Decreased expression of catechol-O-methyltransferase in the renal cortex of malignant spontaneously hypertensive rats.
Decreased expression of catechol-O-methyltransferase in the renal cortex of malignant spontaneously hypertensive rats.
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恶性自发性高血压大鼠肾皮质儿茶酚-O-甲基转移酶表达降低。
DOI：
--
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发表时间：
2009
影响因子：
2.2
通讯作者：
H. Munakata
中科院分区：
文献类型：
--
作者：
K. Ooshima;Shingen Ozaki;M. Tabuchi;H. Higashino;E. Honda;A. Park;S. Arima;H. Munakata
原发性高血压是一种发病机制不明的疾病，尽管肾功能是其病因的重要因素。易卒中的自发性高血压（SHRSP）大鼠提供了原发性高血压的动物模型。为了了解高血压的原因，识别高血压大鼠和血压正常大鼠之间差异表达的蛋白质可能提供一个关键。在这里，蛋白质在肾皮质从SHRSP大鼠，恶性卒中倾向的自发性高血压（M-SHRSP）大鼠，和Wistar京都（WKY）大鼠作为正常血压对照进行了二维差异凝胶电泳（2D-DIGE）。胰蛋白酶凝胶内消化后，通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOFMS）鉴定蛋白质。几种蛋白质在高血压大鼠和正常血压大鼠之间表现出不同的表达模式。其中，我们专注于儿茶酚-O-甲基转移酶（COMT），因为这种酶使儿茶酚胺失活，可能影响血压。为了证实COMT在每只动物中的差异表达，我们进行了Western blot分析，结果显示，COMT在M-SHRSP大鼠中的表达低于对照组和SHRSP大鼠，表明血压和COMT的表达相关。事实上，在10周龄时，M-SHRSP大鼠的血压显著高于SHRSP大鼠。免疫组织化学和免疫荧光研究表明，COMT在肾皮质定位于肾小管上皮细胞。COMT在M-SHRSP大鼠肾皮质肾小管上皮细胞的表达低于正常血压大鼠。提示COMT表达降低可能是导致高血压发生发展的重要因素。
Essential hypertension is a disease of unknown pathogenesis, although renal function has been implicated as an important factor in its cause. Stroke-prone spontaneously hypertensive (SHRSP) rats provide an animal model of essential hypertension. To understand the cause of hypertension, identifying proteins that are differentially expressed between hypertensive and normotensive rats may provide a key. Here, proteins in the renal cortex from SHRSP rats, malignant stroke-prone spontaneously hypertensive (M-SHRSP) rats, and Wistar Kyoto (WKY) rats as a normotensive control were subjected to two-dimensional difference gel electrophoresis (2D-DIGE). After in-gel digestion by trypsin, proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Several proteins showed differential expression patterns between hypertensive and normotensive rats. Among them, we focused on catechol-O-methyltransferase (COMT) because this enzyme inactivates catecholamines, possibly affecting blood pressure. To confirm the differential expression of COMT in each animal, we conducted Western blot analysis, which revealed that the expression of COMT is lower in M-SHRSP rats than in control and SHRSP rats, indicating that blood pressure and expression of COMT are related. In fact, the blood pressure of M-SHRSP rats was significantly higher than that of SHRSP rats at age of 10 weeks. Immunohistochemical and immunofluorescence studies showed that COMT in renal cortex is localized in tubular epithelial cells. The expression of COMT is lower in the renal cortex tubular epithelium of M-SHRSP rats than in normotensive rats. These results suggest that the decreased expression of COMT may be an important factor leading to the development of hypertension.
五个大家族儿茶酚-O-甲基转移酶活性遗传的主要基因模型。
DOI：
10.1002/ajmg.1320190214
发表时间：
1984
期刊：
American journal of medical genetics
影响因子：
--
作者：
Siervogel,RM;Weinshilboum,R;Wilson,AF;Elston,RC
通讯作者：
Elston,RC