Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated receptors in the rat kidney
Regulation of cytochrome P-450 4A activity by peroxisome proliferator-activated receptors in the rat kidney
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DOI：
10.1291/hypres.26.929
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发表时间：
2003-11-01
影响因子：
5.4
通讯作者：
Ito, S
中科院分区：
文献类型：
--
作者：
Ishizuka, T;Ito, O;Ito, S
在大鼠肾脏中测定细胞色素P-450 4A、过氧化物酶体增殖物激活受体（PPAR）α和PPARgamma蛋白的定位以及PPAR激动剂对P-450 4A表达和活性的诱导。通过免疫印迹分析评价这些蛋白在分离的肾单位片段中的表达，并测量20-羟基二十碳四烯酸（20-HETE）的产生作为P-450 4A活性。P-450 4A蛋白主要表达于近端小管（PT），在肾小球前小动脉（Art）、肾小球（Glm）和髓质粗升支（mTAL）中表达较低，但在内髓集合管（IMCD）中未检测到其表达。PPARalpha蛋白在PT和mTAL中表达，PPARgamma蛋白在IMCD和mTAL中表达。用PPARalpha激动剂氯贝特治疗，增加了从肾皮质制备的微粒体中P-450 4A蛋白水平和20-HETE的产生，而用PPARgamma激动剂吡格列酮治疗，对两者都没有影响。这些结果表明，PPARalpha和PPARgamma蛋白定位于不同的肾单位节段，并且通过PPAR激动剂诱导P-450 4A表达和活性与相应的PPAR同种型的肾单位特异性定位相关。
The localization of cytochrome P-450 4A, peroxisome proliferator-activated receptor (PPAR) alpha, and PPARgamma proteins, and the inducibility of P-450 4A expression and activity by PPAR agonists were determined in the rat kidney. The expressions of these proteins in isolated nephron segments were evaluated by immunoblot analysis, and the production of 20-hydroxyeicosatetraenoic acid (20-HETE) was measured as P-450 4A activity. P-450 4A proteins were expressed predominantly in the proximal tubule (PT), with lower expression in the preglomerular arteriole (Art), glomerulus (Glm), and medullary thick ascending limb (mTAL), but their expression was not detected in the inner medullary collecting duct (IMCD). PPARalpha protein was expressed in the PT and mTAL, and PPARgamma protein was expressed in the IMCD and mTAL. Treatment with clofibrate, the PPARalpha agonist, increased P-450 4A protein levels and the production of 20-HETE in microsomes prepared from the renal cortex, whereas treatment with pioglitazone, the PPARgamma agonist, affected neither of them. These results indicate that PPARalpha and PPARgamma proteins are localized in different nephron segments and the inducibility of P-450 4A expression and activity by the PPAR agonists correlates with the nephron-specific localization of the respective PPAR isoforms.