Phosphoproteomic response of cardiac endothelial cells to ischemia and ultrasound.
Phosphoproteomic response of cardiac endothelial cells to ischemia and ultrasound.
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心脏内皮细胞对缺血和超声的磷酸化蛋白质组学反应
DOI：
10.1016/j.bbapap.2021.140683
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发表时间：
2021-09
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影响因子：
--
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中科院分区：
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心肌梗死及后续的治疗干预会激活心脏每种组成细胞类型中的众多细胞内级联反应。在常氧和缺血条件下，内皮细胞在治疗性超声作用下会产生几种保护性化合物。内皮细胞如何感知超声并将其转化为有益的生物学反应尚不清楚。我们采用了一种全面、无偏的磷酸化蛋白质组学方法，旨在了解内皮细胞对超声的反应。在此，我们使用原代心脏内皮细胞在体外探索对类缺血性细胞损伤和超声暴露的反应所涉及的细胞信号传导事件。利用高精度液相色谱（LC） - 串联质谱（MS/MS）蛋白质组学平台对富集的磷酸肽进行分析，发现缺血性损伤和超声作用下总蛋白水平和磷酸化事件均发生多种改变。通路算法的应用揭示了超声作用下招募的众多蛋白质网络，包括那些调控RNA剪接、细胞 - 细胞相互作用和细胞骨架组织的网络。我们的数据集还允许对检测到的修饰所涉及的潜在激酶进行信息学预测。综上所述，我们的研究结果开始揭示内皮细胞对超声的蛋白质组学反应，并为未来研究超声在缺血心脏中的保护作用提出了潜在靶点。
Myocardial infarction and subsequent therapeutic interventions activate numerous intracellular cascades in every constituent cell type of the heart. Endothelial cells produce several protective compounds in response to therapeutic ultrasound, under both normoxic and ischemic conditions. How endothelial cells sense ultrasound and convert it to a beneficial biological response is not known. We adopted a global, unbiased phosphoproteomics approach aimed at understanding how endothelial cells respond to ultrasound. Here, we use primary cardiac endothelial cells to explore the cellular signaling events underlying the response to ischemia-like cellular injury and ultrasound exposure in vitro. Enriched phosphopeptides were analyzed with a high mass accuracy liquid chromatrography (LC) - tandem mass spectrometry (MS/MS) proteomic platform, yielding multiple alterations in both total protein levels and phosphorylation events in response to ischemic injury and ultrasound. Application of pathway algorithms reveals numerous protein networks recruited in response to ultrasound including those regulating RNA splicing, cell-cell interactions and cytoskeletal organization. Our dataset also permits the informatic prediction of potential kinases responsible for the modifications detected. Taken together, our findings begin to reveal the endothelial proteomic response to ultrasound and suggest potential targets for future studies of the protective effects of ultrasound in the ischemic heart.
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5.8
作者：
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通讯作者：
Birukov, Konstantin G.
DOI：
10.1073/pnas.0611510104
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影响因子：
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作者：
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影响因子：
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作者：
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