microglial function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
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Proteínas Proto-Oncogênicas
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Receptores Proteína Tirosina Quinases
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Microglia
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Metionina Sulfóxido Redutases
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Inflamação
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Proteínas dos Microfilamentos
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Antioxidantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article