Cytochrome P450 is responsible for nitric oxide generation from NO-aspirin and other organic nitrates.
Cytochrome P450 is responsible for nitric oxide generation from NO-aspirin and other organic nitrates.
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DOI：
10.2133/dmpk.22.15
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发表时间：
2007
影响因子：
2.1
通讯作者：
Y. Minamiyama;S. Takemura;S. Imaoka;Y. Funae;S. Okada
中科院分区：
文献类型：
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作者：
Y. Minamiyama;S. Takemura;S. Imaoka;Y. Funae;S. Okada
一氧化氮(NO)从非阿司匹林(NCX-4016)的生物转化尚不清楚。我们以前报道过细胞色素P450(P450)在硝酸甘油(NTG)和硝酸异山梨酯(ISDN)等其他有机硝酸盐生成NO的过程中起重要作用。本研究利用转染人P450基因的淋巴母细胞微粒体或酵母表达的纯化的P450亚型，研究了人细胞色素P450亚型在NCX-4016细胞生成NO中的作用。在其他异构体中，细胞色素P1A2和细胞色素P450 2J2与NCX-4016产生的NO密切相关。事实上，这些异构体在人类冠状动脉内皮细胞中也被检测到。这些结果表明，NADPH-细胞色素P450还原酶和P450系统参与了NCX-4016以及其他有机硝酸盐生成NO的过程。
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.