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

Authors
Lee, SY  | Kim, B | Jeong, HK | Min, KJ | Liu, T | Park, JY | Joe, EH  | Jou, I
Citation
Neurochemistry international, 57(5). : 600-607, 2010
Journal Title
Neurochemistry international
ISSN
0197-01861872-9754
Abstract
Microglia 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.
MeSH

DOI
10.1016/j.neuint.2010.07.008
PMID
20659513
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
이, 상윤  |  조, 은혜  |  주, 일로
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