Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.17.3.2 (
xanthine oxidase
)
8,383
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Self-protection of PC12 cells by 6R-tetrahydrobiopterin from nitric oxide toxicity. 984 57
