Mechano-Chemo Transduction Tunes the Heartstrings
Mechano-Chemo Transduction Tunes the Heartstrings
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DOI：
10.1126/scisignal.2005214
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发表时间：
2014-03-18
影响因子：
7.3
通讯作者：
Ward, Christopher W.
中科院分区：
文献类型：
--
作者：
Prosser, Benjamin L.;Ward, Christopher W.
在跳动的心脏中，机械拉伸触发了靶向Ca 2+信号蛋白的活性氧或氮物质的产生。这条通路被称为机械化学转导，它“调节”健康心脏中的钙释放机制;当失调时，它会导致疾病。在这一期的《科学信号》中，Jian等人使用“细胞凝胶”方法表明，健康心脏细胞的收缩引起机械化学转导的急剧、粘度依赖性增加，其中一氧化氮合酶（NOS）、NADPH氧化酶2（Nox 2）和Ca 2 +/钙调蛋白依赖性激酶II（CaMK II）起作用。这些作者提供了神经元NOS（nNOS）在内皮NOS上的作用的证据;他们用超分辨率显微镜支持他们的发现，该显微镜将nNOS定位在离Ca 2+释放位点最近的地方。在疾病模型中，通过nNOS和CaMKII而不是通过Nox 2的信号传导增强，支持这些酶的独立机械活化。这些定量方法的耦合将提供一个新的理解力化学转导。
In the beating heart, mechanical stretch triggers the production of reactive oxygen or nitrogen species that target Ca2+- signaling proteins. Termed mechano-chemo transduction, this pathway "tunes" the calcium release machinery in the healthy heart; when dysregulated, it contributes to disease. In this issue of Science Signaling, Jian et al. used a "cell-in-gel" method to show that contractions in healthy heart cells elicit a steep, viscosity-dependent increase in mechano-chemo transduction in which nitric oxide synthase (NOS), NADPH oxidase 2 (Nox2), and Ca2+/calmodulin-dependent kinase II (CaMKII) contribute. These authors provide evidence for a role of neuronal NOS (nNOS) over endothelial NOS; they supported their findings with super-resolution microscopy, which localized nNOS nearest to the Ca2+ release sites. In a disease model, signaling through nNOS and CaMKII rather than through Nox2 was enhanced, supporting the independent mechanoactivation of these enzymes. The coupling of these quantitative approaches will provide a new understanding of mechano-chemo transduction.