Modulation of cardiac contractility by serine/threonine protein phosphatase type 5
Modulation of cardiac contractility by serine/threonine protein phosphatase type 5
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DOI：
10.1016/j.ijcard.2010.09.009
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发表时间：
2012-01-26
影响因子：
3.5
通讯作者：
Neumann, Joachim
中科院分区：
文献类型：
--
作者：
Gergs, Ulrich;Boknik, Peter;Neumann, Joachim
背景资料：蛋白磷酸酶5（PP 5）是一种丝氨酸/苏氨酸磷酸酶，广泛表达于包括心脏在内的哺乳动物组织中，但其在心脏中的生理作用尚不清楚。因此，我们使用转基因小鼠模型，以获得第一次洞察的心脏作用的PP 5。方法和结果：我们建立了转基因小鼠与心肌细胞特异性过表达PP 5。PP 5的成功过表达证明了蛋白质印迹，免疫组化和增强花生四烯酸刺激的蛋白磷酸酶活性在转基因心脏。在离体心肌细胞、离体器官和完整动物的水平上检查心脏功能。而钙瞬变和细胞缩短保持不变，L-型钙电流减少从转基因小鼠分离的心肌细胞。在基础条件下和β-肾上腺素能刺激后，离体灌注心脏的心室收缩力降低。在完整的动物，超声心动图显示左心室直径增加，收缩力和侵入性测量的血液动力学性能左心室导管插入术表现出降低响应β-肾上腺素能刺激的转基因小鼠相比，野生型。结论：PP 5的过度表达影响的收缩力和β-肾上腺素能信号在转基因小鼠的心脏。总之，这些发现表明PP 5在心脏功能中的调节作用。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Background: Protein phosphatase 5 (PP5) a serine/threonine phosphatase is ubiquitously expressed in mammalian tissues including the heart, but its physiological role in the heart is still unknown. Therefore, we used a transgenic mouse model to get a first insight into the cardiac role of PP5.Methods and results: We generated transgenic mice with cardiac myocyte specific overexpression of PP5. Successful overexpression of PP5 was demonstrated by Western blotting, immunohistochemistry and enhanced arachidonic acid-stimulated protein phosphatase activity in transgenic hearts. Cardiac function was examined on the level of isolated cardiac myocytes, isolated organs and in intact animals. Whereas Ca2+ transients and cell shortening remained unchanged, L-type Ca2+ currents were decreased in isolated cardiac myocytes from transgenic mice. Ventricular contractility was reduced in isolated perfused hearts under basal conditions and after beta-adrenergic stimulation. In intact animals, echocardiography revealed increased left ventricular diameters and decreased contractility and invasively measured hemodynamic performance by left ventricular catheterization demonstrated a reduced response to beta-adrenergic stimulation in transgenic mice compared to wild type.Conclusions: Overexpression of PP5 affected contractility and beta-adrenergic signaling in the hearts of transgenic mice. Taken together, these findings are indicative of a regulatory role of PP5 in cardiac function. (C) 2010 Elsevier Ireland Ltd. All rights reserved.