Isoforms of cytochrome P450 on organic nitrate‐derived nitric oxide release in human heart vessels

FEBS Letters

Minamiyama, Yukiko³  Inoue, Masayasu⁴  Okada, Shigeru³  Funae, Yoshihiko²  Akiyama, Takashi³  Takemura, Shigekazu¹  Imaoka, Susumu² 

[1] Department of Surgery, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan;Department of Biological Chemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan;Department of Pathology, Faculty of Medicine, Okayama University, Shikatacho, Okayama 700-8558, Japan;Department of Biochemistry, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan

关键词: Organic nitrate;    Nitric oxide;    Cytochrome P450;    Human heart vessel;    CYP3A4;    P450;    cytochrome P450;    G6P;    glucose-6 phosphate;    G6PDH;    glucose-6 phosphate dehydrogenase;    GTN;    glyceryl trinitrate;    GST;    glutathione S-transferase;    IgG;    immunoglobulin G;    ISDN;    isosorbide dinitrate;    NO;    nitric oxide;    NO2 −;    nitrite;   

DOI  :  10.1016/S0014-5793(99)00612-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Glutathione S-transferases and the cytochrome P450 system have been proposed for the vascular biotransformation systems in the metabolic activation of organic nitrates. The present study was designed to elucidate the role of human cytochrome P450 isoforms on nitric oxide formation from organic nitrates using lymphoblast microsomes transfected with human CYP isoforms cDNA. CYP3A4-transfected microsomes had the most effective potential of nitric oxide formation from isosorbide dinitrate. Anti-CYP3A2 antibody (which cross-reacts with CYP3A4) or ketoconazole (an inhibitor of the CYP3A superfamily) inhibited nitric oxide formation from isosorbide dinitrate in rat heart microsomes. Immunohistochemistry of human heart also showed intense bindings of CYP3A4 antibody in the endothelium of the endocardium and coronary vessels. These results suggest that the CYP3A4-NADPH-cytochrome P450 reductase system specifically participates in nitric oxide formation from isosorbide dinitrate.

【 授权许可】

Unknown