title: Coinduction of inducible nitric oxide synthase and arginine recycling enzymes in cytokine-stimulated PC12 cells and high output production of nitric oxide.
abstract: Nitric oxide (NO) is involved in many physiological and pathological processes in the brain. NO is synthesized from arginine by nitric oxide synthase (NOS), and the citrulline generated as a by-product can be recycled to arginine by argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) via the citrulline-NO cycle. When neuronal PC12 cells differentiated with nerve growth factor were treated with interferon-gamma (IFNgamma) and tumor necrosis factor-alpha (TNFalpha), iNOS and AS mRNAs and proteins were markedly induced, with AL mRNA and protein being weakly induced. Cationic amino acid transporter-1 and -2 were not induced. IFNgamma or TNFalpha alone was ineffective. A large amount of NO (190 microM NO(2)(-) plus NO(3)(-) in culture medium in 24 h) was produced from arginine by cytokine-stimulated cells, and arginine could be replaced by citrulline. iNOS induction and NO production were attenuated by dexamethasone and dibutyryl cAMP and even more strongly so when combined. Therefore, a large amount of NO is produced in cytokine-stimulated PC12 cells following to induction of iNOS and citrulline-arginine recycling is important for NO production.
authors.affiliation: Department of Molecular Genetics, Kumamoto University School of Medicine, Honjo 2-2-1, 860-0811, Kumamoto, Japan.
authors.forename: W Y
authors.initials: WY
authors.lastname: Zhang
authors.forename: T
authors.initials: T
authors.lastname: Gotoh
authors.forename: S
authors.initials: S
authors.lastname: Oyadomari
authors.forename: M
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism*; D001123:Argininosuccinate Lyase / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002956:Citrulline / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D009569:Nitric Oxide; D003994:Bucladesine; D003907:Dexamethasone; D007371:Interferon-gamma; D020932:Nerve Growth Factor; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001123:Argininosuccinate Lyase; D001124:Argininosuccinate Synthase