首页> 外文会议>American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics >Top-Down Proteomics Identified Upregulated PKC Phosphorylation Sites of Cardiac Troponin I in Spontaneously Hypertensive Heart Failure Rat
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Top-Down Proteomics Identified Upregulated PKC Phosphorylation Sites of Cardiac Troponin I in Spontaneously Hypertensive Heart Failure Rat

机译:自上而下的蛋白质组学鉴定了在自发性高血压性心力衰竭大鼠中的心肌肌钙蛋白I的上调PKC磷酸化位点

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Our top-down proteomics approach, which combined immunoaffinity chromatography, high resolution top-down MS and Western blotting, showed up-regulation of PKC and PKC-mediated phosphorylation of cTnI and suggest a significant role in the progression and development of hypertensive heart failure in SHR. We have detected increased Ser43/45 phosphorylation, in addition to Ser23/24, in the SHR-HF. The top-down MS with ECD has its unique advantage of comprehensive and unbiased analysis of labile phosphorylation including the reliable detection, quantitation, and mapping of the phosphorylation sites. Collectively our results suggests that cTnI exists in a hyperphosphorylation state in hypertensive heart failure, which is attributable, in part, to increased activity and signaling of PKC-alpha and -delta. This study provides the first direct evidence of in situ PKC phosphorylation in cTnI from a heart failure animal model suggesting that PKC phosphorylation at Ser43/45 is maladaptive and is associated with cardiac dysfunction in heart failure.
机译:我们的自上而下的蛋白质组学方法,其组合免疫亲和性色谱,高分辨率降压MS和Western印迹,表现出PKC和PKC介导的CTNI磷酸化的上调,并表明了高血压心力衰竭的进展和发展中的重要作用SHR。除了SHR-HF中,除了SER23 / 24之外,我们还检测到SER43 / 45磷酸化增加。与ECD的自上而下的MS具有其独特的优势,可以综合和无偏磷酸化分析,包括可靠的检测,定量和磷酸化位点的测绘。统称我们的结果表明CTNI在高血压心力衰竭中存在于高血磷酸化状态,其可归因于增加PKC-α和-Delta的活性和信号传导。该研究提供了来自心力衰竭动物模型的CTNI中原位PKC磷酸化的第一种直接证据,表明SER43 / 45的PKC磷酸化是不良的,并且与心力衰竭心脏功能障碍有关。

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