Effect of spatial heterogeneity and colocalization of eNOS and capacitative calcium entry channels on shear stress-induced NO production by endothelial cells: A modeling approach.
Effect of spatial heterogeneity and colocalization of eNOS and capacitative calcium entry channels on shear stress-induced NO production by endothelial cells: A modeling approach.
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DOI：
10.1007/s12195-018-0520-4
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发表时间：
2018-04
影响因子：
2.8
通讯作者：
Jaron D
中科院分区：
文献类型：
--
作者：
Barbee KA;Parikh JB;Liu Y;Buerk DG;Jaron D
内皮型一氧化氮合酶（eNOS）和容性Ca2+进入（CCE）通道在内皮细胞（ECs）微域（如cavaeolae）中的共定位已被证明可以显著影响细胞内Ca2+动力学和NO的产生，但这种影响尚未得到很好的量化。我们建立了一个二维连续体模型，整合了剪切应力介导的ATP产生、细胞内Ca2+动员和eNOS激活，以研究在流动诱导的剪切应力下，质膜eNOS和CCE通道的空间共定位对Ca2+动力学和NO产生的影响。我们的模型检验了细胞成分的亚细胞共定位对于NO生产与血流的最佳耦合至关重要的假设。我们的模拟预测CCE的异质性可以导致微域的形成，与平均细胞质Ca2+相比，Ca2+明显更高。相对于可移动缓冲液，低迁移率或无迁移率的Ca2+缓冲液进一步增强了Ca2+梯度。eNOS与CCE通道的共定位显著增加了NO的产生。我们的研究结果为空间异质性和信号分区在剪切应力诱导的NO生成调控中的作用提供了定量理解。
Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca2+ entry (CCE) channels in microdomains such as cavaeolae in endothelial cells (ECs) has been shown to significantly affect intracellular Ca2+ dynamics and NO production, but the effect has not been well quantified. We developed a two-dimensional continuum model of an EC integrating shear stress-mediated ATP production, intracellular Ca2+ mobilization, and eNOS activation to investigate the effects of spatial colocalization of plasma membrane eNOS and CCE channels on Ca2+ dynamics and NO production in response to flow-induced shear stress. Our model examines the hypothesis that subcellular colocalization of cellular components can be critical for optimal coupling of NO production to blood flow. Our simulations predict that heterogeneity of CCE can result in formation of microdomains with significantly higher Ca2+ compared to the average cytosolic Ca2+. Ca2+ buffers with lower or no mobility further enhanced Ca2+ gradients relative to mobile buffers. Colocalization of eNOS to CCE channels significantly increased NO production. Our results provide quantitative understanding for the role of spatial heterogeneity and the compartmentalization of signals in regulation of shear stress-induced NO production.
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DOI：
10.1016/j.niox.2010.08.003
发表时间：
2010-12-15
期刊：
Nitric oxide : biology and chemistry
影响因子：
--
作者：
Andrews AM;Jaron D;Buerk DG;Kirby PL;Barbee KA
通讯作者：
Barbee KA
影响因子：
4.8
作者：
Fulton, D;Babbitt, R;Sessa, WC
通讯作者：
Sessa, WC
影响因子：
1.7
作者：
Helmlinger, G;Berk, BC;Nerem, RM
通讯作者：
Nerem, RM
影响因子：
20.1
作者：
Francis M;Waldrup JR;Qian X;Solodushko V;Meriwether J;Taylor MS
通讯作者：
Taylor MS
影响因子：
3.7
作者：
Béliveau É;Lessard V;Guillemette G
通讯作者：
Guillemette G