title: MeCP2 deficiency enhances glutamate release through NF-κB signaling in myeloid derived cells.
abstract: The signaling pathway involved in regulating glutamate release was investigated. Glutaminase mRNA levels were higher in microglia isolated from mice treated with lipopolysaccharide. Pam3CSK and lipopolysaccharide stimulated glutamate release in neonatal mouse microglia cultures, which was attenuated by NF-κB inhibitors. Higher levels of glutaminase mRNA and glutamate release were observed in human peripheral blood mononuclear cells made MeCP2 deficient with MeCP2 shRNA, which was blocked by NF-κB inhibitors. NF-κB inhibitors also decreased the higher levels of glutaminase mRNA in MeCP2 deficient THP1 monocyte cell lines. Finally, an inverse relation was observed between MeCP2 levels and NF-κB reporter activity in THP1 cells. We suggest that NF-κB pathway is involved in the release of glutamate in MeCP2 deficient cells from the myeloid lineage.
authors.affiliation: Hugo Moser Institute at the Kennedy Krieger, USA; Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, USA.
authors.forename: Cliona M
authors.initials: CM
authors.lastname: O'Driscoll
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Bressler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism*; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency*; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D051783:Methyl-CpG-Binding Protein 2; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D018698:Glutamic Acid; D001616:beta-Galactosidase; D005972:Glutaminase
keywords: Glutamate; MeCP2; Microglia; NF-κB; Peripheral blood mononuclear cells