Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.
Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.
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DOI：
10.3389/fcvm.2022.1060716
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发表时间：
2022
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
发现心脏肌节蛋白是S-谷胱甘肽化的底物，并且这种翻译后修饰与舒张功能障碍密切相关，这导致了关于氧化应激水平如何影响心跳的新概念。存在S-谷胱甘肽化证据的主要肌节蛋白包括心肌肌球蛋白结合蛋白C（cMyBP-C）、肌动蛋白、心肌肌钙蛋白I（cTnI）和肌联蛋白。我们的假设是，这些S-谷胱甘肽化的蛋白质是获得性和家族性心脏疾病的重要因素，并在释放到血清中时，提供新的生物标志物。我们认为，这些影响的分子机制的背景下，最近的启示，这些蛋白质如何控制心脏动力学与Ca 2+通量密切合作。这些发现是使用强大的方法和技术完成的，这些方法和技术专注于细纤维，粗纤维和titin纤维。在这里，我们将其调节过程中的肌节调制主要由神经体液控制磷酸化，因为证据表明，S-谷胱甘肽和蛋白质磷酸化，促进增加动力学和修改的弗兰克-斯塔林关系，可能是相互排斥的。早期研究表明，除了cTnI作为心脏疾病的公认生物标志物外，血清cMyBP-C水平也是心脏疾病的生物标志物。我们描述了最近的研究，探讨血清S-谷胱甘肽-cMyBP-C水平是否可以作为一个重要的临床工具，在患者分层，早期诊断HFpEF前的风险患者，确定进展，有效的治疗方法，并作为指导，在开发未来的治疗方法。
The discovery that cardiac sarcomere proteins are substrates for S-glutathionylation and that this post-translational modification correlates strongly with diastolic dysfunction led to new concepts regarding how levels of oxidative stress affect the heartbeat. Major sarcomere proteins for which there is evidence of S-glutathionylation include cardiac myosin binding protein C (cMyBP-C), actin, cardiac troponin I (cTnI) and titin. Our hypothesis is that these S-glutathionylated proteins are significant factors in acquired and familial disorders of the heart; and, when released into the serum, provide novel biomarkers. We consider the molecular mechanisms for these effects in the context of recent revelations of how these proteins control cardiac dynamics in close collaboration with Ca2+ fluxes. These revelations were made using powerful approaches and technologies that were focused on thin filaments, thick filaments, and titin filaments. Here we integrate their regulatory processes in the sarcomere as modulated mainly by neuro-humoral control of phosphorylation inasmuch evidence indicates that S-glutathionylation and protein phosphorylation, promoting increased dynamics and modifying the Frank-Starling relation, may be mutually exclusive. Earlier studies demonstrated that in addition to cTnI as a well-established biomarker for cardiac disorders, serum levels of cMyBP-C are also a biomarker for cardiac disorders. We describe recent studies approaching the question of whether serum levels of S-glutathionylated-cMyBP-C could be employed as an important clinical tool in patient stratification, early diagnosis in at risk patients before HFpEF, determination of progression, effectiveness of therapeutic approaches, and as a guide in developing future therapies.
DOI：
10.1016/j.amjcard.2017.07.042
发表时间：
2017-11-01
期刊：
The American journal of cardiology
影响因子：
--
作者：
Tong CW;Dusio GF;Govindan S;Johnson DW;Kidwell DT;De La Rosa LM;Rosas PC;Liu Y;Ebert E;Newell-Rogers MK;Michel JB;Trzeciakowski JP;Sadayappan S
通讯作者：
Sadayappan S
DOI：
10.1085/jgp.201711974
发表时间：
2018-06-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Reda SM;Chandra M
通讯作者：
Chandra M
影响因子：
4.5
作者：
Mamidi, Ranganath;Li, Jiayang;Gresham, Kenneth S.;Stelzer, Julian E.
通讯作者：
Stelzer, Julian E.