X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin.
X-ROS Signaling Depends on Length-Dependent Calcium Buffering by Troponin.
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DOI：
10.3390/cells10051189
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发表时间：
2021-05-13
期刊：
影响因子：
6
通讯作者：
Jafri MS
中科院分区：
文献类型：
--
作者：
Limbu S;Prosser BL;Lederer WJ;Ward CW;Jafri MS
心肌细胞的伸展导致活性氧的产生增加，这通过称为X-ROS信号传导的过程增加了兰尼碱受体开放的可能性。肌细胞的拉伸也增加肌丝肌钙蛋白C的钙亲和力，这增加了其钙缓冲能力。在这里，一个综合性的实验和建模研究进行解释的肌钙蛋白和拉伸激活的X-ROS钙信号的钙缓冲的长度依赖性变化的相互作用。使用这种组合，我们表明，肌钙蛋白C依赖性增加肌细胞拉伸过程中的肌浆钙缓冲在很大程度上抵消了X-ROS依赖性增加从肌浆网钙释放。模型和实验的组合进一步通过在存在blebbistatin的情况下消除肌钙蛋白C钙结合的长度依赖性变化而被告知。在这里，该模型表明，这是X-ROS信号依赖性的Ca 2+释放增加，用于维持游离肌浆钙浓度在肌细胞长度的变化。总之，我们的实验和建模方法进一步确定了X-ROS信号传导和肌钙蛋白长度依赖性钙缓冲在塑造肌浆钙瞬变中的相对贡献。
The stretching of a cardiomyocyte leads to the increased production of reactive oxygen species that increases ryanodine receptor open probability through a process termed X-ROS signaling. The stretching of the myocyte also increases the calcium affinity of myofilament Troponin C, which increases its calcium buffering capacity. Here, an integrative experimental and modeling study is pursued to explain the interplay of length-dependent changes in calcium buffering by troponin and stretch-activated X-ROS calcium signaling. Using this combination, we show that the troponin C-dependent increase in myoplasmic calcium buffering during myocyte stretching largely offsets the X-ROS-dependent increase in calcium release from the sarcoplasmic reticulum. The combination of modeling and experiment are further informed by the elimination of length-dependent changes to troponin C calcium binding in the presence of blebbistatin. Here, the model suggests that it is the X-ROS signaling-dependent Ca2+ release increase that serves to maintain free myoplasmic calcium concentrations during a change in myocyte length. Together, our experimental and modeling approaches have further defined the relative contributions of X-ROS signaling and the length-dependent calcium buffering by troponin in shaping the myoplasmic calcium transient.
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影响因子：
7.3
作者：
Prosser, Benjamin L.;Ward, Christopher W.
通讯作者：
Ward, Christopher W.
影响因子：
--
作者：
Kaur, Sarbjot;Shen, Xin;Ward, Marie-Louise
通讯作者：
Ward, Marie-Louise
影响因子：
56.9
作者：
Prosser, Benjamin L.;Ward, Christopher W.;Lederer, W. J.
通讯作者：
Lederer, W. J.
影响因子：
--
作者：
BACKX, PH;TERKEURS, HEDJ
通讯作者：
TERKEURS, HEDJ
影响因子：
--
作者：
WANG, YP;FUCHS, F
通讯作者：
FUCHS, F