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Phosphatidylinositol 4-phosphate 5-kinase alpha is induced in ganglioside-stimulated brain astrocytes and contributes to inflammatory responses.

Lee, SY; Kim, B; Yoon, S; Kim, YJ; Liu, T; Woo, JH; Chwae, YJ; Joe, EH; Jou, I
Experimental & molecular medicine, 42(9):662-673, 2010
Journal Title
Experimental & molecular medicine
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 (PIP5K alpha) 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 PIP5K alpha 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 PIP5K alpha 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 PIP5K alpha knockdown strongly reduced ganglioside-induced transcription of proinflammatory cytokines IL-1 beta and TNFalpha. PIP5K alpha knockdown also suppressed ganglioside-induced phosphorylation and nuclear translocation of NF-kappaB and the degradation of I kappaB-alpha, indicating that PIP5K alpha knockdown interfered with the ganglioside-activated NF-kappaB signaling. Together, these results suggest that PIP5K alpha is a novel inflammatory mediator that undergoes upregulation and contributes to immune responses by facilitating NF-kappaB activation in ganglioside-stimulated astrocytes.
MeSH terms
AnimalsAstrocytes/*metabolismCells, CulturedGangliosides/*metabolismGene Knockdown TechniquesInflammation/*metabolismInterleukin-1/metabolismNF-kappa B/metabolismPhosphotransferases (Alcohol Group Acceptor)/*metabolismRNA, Messenger/*genetics/metabolismRatsRats, Sprague-DawleySignal TransductionTumor Necrosis Factor-alpha/metabolismUp-Regulation
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
이, 상윤윤, 사라우, 주홍최, 용준조, 은혜주, 일로
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