Phosphatidylinositol 4-phosphate 5-kinase alpha is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses
Experimental & Molecular Medicine
; : 662-673, 2010.
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| ID: wpr-162251
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WPRO
ABSTRACT
In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5Kalpha) that is responsible for production of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) regulates many important cell functions at the cell surface. Here, we have examined whether PIP5Kalpha is associated with astrocyte inflammatory responses. Gangliosides are releasable from damaged cell membranes of neurons and capable of inducing inflammatory responses. We found that treatment of primary cultured astrocytes with gangliosides significantly enhanced PIP5Kalpha mRNA and protein expression levels. PI(4,5)P2 imaging using a fluorescent tubby (R332H) expression as a PI(4,5)P2-specific probe showed that ganglioside treatment increased PI(4,5)P2 level. Interestingly, microRNA-based PIP5Kalpha knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1beta and TNFalpha. PIP5Kalpha knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-kappaB and the degradation of IkappaB-alpha, indicating that PIP5Kalpha knockdown interfered with the ganglioside-activated NF-kappaB signaling. Together, these results suggest that PIP5Kalpha is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-kappaB activation in ganglioside-stimulated astrocytes.
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Assunto principal:
RNA Mensageiro
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Transdução de Sinais
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Regulação para Cima
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Células Cultivadas
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Astrócitos
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NF-kappa B
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Interleucina-1
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Fator de Necrose Tumoral alfa
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Ratos Sprague-Dawley
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Fosfotransferases (Aceptor do Grupo Álcool)
Limite:
Animals
Idioma:
En
Revista:
Experimental & Molecular Medicine
Ano de publicação:
2010
Tipo de documento:
Article