title: Glucose deprivation decreases nitric oxide production via NADPH depletion in immunostimulated rat primary astrocytes.
abstract: We have previously reported that the production of nitric oxide (NO) in immunostimulated astrocytes was markedly decreased under glucose-deprived conditions. The present study was undertaken to find the contributing factor(s) for the decreased NO production in glucose-deprived immunostimulated astrocytes. NO production in rat primary astrocytes was stimulated for 24-48 h by cotreatment with lipopolysaccharides (1 microg/ml) and interferon-gamma (100 U/ml). Decreased NO production in immunostimulated astrocytes by glucose deprivation was mimicked by the glycolytic inhibitor 2-deoxyglucose and reversed by addition of pyruvate and lactate. Glucose deprivation did not alter the expression of inducible nitric oxide synthase (iNOS) in immunostimulated astrocytes. Addition of beta-NADPH, but not tetrahydrobiopterine, both of which are essential cofactors for NOS function, completely restored the NO production that was decreased in glucose-deprived immunostimulated astrocytes. Glucose deprivation and immunostimulation synergistically reduced intracellular NADPH level in astrocytes. The results indicate that glucose deprivation decreases NO production in immunostimulated astrocytes by depleting intracellular NADPH, a cofactor of iNOS.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Seoul National University, Seoul, South Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Choi
authors.forename: Jae Ryun
authors.initials: JR
authors.lastname: Ryu
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
authors.forename: Jung-Jin
authors.initials: JJ
authors.lastname: Choi
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Hee-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
authors.forename: Sun Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Hyoung Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Kim
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D003847:Deoxyglucose / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D005947:Glucose / Q000172:deficiency*; D005978:Glutathione / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009249:NADP / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism*; D019289:Pyruvic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D001708:Biopterins; D009569:Nitric Oxide; D019344:Lactic Acid; D009249:NADP; D007371:Interferon-gamma; D019289:Pyruvic Acid; D003847:Deoxyglucose; D019001:Nitric Oxide Synthase; C003402:sapropterin; D005978:Glutathione; D005947:Glucose