Cardiovascular Research Institute, Yokohama City University School of Medicine, Fukuura, Kanazawa-Ku, Japan.
Curr Drug Metab. 2011 Jul;12(6):526-32. doi: 10.2174/138920011795713715.
Cytochrome P450 (CYP) represents a large family of enzymes that catalyze the oxidation of endogenous and exogenous compounds. The functions of CYP enzymes in the metabolism of xenobiotics have well been established in the liver. However, some CYP enzymes are highly expressed in the heart and catalyze arachidonic acid oxidation to a variety of eicosanoids, which attenuates ischemia-reperfusion injury of the heart. CYP-mediated cardioprotection is associated with activation of multiple pathways such as sarcolemmal and mitochondrial potassium channels, p42/p44 MAPK and PI3K-AKT signaling in cells. CYP enzymes also represent a significant source of reactive oxygen species (ROS) that may target cellular homeostatic mechanisms and mitochondria. CYP isoforms expressed in the heart are critical for generation of epoxyeicosatrienoic acids (EETs) and ROS. It has been demonstrated that CYP2J2 generates cardioprotective EETs, whereas another isozyme in the heart, CYP2C, generates EETs as well as detrimental ROS. Genetic polymorphisms of CYP2C or CYP2J2 have a pathologic impact on coronary artery diseases. Cardiac CYP enzymes can be involved in drug metabolism within the heart and influence pharmacologic efficacy. Metabolism mediated by CYP enzymes influences the survival of cardiomyocytes during ischemia, which is critical for treatment of human ischemic heart disease. In this review, we summarize current knowledge of this enzyme family and discuss the roles of CYP in ischemia-reperfusion injury of the heart.
细胞色素 P450（CYP）代表一个能够催化内源性和外源性化合物氧化的大型酶家族。CYP 酶在肝脏中外源物质代谢中的作用已经得到了很好的证实。然而，一些 CYP 酶在心脏中高度表达，并催化花生四烯酸氧化为多种类二十烷酸，从而减轻心脏的缺血再灌注损伤。CYP 介导的心脏保护作用与细胞中多种途径的激活有关，如肌浆网和线粒体钾通道、p42/p44 MAPK 和 PI3K-AKT 信号通路。CYP 酶也是活性氧（ROS）的重要来源，可能靶向细胞内稳态机制和线粒体。心脏中表达的 CYP 同工酶对于生成环氧二十碳三烯酸（EETs）和 ROS 至关重要。已经证明 CYP2J2 产生心脏保护的 EETs，而心脏中的另一种同工酶 CYP2C 则生成 EETs 和有害的 ROS。CYP2C 或 CYP2J2 的遗传多态性对冠状动脉疾病有病理影响。心脏 CYP 酶可以参与心脏内的药物代谢，并影响药物的疗效。CYP 酶介导的代谢影响心肌细胞在缺血期间的存活，这对治疗人类缺血性心脏病至关重要。在这篇综述中，我们总结了这个酶家族的现有知识，并讨论了 CYP 在心脏缺血再灌注损伤中的作用。
