Myocardial infarction in mice alters sarcomeric function via post-translational protein modification.
Myocardial infarction in mice alters sarcomeric function via post-translational protein modification.
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DOI：
10.1007/s11010-011-1172-z
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发表时间：
2012-04
影响因子：
4.3
通讯作者：
Solaro, R. John
中科院分区：
文献类型：
--
作者：
Avner, Benjamin S.;Shioura, Krystyna M.;Scruggs, Sarah B.;Grachoff, Milana;Geenen, David L.;Helseth, Donald L., Jr.;Farjah, Mariam;Goldspink, Paul H.;Solaro, R. John
重塑前心肌梗死(MI)后的心肌生理学是一个未被充分研究的领域。在这里，我们描述心肌梗死对心脏肌节的影响，重点放在可能的贡献的活性氧(ROS)。我们结扎6-7月龄雌性CD1小鼠冠状动脉左前降支，造成心肌梗死。在心肌梗死或假手术(SH)后3-4天收集数据。超声心动图分析显示心肌梗死患者的室壁扩张和收缩功能障碍。心肌梗死心肌洗涤剂提取的乳头肌纤维束的亚最大钙激活张力显著增加。心肌梗死后钙敏感性增加，而激活的协同性降低。为了评估肌球蛋白酶的完整性，我们测量了肌原纤维制剂中CaATP的裂解，这表明肌丝肌球蛋白的CaATPase活性下降。生化分析证实了肌瘤蛋白的翻译后修饰。心肌梗死后乳头状肌标本中心肌肌钙蛋白I(CTnI)和肌球蛋白轻链2的磷酸化减少，这是用磷酸特异性染色测量的。原肌球蛋白在心肌梗死后被氧化，形成二硫化物，可通过斜线非还原-还原SDS-PAGE检测到。我们对心肌梗死后心肌蛋白氧化的分析也证实了S谷胱甘肽基化的增加。我们通过用巯基还原剂二硫苏糖醇处理皮肤纤维，在功能上将蛋白质氧化与肌节功能联系在一起，这降低了MI样本中的钙敏感性，而不是SH样本中的钙敏感性。我们的数据表明心肌梗死后心肌肌节的重要结构和功能改变，以及蛋白质氧化在这一过程中的作用。
Myocardial physiology in the aftermath of myocardial infarction (MI) before remodeling is an under-explored area of investigation. Here, we describe the effects of MI on the cardiac sarcomere with focus on the possible contributions of reactive oxygen species (ROS). We surgically induced MI in 6–7 month old female CD1 mice by ligation of the left anterior descending coronary artery. Data were collected 3–4 days after MI or sham surgery (SH). MI hearts demonstrated ventricular dilatation and systolic dysfunction upon echo cardiographic analysis. Sub-maximum Ca-activated tension in detergent extracted fiber bundles from papillary muscles increased significantly in the preparations from MI hearts. Ca++ sensitivity increased after MI, whereas cooperativity of activation decreased. To assess myosin enzymatic integrity we measured splitting of CaATP in myofibrillar preparations, which demonstrated a decline in CaATPase activity of myofilament myosin. Biochemical analysis demonstrated post-translational modification of sarcomeric proteins. Phosphorylation of cardiac troponin I (cTnI) and myosin light chain 2 was reduced after MI in papillary samples, as measured using a phospho-specific stain. Tropomyosin was oxidized after MI, forming disulfide products detectable by diagonal nonreducing-reducing SDS-PAGE. Our analysis of myocardial protein oxidation post-MI also demonstrated increased S-glutathionylation. We functionally linked protein oxidation with sarcomere function by treating skinned fibers with the sulfhydryl reducing agent dithiothreitol, which reduced Ca++ sensitivity in MI, but not SH, samples. Our data indicate important structural and functional alterations to the cardiac sarcomere after MI, and the contribution of protein oxidation to this process.
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影响因子：
5
作者：
Jacques, Adam M.;Copeland, O'Neal;Marston, Steven B.
通讯作者：
Marston, Steven B.
影响因子：
--
作者：
ALPERT, NR;GORDON, MS
通讯作者：
GORDON, MS
影响因子：
4.1
作者：
CLEMENT, O;PUCEAT, M;VASSORT, G
通讯作者：
VASSORT, G
影响因子：
2.7
作者：
Christopher, Bridgette;Pizarro, Gresin O.;Ogut, Ozgur
通讯作者：
Ogut, Ozgur
影响因子：
20.1
作者：
Doerries, Carola;Grote, Karsten;Landmesser, Ulf
通讯作者：
Landmesser, Ulf