title: Cytochrome P450 is responsible for nitric oxide generation from NO-aspirin and other organic nitrates.
abstract: Nitric oxide (NO) biotransformation from NO-aspirin (NCX-4016) is not clearly understood. We have previously reported that cytochrome P450 (P450) plays important role in NO generation from other organic nitrates such as nitroglycerin (NTG) and isosorbide dinitrate (ISDN). The present study was designed to elucidate the role of human cytochrome P450 isoforms in NO formation from NCX-4016, using lymphoblast microsomes transfected with cDNA of human P450 or yeast-expressed, purified P450 isoforms. CYP1A2 and CYP2J2, among other isoforms, were strongly related to NO production from NCX-4016. In fact, these isoforms were detected in human coronary endothelial cells. These results suggest that NADPH-cytochrome P450 reductase and the P450 system participate in NO formation from NCX-4016, as well as other organic nitrates.
authors.affiliation: Department of Anti-aging Food Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan. yukiko@med.osaka-cu.ac.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.forename: Susumu
authors.initials: S
authors.lastname: Imaoka
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Funae
authors.forename: Shigeru
authors.initials: S
authors.lastname: Okada
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000378:metabolism; D003331:Coronary Vessels / Q000201:enzymology / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007548:Isosorbide Dinitrate / Q000378:metabolism; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology
chemical_list: D018076:DNA, Complementary; D007527:Isoenzymes; C488176:N-acetyl-S-(alpha-methyl-4-(2-methylpropyl)benzeneacetyl)cysteine 4-(nitrooxy)butyl ester; D009566:Nitrates; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D007548:Isosorbide Dinitrate; D001241:Aspirin