RRC ID 39814
Author Mori H, Arai T, Hirota K, Ishii H, Endo N, Makino K, Fukuda K.
Title Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger, on production of nitric oxide in RAW 264.7 macrophages.
Journal Biochim Biophys Acta
Abstract As well as superoxide generated from neutrophils, nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in macrophages plays an important role in inflammation. We previously showed that 6-formylpterin, a xanthine oxidase inhibitor, has a superoxide scavenging activity. In the present study, to elucidate other pharmacological activities of 6-formylpterin, we investigated the effects of 6-formylpterin on production of nitric oxide (NO) in the murine macrophage cell line RAW 264.7 stimulated by lipopolysaccharide (LPS) and interferon-gamma (INF-gamma). 6-Formylpterin suppressed the expression of iNOS, and it also inhibited the catalytic activity of iNOS, which collectively resulted in the inhibition of NO production in the stimulated macrophages. However, 6-formylpterin did not scavenge the released NO from an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). These results indicate that 6-formylpterin inhibits pathological NO generation from macrophages during inflammation, but that it does not disturb the physiological action of NO released from other sources.
Volume 1474(1)
Pages 93-9
Published 2000-3-6
DOI 10.1016/s0304-4165(99)00210-x
PII S0304-4165(99)00210-X
PMID 10699495
MeSH Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology Cell Line Cell Survival / drug effects Cyclooxygenase 2 Electron Spin Resonance Spectroscopy Free Radical Scavengers / pharmacology Interferon-gamma Isoenzymes / genetics Isoenzymes / metabolism Lipopolysaccharides Luciferases Macrophages / drug effects* Macrophages / metabolism Mice Molecular Structure Nitric Oxide / biosynthesis* Nitric Oxide Synthase / genetics Nitric Oxide Synthase / metabolism Nitric Oxide Synthase Type II Prostaglandin-Endoperoxide Synthases / genetics Prostaglandin-Endoperoxide Synthases / metabolism Pteridines / chemical synthesis Pteridines / pharmacology* Pterins* RNA, Messenger / metabolism Spin Trapping Superoxides / metabolism* Xanthine Oxidase / antagonists & inhibitors
IF 3.411
Times Cited 8
WOS Category BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Human and Animal Cells RAW 264(RCB0535)