Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues
Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues
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DOI：
10.1124/dmd.106.012823
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发表时间：
2007-04-01
影响因子：
3.9
通讯作者：
Goldstein, Joyce A.
中科院分区：
文献类型：
--
作者：
DeLozier, Tracy C.;Kissling, Grace E.;Goldstein, Joyce A.
细胞色素P450（P450）酶CYP2C8、CYP2C9和CYP2J2将花生四烯酸代谢为环氧二十碳三烯酸，已知其在调节血管张力和心血管稳态中至关重要。由于这些P450酶在心血管组织中的相对表达信息有限，因此本研究通过实时聚合酶链反应、免疫印迹和免疫组织化学检测了人心脏、主动脉和冠状动脉样本中CYP2C8、CYP2C9和CYP2J2 mRNA和蛋白的表达。CYP2J2和CYP2C9 mRNA水平在人心脏中高度可变，而CYP2C8 mRNA丰度较低。在人心脏中，CYP2J2 mRNA比CYP2C9或CYP2C8高约10（3）倍。然而，在一个缺血心脏中，CYP2C9 mRNA比CYP2J2或CYP2C8更丰富。在人主动脉中，平均CYP2C9 mRNA水平相似，比CYP2J2高50倍，比CYP2C8高5倍。在人冠状动脉中，CYP2C9 mRNA的平均值相似，比CYP2J2 mRNA高2倍，比CYP2C8 mRNA高6倍。免疫印迹结果显示，CYP2J2和CYP2C8蛋白在人类心脏中的水平相对较高，这通过免疫组织化学证实。免疫印迹法在一个缺血心脏中也检测到高水平的CYP2C9蛋白。在主动脉和冠状动脉中，CYP2C9的水平高于CYPJ2，而CYP2C8蛋白低于检测限。人体心脏中CYP 2J2和CYP 2C 8以及主动脉和冠状动脉中CYP 9和CYP 2J2的表达与这些酶在这些组织中的生理作用一致。
The cytochrome P450 ( P450) enzymes CYP2C8, CYP2C9, and CYP2J2 metabolize arachidonic acid to epoxyeicosatrienoic acids, which are known to be vital in regulation of vascular tone and cardiovascular homeostasis. Because there is limited information regarding the relative expression of these P450 enzymes in cardiovascular tissues, this study examined the expression of CYP2C8, CYP2C9, and CYP2J2 mRNA and protein in human heart, aorta, and coronary artery samples by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. CYP2J2 and CYP2C9 mRNA levels were highly variable in human hearts, whereas CYP2C8 mRNA was present in lower abundance. CYP2J2 mRNA was approximately 10(3) times higher than CYP2C9 or CYP2C8 in human heart. However, CYP2C9 mRNA was more abundant than CYP2J2 or CYP2C8 in one ischemic heart. In human aorta, mean CYP2C9 mRNA levels were similar to 50 times higher than that of CYP2J2 and 5-fold higher than that of CYP2C8. In human coronary artery, mean values for CYP2C9 mRNA were similar to 2-fold higher than that of CYP2J2 mRNA and 6-fold higher than that of CYP2C8 mRNA. Immunoblotting results show relatively high levels of CYP2J2 and CYP2C8 protein in human hearts, which was confirmed by immunohistochemistry. CYP2C9 protein was also detected at high levels in one ischemic heart by immunoblotting. CYP2C9 was present at higher levels than CYPJ2 in aorta and coronary artery, whereas CYP2C8 protein was below the limits of detection. The expression of CYP2J2 and CYP2C8 in human heart, and CYPC9 and CYP2J2 in aorta and coronary artery is consistent with a physiological role for these enzymes in these tissues.