title: Role of MAPK/ERK1/2 in the glucose deprivation-induced death in immunostimulated astroglia.
abstract: Recently we have reported that glucose deprivation induces the potentiated death and loss of ATP in immunostimulated astroglia via the production of NO and eventually peroxynitrite. This study examined the role of the ERK1/2 signaling pathways in the glucose deprivation-induced death of immunostimulated astroglia. Immunostimulation with LPS+IFN-gamma induced the sustained activation of ERK1/2 for up to 48 h. Glucose deprivation caused the loss of ATP and consequently cell death in immunostimulated astroglia, which was significantly blocked by the treatment with the ERK kinase (MEK1) inhibitor, PD98059 (10-40 microM), to inhibit the ERK1/2 pathways. The systems for generating NO (iNOS) or superoxide (NADPH oxidase) were regulated by the ERK1/2 signaling pathways because the addition of PD98059 reduced the level of both. Interestingly, glucose deprivation caused an approximately two-fold increase in the level of peroxynitrite formation in immunostimulated astroglia, which was significantly reduced by the PD98059 treatment. This demonstrates that the ERK1/2 signaling pathways play an important role in glucose deprivation-induced death in immunostimulated astroglia by regulating the generation of NO, superoxide and their reaction product, peroxynitrite.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Yoo
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Byoung Hee
authors.initials: BH
authors.lastname: Han
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002545:Brain Ischemia / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005911:Gliosis / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency / Q000378:metabolism*; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D019255:NADPH Oxidases / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000276:immunology; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D030421:Peroxynitrous Acid; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D005947:Glucose