title: Increased inducible nitric oxide synthase protein but limited nitric oxide formation occurs in astrocytes of the hph-1 (tetrahydrobiopterin deficient) mouse.
abstract: It has been suggested that decreased tetrahydrobiopterin (BH4) availability may be a useful tool for limiting excessive nitric oxide (NO) formation. In order to test this hypothesis we utilised cultured astrocytes derived from the brain of the hph-1 (BH4 deficient) mouse. In response to treatment with lipopolysaccharide and interferon-gamma (LPS/gammaIFN) levels of BH4 doubled in both wild type and hph-1 astrocytes. However, levels of BH4 in hph-1 astrocytes remained only 25% of the wild type astrocytes. Nitric oxide formation, measured with an NO-electrode, was 45% less from LPS/gammaIFN stimulated hph-1 astrocytes compared with wild type stimulated astrocytes. In contrast, iNOS specific activity and iNOS protein were enhanced in hph-1 stimulated astrocytes by 40 and 60%, respectively when compared with wild type. In conclusion it appears that whilst a decrease in BH4 may limit NO release per se, the possibility and consequences of long term 'over' induction of iNOS protein requires further consideration.
authors.affiliation: Department of Neurochemistry, Institute of Neurology, Queen Square, London WC1N 3BG, UK. barkerje@svhm.org.au
authors.forename: J E
authors.initials: JE
authors.lastname: Barker
authors.forename: H M
authors.initials: HM
authors.lastname: Strangward
authors.forename: M P
authors.initials: MP
authors.lastname: Brand
authors.forename: R D
authors.initials: RD
authors.lastname: Hurst
authors.forename: J M
authors.initials: JM
authors.lastname: Land
authors.forename: J B
authors.initials: JB
authors.lastname: Clark
authors.forename: S J
authors.initials: SJ
authors.lastname: Heales
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009994:Osmolar Concentration
chemical_list: D008070:Lipopolysaccharides; D001708:Biopterins; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C003402:sapropterin