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Enhanced phosphatidylinositol 4-phosphate 5-kinase alpha expression and PI(4,5)P2 production in LPS-stimulated microglia.

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dc.contributor.authorLee, SY-
dc.contributor.authorKim, B-
dc.contributor.authorJeong, HK-
dc.contributor.authorMin, KJ-
dc.contributor.authorLiu, T-
dc.contributor.authorPark, JY-
dc.contributor.authorJoe, EH-
dc.contributor.authorJou, I-
dc.date.accessioned2011-05-31T05:44:47Z-
dc.date.available2011-05-31T05:44:47Z-
dc.date.issued2010-
dc.identifier.issn0197-0186-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/2761-
dc.description.abstractMicroglia are the major glial cells responsible for immune responses against harmful substances in the central nervous system. Type I phosphatidylinositol 4-phosphate 5-kinase alpha (PIP5Kalpha) and its lipid product, phosphatidylinositol 4,5-bisphosphate (PI[4,5]P(2)), regulate important cell surface functions. Here, we report that lipopolysaccharide (LPS) significantly enhanced PIP5Kalpha mRNA and protein expression levels in a time- and concentration-dependent manner in microglia. Furthermore, LPS stimulation led to a robust increase in PI(4,5)P(2) in the plasma membrane, demonstrated by PI(4,5)P(2) immunostaining or PI(4,5)P(2) imaging using a PI(4,5)P(2)-specific probe, tubby (R332H), fused to yellow fluorescent protein. Phosphatidylinositol 3-kinase, p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and c-Jun N-terminal kinase signaling pathway inhibitors clearly reduced PIP5Kalpha expression, indicating that these pathways are necessary for LPS-induced PIP5Kalpha expression. In addition, inhibition of nuclear factor-kappaB and Sp1 transcription factors interfered with the LPS-induced upregulation of PIP5Kalpha. Delivery of PI(4,5)P(2) into microglia increased the expression of interleukin-1beta and tumor necrosis factor alpha. These findings indicate that PIP5Kalpha upregulation and the subsequent rise in PI(4,5)P(2) in LPS-stimulated microglia may positively regulate microglial inflammatory responses.-
dc.language.isoen-
dc.subject.MESHAnimals-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCell Line-
dc.subject.MESHCytokines-
dc.subject.MESHFluorescent Antibody Technique-
dc.subject.MESHLipopolysaccharides-
dc.subject.MESHMacrophage Activation-
dc.subject.MESHMice-
dc.subject.MESHMicroglia-
dc.subject.MESHMicroscopy, Confocal-
dc.subject.MESHNF-kappa B-
dc.subject.MESHPhosphatidylinositol 4,5-Diphosphate-
dc.subject.MESHPhosphotransferases (Alcohol Group Acceptor)-
dc.subject.MESHReverse Transcriptase Polymerase Chain Reaction-
dc.subject.MESHStimulation, Chemical-
dc.subject.MESHTransfection-
dc.titleEnhanced phosphatidylinositol 4-phosphate 5-kinase alpha expression and PI(4,5)P2 production in LPS-stimulated microglia.-
dc.typeArticle-
dc.identifier.pmid20659513-
dc.identifier.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0197-0186(10)00234-2-
dc.contributor.affiliatedAuthor이, 상윤-
dc.contributor.affiliatedAuthor조, 은혜-
dc.contributor.affiliatedAuthor주, 일로-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.neuint.2010.07.008-
dc.citation.titleNeurochemistry international-
dc.citation.volume57-
dc.citation.number5-
dc.citation.date2010-
dc.citation.startPage600-
dc.citation.endPage607-
dc.identifier.bibliographicCitationNeurochemistry international, 57(5). : 600-607, 2010-
dc.identifier.eissn1872-9754-
dc.relation.journalidJ001970186-
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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