State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
Drug Metab Rev. 2013 Aug;45(3):311-52. doi: 10.3109/03602532.2013.806537.
Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular systems and lower levels in the intestine, kidney, lung, pancreas, brain, liver, etc. During the past 15 years, CYP2J2 has attracted much attention for its epoxygenase activity in arachidonic acid (AA) metabolism. It converts AA to four epoxyeicosatrienoic acids (EETs) that have various biological effects, especially in the cardiovascular systems. In recent publications, CYP2J2 is shown highly expressed in various human tumor cells, and its EET metabolites are demonstrated to implicate in the pathologic development of human cancers. CYP2J2 is also a human CYP that involved in phase I xenobiotics metabolism. Antihistamine drugs and many other compounds were identified as the substrates of CYP2J2, and studies have demonstrated that these substrates have a broad structural diversity. CYP2J2 is found not readily induced by known P450 inducers; however, its expression could be regulated in some pathological conditions, might through the activator protein-1(AP-1), the AP-1-like element and microRNA let-7b. Several genetic mutations in the CYP2J2 gene have been identified in humans, and some of them have been shown to have potential associations with some diseases. With the increasing awareness of its roles in cancer disease and drug metabolism, studies about CYP2J2 are still going on, and various inhibitors of CYP2J2 have been determined. Further studies are needed to delineate the roles of CYP2J2 in disease pathology, drug development and clinical practice.
细胞色素 P450 2J2（CYP2J2）主要存在于人类肝外组织中，在心脑血管系统中表达丰富，在肠道、肾脏、肺、胰腺、大脑、肝脏等组织中表达水平较低。在过去的 15 年中，CYP2J2 因其在花生四烯酸（AA）代谢中的环氧合酶活性而备受关注。它将 AA 转化为四种环氧二十碳三烯酸（EETs），具有多种生物学效应，特别是在心脑血管系统中。在最近的出版物中，CYP2J2 被证明在各种人类肿瘤细胞中高度表达，其 EET 代谢物被证明与人类癌症的病理发展有关。CYP2J2 也是参与 I 相外源性物质代谢的人类 CYP。抗组胺药物和许多其他化合物被鉴定为 CYP2J2 的底物，研究表明这些底物具有广泛的结构多样性。CYP2J2 不易被已知的 P450 诱导剂诱导，但在某些病理条件下其表达可以受到调节，可能通过激活蛋白-1（AP-1）、AP-1 样元件和 microRNA let-7b。在人类中已经鉴定出 CYP2J2 基因的几个遗传突变，其中一些已经显示出与某些疾病有潜在的关联。随着人们对其在癌症疾病和药物代谢中的作用的认识不断提高，对 CYP2J2 的研究仍在继续，并确定了几种 CYP2J2 的抑制剂。需要进一步的研究来阐明 CYP2J2 在疾病病理学、药物开发和临床实践中的作用。
