RRC ID 72923
著者 Koshimura K, Murakami Y, Tanaka J, Kato Y.
タイトル Self-protection of PC12 cells by 6R-tetrahydrobiopterin from nitric oxide toxicity.
ジャーナル J Neurosci Res
Abstract Nitric oxide (NO) has cytotoxic effects but NO producing neurons are resistant to NO toxicity. These results suggest the presence of self-protecting factors for NO toxicity. Recently, 6R-tetrahydrobiopterin (6R-BH4), a cofactor for NO synthase (NOS), has been reported to degrade NO raising the possibility that 6R-BH4 acts as a self-protecting factor for NO toxicity. In PC12 cells which have NOS, three-day culture with sodium nitroprusside (SNP) or NOC-12, NO generators, at 10-100 microM increased nitrite and nitrate concentrations in the culture medium and induced death of PC12 cells. Coadministration of 6R-BH4 (10 or 30 microM) with SNP or NOC-12 prevented cell death with reduction of nitrite and nitrate in the medium. Inhibition of 6R-BH4 synthesis by 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor for GTP cyclohydrolase I, decreased cellular 6R-BH4 content and viable cell number. The inhibiting effects of DAHP were restored by exogenous 6R-BH4. NOS activity, as estimated by nitrite concentrations in the medium, was unchanged by DAHP. Hypoxanthine and xanthine oxidase, which produce superoxide, mimicked the cell-protecting effect of 6R-BH4 which is reported to generate superoxide during its autoxidation. These results suggest that 6R-BH4 acts as a self-protecting factor for NO toxicity with generation of superoxide in NO-producing neurons.
巻・号 54(5)
ページ 664-72
公開日 1998-12-1
DOI 10.1002/(SICI)1097-4547(19981201)54:5<664::AID-JNR11>3.0.CO;2-U
PII 10.1002/(SICI)1097-4547(19981201)54:5<664::AID-JNR11>3.0.CO;2-U
PMID 9843157
MeSH Animals Biopterin / analogs & derivatives* Biopterin / pharmacology GTP Cyclohydrolase / antagonists & inhibitors Hypoxanthine / pharmacology Neoplasm Proteins / metabolism Neuroprotective Agents / pharmacology* Nitrates / metabolism Nitric Oxide / toxicity* Nitric Oxide Donors / pharmacology Nitric Oxide Synthase / metabolism* Nitric Oxide Synthase Type I Nitrites / metabolism Nitroprusside / pharmacology Oxidation-Reduction PC12 Cells / drug effects* Rats Sugar Acids / pharmacology Superoxides / metabolism Xanthine Oxidase / pharmacology
IF 4.699
リソース情報
ヒト・動物細胞 PC-12(RCB0009)