Differential effects of soluble epoxide hydrolase inhibition and CYP2J2 overexpression on postischemic cardiac function in aged mice.
Differential effects of soluble epoxide hydrolase inhibition and CYP2J2 overexpression on postischemic cardiac function in aged mice.
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DOI：
10.1016/j.prostaglandins.2012.08.001
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发表时间：
2013-07
影响因子：
2.9
通讯作者：
Seubert JM
中科院分区：
文献类型：
--
作者：
Chaudhary KR;Zordoky BN;Edin ML;Alsaleh N;El-Kadi AO;Zeldin DC;Seubert JM
细胞色素p450（CYP）表氧化酶，即CYP 2C和CYP 2 J亚家族酶，在脂肪酸代谢中起重要作用[1]。在心脏中，CYP 2 J含量丰富，主要参与由花生四烯酸生物合成环氧二十碳三烯酸（5，6-、8，9-、11，12-和14，15-雌二醇）[2]。雌二醇在细胞信号传导中发挥重要作用，并在心血管系统中具有多种生物活性，包括血管舒张、抗炎、抗纤维化、利钠和抗凋亡作用[3，4]。EET水平的调节可以通过重新掺入磷脂膜或通过β-氧化为较小的反应性环氧化物[4-6]发生;然而，主要途径是通过环氧化物水解酶代谢为无活性的邻位二醇[4，6，7]。在哺乳动物组织中发现了两种主要的环氧化物水解酶，微粒体环氧化物水解酶（mEH）和可溶性环氧化物水解酶（sEH或Ephx 2）[8]。越来越多的证据表明，Ephx在缺血再灌注（I/R）损伤中具有重要的功能作用[9-13]。我们小组和其他人的研究已经证明了Escherichia coli的心脏保护作用[1，13-15]。研究报告，Ephx 2基因靶向缺失的小鼠（sEH敲除，sEH无效）具有增强的左心室功能缺血后恢复，这是由PI 3 K通路和K+通道的激活介导的[10，14]。使用药理学抑制剂（sEHis）抑制sEH也可保护心脏免受I/R损伤[12，13]。CYP 2 J2 Tr小鼠中CYP 2 J2的心肌细胞特异性过表达导致缺血后功能恢复改善和梗死面积减小[9，16]。此外，也已证明用外源性雌二醇治疗对I/R损伤具有保护作用[1，17]。根据目前的知识，Ekaline的心脏保护机制表明涉及信号传导途径，包括磷酸肌醇3-激酶（PI 3 K）-Akt、心脏激素分泌增加和心脏离子通道（如ATP敏感性K+通道和BKCa通道）的激活[1，9，10，14，17]。
Cytochrome p450 (CYP) epoxygenases, CYP2C and CYP2J subfamilies enzymes, play important role in fatty acid metabolism [1]. In the heart, CYP2J is abundant and predominantly involved in the biosynthesis of epocyeicosatrienoic acids (5, 6-, 8, 9-, 11, 12-, and 14, 15-EETs) from arachidonic acid [2]. EETs play important role in cellular signaling and possess numerous biological activities in the cardiovascular system including vasodilatory, anti-inflammatory, anti-fibrotic, natriuretic and anti-apoptotic effects [3, 4]. Modulation of EET-levels can occur via reincorporation into phospholipid membranes or by β-oxidation to smaller reactive epoxides [4–6]; however, the predominant pathway occurs through metabolism to inactive vicinal diols by epoxide hydrolases [4, 6, 7]. Two major epoxide hydrolases are found in mammalian tissues, microsomal epoxide hydrolase (mEH) and soluble epoxide hydrolase (sEH or Ephx2)[8].Accumulating evidence indicates that EETs have important functional roles in ischemia reperfusion (I/R) injury [9–13]. Studies from our group and others have demonstrated cardioprotective effects of EETs [1, 13–15]. Studies reported that mice with the targeted deletion of the Ephx2 gene (sEH knockout, sEH null) had enhanced postischemic recovery of left ventricular function, which was mediated by activation of the PI3K pathway and K+ channels [10, 14]. Inhibition of sEH, using pharmacological inhibitors (sEHis) also protects the heart against I/R injury [12, 13]. Cardiomyocyte specific over-expression of CYP2J2 in CYP2J2 Tr mice leads to improved functional recovery and reduced infarct size after ischemia [9, 16]. Moreover, treatment with exogenous EETs has also been demonstrated to be protective against I/R injury [1, 17]. According to current knowledge, the cardioprotective mechanism (s) of EETs suggest involvement of signaling pathways including phosphoinositide 3-kinase (PI3K)–Akt, increased secretion of cardiac hormones, and activation of cardiac ion channels such as ATP-sensitive K+ channels and BKCa channels [1, 9, 10, 14, 17].
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DOI：
10.1016/0735-1097(96)00070-8
发表时间：
1996-06-01
影响因子：
24
作者：
Abete, P;Ferrara, N;Rengo, F
通讯作者：
Rengo, F
DOI：
10.3724/sp.j.1263.2011.00159
发表时间：
2011-09
期刊：
Journal of geriatric cardiology : JGC
影响因子：
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作者：
Chaudhary KR;El-Sikhry H;Seubert JM
通讯作者：
Seubert JM
影响因子：
82.9
作者：
Moghaddam, MF;Grant, DF;Hammock, BD
通讯作者：
Hammock, BD
DOI：
10.1152/ajpheart.00448.2002
发表时间：
2002-12-01
影响因子：
4.8
作者：
Fang, X;Weintraub, NL;Spector, AA
通讯作者：
Spector, AA
DOI：
10.1124/jpet.111.180505
发表时间：
2011-11-01
影响因子：
3.5
作者：
Liu, Liu;Chen, Chen;Wang, Dao Wen
通讯作者：
Wang, Dao Wen