The roles of cytochrome p450 in ischemic heart disease.
The roles of cytochrome p450 in ischemic heart disease.
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DOI：
10.2174/138920011795713715
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发表时间：
2011-06
影响因子：
2.3
通讯作者：
Motohiko Sato;U. Yokoyama;T. Fujita;S. Okumura;Yoshihioro Ishikawa
中科院分区：
文献类型：
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作者：
Motohiko Sato;U. Yokoyama;T. Fujita;S. Okumura;Yoshihioro Ishikawa
细胞色素P450 （CYP）代表了一个催化内源性和外源性化合物氧化的大家族酶。在肝脏中，CYP酶在异种生物代谢中的作用已经得到了很好的证实。然而，一些CYP酶在心脏中高表达，并催化花生四烯酸氧化成多种类二十烷，从而减轻心脏缺血再灌注损伤。cypp介导的心脏保护与细胞中多种途径的激活有关，如肌层和线粒体钾通道、p42/p44 MAPK和PI3K-AKT信号。CYP酶也是活性氧（ROS）的重要来源，它可能针对细胞稳态机制和线粒体。在心脏中表达的CYP异构体对于环氧二碳三烯酸（EETs）和ROS的生成至关重要。已经证明CYP2J2产生保护心脏的eet，而心脏中的另一种同工酶CYP2C产生eet以及有害的ROS。CYP2C或CYP2J2基因多态性对冠状动脉疾病有病理影响。心脏CYP酶参与药物在心脏内的代谢，影响药物的药理作用。CYP酶介导的代谢影响心肌细胞在缺血时的存活，对人类缺血性心脏病的治疗至关重要。在这篇综述中，我们总结了目前对该酶家族的认识，并讨论了CYP在心脏缺血再灌注损伤中的作用。
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.