Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney.
Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney.
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发表时间：
2000-05
影响因子：
3.6
通讯作者：
Zhigang Yu;Linn M. Huse;P. Adler;L. Graham;Jixiang Ma;D. Zeldin;D. Kroetz
中科院分区：
文献类型：
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作者：
Zhigang Yu;Linn M. Huse;P. Adler;L. Graham;Jixiang Ma;D. Zeldin;D. Kroetz
环氧二十碳三烯酸(EETs)是细胞色素P450(CYP)催化花生四烯酸在肾脏代谢的主要产物。EETs对肾血管张力、肾小管离子和水运输的有效作用暗示了它们在调节肾功能和血压中的作用。本研究旨在验证自发性高血压大鼠(SHR)肾脏中CYP催化的EET形成发生改变的假说。在花生四烯酸与自发性高血压大鼠(SHR)肾皮质微体孵育时，14，15-和11，12-EET的形成比正常血压的Wistar-京都(WKY)大鼠的微体高约2倍。这与自发性高血压大鼠皮质和外髓中CYP2J2免疫反应蛋白的表达增加一致。而在SHR和WKY肾脏中，细胞色素P450 E和环氧合酶C的表达水平无显著差异。蛋白质和RNA分析表明，在SHR肾脏中过度表达的CYP2J2免疫活性蛋白与已知的大鼠CYP2J亚型不同。通过测量尿液中的EET排泄量，体内也记录了EET的形成。重要的是，14，15-和11，12-EET在SHR的排泄率分别是WKY肾脏的2.5和1.8倍。这些研究在体外和体内都为SHR肾脏中EET的形成增加提供了证据，并发现了一种在高血压肾脏中差异表达的新的CYP2J2免疫反应蛋白。根据已知的EETs的生物学特性，这些发现可能对阐明自发性高血压大鼠肾血管张力和肾小管离子转运的机制有重要意义。
Epoxyeicosatrienoic acids (EETs) are major products of cytochrome P450 (CYP)-catalyzed metabolism of arachidonic acid in the kidney. The potent effect of EETs on renal vascular tone and tubular ion and water transport implicates their role in the regulation of renal function and blood pressure. The present study was designed to test the hypothesis that CYP-catalyzed EET formation was altered in the spontaneously hypertensive rat (SHR) kidney. The formation of 14,15- and 11,12-EET was approximately 2-fold higher in incubations of arachidonic acid with SHR renal cortical microsomes relative to microsomes from normotensive Wistar-Kyoto (WKY) rats. This was consistent with increased expression of a CYP2J2 immunoreactive protein in the SHR cortex and outer medulla. In contrast, there was no significant difference in the levels of the CYP2E and CYP2C epoxygenases in SHR and WKY kidneys. Protein and RNA analysis suggests that the CYP2J2 immunoreactive protein that is overexpressed in the SHR kidney is distinct from the known rat CYP2J isoforms. EET formation also was documented in vivo from measurements of urinary EET excretion. Importantly, the excretion rates of 14,15-, and 11,12-EETs were 2.5- and 1.8-fold higher, respectively, in SHR than WKY kidney. These studies provide both in vitro and in vivo evidence for increased EET formation in the SHR kidney and identify a novel CYP2J2 immunoreactive protein that is differentially expressed in the hypertensive kidney. In light of the known biological properties of the EETs, these findings may be important in elucidating the mechanisms that control renal vascular tone and tubular ion transport in the SHR.