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Gangliosides activate microglia via protein kinase C and NADPH oxidase.

Authors
Min, KJ; Pyo, HK; Yang, MS; Ji, KA; Jou, I; Joe, EH
Citation
Glia, 48(3):197-206, 2004
Journal Title
Glia
ISSN
0894-14911098-1136
Abstract
Microglia, the major immune effector cells in the central nervous system, are activated when the brain suffers injury. A number of studies indicate that gangliosides activate microglia. However, the signaling mechanisms involved in microglial activation are not yet to be elucidated. Our results show that gangliosides induce the expression of interleukin (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in rat brain microglia and BV2 murine microglia via protein kinase C (PKC) and NADPH oxidase. Expression of IL-1beta, TNF-alpha, and iNOS in ganglioside-treated cells was significantly reduced in the presence of inhibitors of PKC (GF109203X, Go6976, Ro31-8220, and rottlerin) and NADPH oxidase (diphenyleneiodonium chloride [DPI]). In response to gangliosides, PKC-alpha, betaII, and delta and NADPH oxidase p67(phox) translocated from the cytosol to the membrane. ROS generation was also activated within 5 min of ganglioside treatment. Ganglioside-induced ROS generation was blocked by PKC inhibitors. Furthermore, ganglioside-induced activation of NF-kappaB, an essential transcription factor that mediates the expression of IL-1beta, TNF-alpha, and iNOS, was reduced in the presence of GF109203X and DPI. Our results collectively suggest that gangliosides activate microglia via PKC and NADPH oxidase, which regulate activation of NF-kappaB.
MeSH terms
AnimalsCell LineCells, CulturedCentral Nervous System/cytology/*enzymologyEncephalitis/*enzymology/physiopathologyEnzyme Inhibitors/pharmacologyGangliosides/*metabolism/pharmacologyInterleukin-1/metabolismIsoenzymes/drug effects/metabolismMiceMicroglia/cytology/drug effects/*enzymologyNADPH Oxidase/antagonists & inhibitors/*metabolismNF-kappa B/metabolismNitric Oxide Synthase/drug effects/metabolismNitric Oxide Synthase Type IIPhosphoproteins/drug effects/metabolismProtein Kinase C/antagonists & inhibitors/*metabolismProtein Transport/drug effects/physiologyRatsRats, Sprague-DawleyReactive Oxygen Species/metabolismTumor Necrosis Factor-alpha/metabolism
DOI
10.1002/glia.20069
PMID
15390122
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
양, 명순주, 일로조, 은혜
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