Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rat with heart failure
Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rat with heart failure
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DOI：
10.1152/ajpheart.00562.2007
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发表时间：
2007-10-01
影响因子：
4.8
通讯作者：
Wehrens, Xander H. T.
中科院分区：
文献类型：
--
作者：
Chen-Izu, Ye;Ward, Christopher W.;Wehrens, Xander H. T.
作为了解高血压诱导的心肌肥厚和心力衰竭发展过程中通过ryanodine受体（RyR（2））的异常细胞内Ca 2+释放的作用的关键一步，本研究探讨了两个问题：1）在肥厚和心力衰竭发展的哪个阶段，如果有的话，RyR（2）在Ser（2808）处过度磷酸化？2)心力衰竭时RyR（2）簇的空间分布是否会发生变化？使用一种新开发的半定量免疫组化方法和蛋白质印迹法，我们测量磷酸化RyR2在Ser2808在自发性高血压大鼠（SHR）在四个不同的疾病阶段。一个主要的发现是RyR（2）在Ser（2808）的过度磷酸化仅发生在SHR的晚期心力衰竭中，而不是在年龄匹配的对照中。此外，RyR2簇之间的间距缩短在衰竭的心脏，如定量模型模拟预测，增加自发性Ca2+波的产生和心律失常。
As a critical step toward understanding the role of abnormal intracellular Ca2+ release via the ryanodine receptor (RyR(2)) during the development of hypertension-induced cardiac hypertrophy and heart failure, this study examines two questions: 1) At what stage, if ever, in the development of hypertrophy and heart failure is RyR(2) hyperphosphorylated at Ser(2808)? 2) Does the spatial distribution of RyR(2) clusters change in failing hearts? Using a newly developed semiquantitative immunohistochemistry method and Western blotting, we measured phosphorylation of RyR2 at Ser2808 in the spontaneously hypertensive rat (SHR) at four distinct disease stages. A major finding is that hyperphosphorylation of RyR(2) at Ser(2808) occurred only at late-stage heart failure in SHR, but not in age- matched controls. Furthermore, the spacing between RyR2 clusters was shortened in failing hearts, as predicted by quantitative model simulation to increase spontaneous Ca2+ wave generation and arrhythmias.