Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains.
Proteomic analysis of physiological versus pathological cardiac remodeling in animal models expressing mutations in myosin essential light chains.
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DOI：
10.1007/s10974-015-9434-0
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发表时间：
2015-12
影响因子：
2.7
通讯作者：
Szczesna-Cordary D
中科院分区：
文献类型：
--
作者：
Gomes AV;Kazmierczak K;Cheah JX;Gilda JE;Yuan CC;Zhou Z;Szczesna-Cordary D
在这项研究中，我们的目的是使用串联质量标签标记和液相色谱串联质谱法对病理和生理性心脏肥大的转基因小鼠模型的心脏中差异表达的蛋白质进行深入的蛋白质组学分析。表达 43 个氨基酸 N 端截短的肌球蛋白必需轻链 (ELC) 的 Δ43 小鼠模型可作为研究生理性心脏重塑机制的工具，同时在 A57G（丙氨酸 57 → 甘氨酸）ELC 小鼠中研究病理性肥大。结果显示，通过突变体与野生型 (WT) 样品的多对比较确定，30 种蛋白质在 Δ43 与 A57G 心脏中存在差异表达，P < 0.05。当将两个突变体与 WT 心脏进行比较时，A57G 心脏显示出参与代谢过程的 9 种线粒体蛋白的差异表达，而 Δ43 心脏中的 4 种蛋白则表现出差异表达。 Δ43 和 A57G 心脏之间的比较显示，Δ43 心脏中三种代谢重要的线粒体蛋白上调，但九种蛋白质下调。心脏肥大的生理模型(Δ43)显示Ca2+结合蛋白的水平相对于WT没有变化，而病理模型(A57G)显示三种Ca2+结合蛋白的上调，包括肌钙蛋白。在 Δ43 与 A57G 心脏中还观察到分子伴侣和脂肪酸代谢蛋白的独特差异。蛋白质组学数据支持之前对两种心脏肥大动物模型进行的功能研究的结果，并表明 A57G 而非 Δ43 介导的脂肪酸代谢和 Ca2+ 稳态的改变可能有助于 A57G 心脏的病理性心脏重塑。
In this study we aimed to provide an in-depth proteomic analysis of differentially expressed proteins in the hearts of transgenic mouse models of pathological and physiological cardiac hypertrophy using tandem mass tag labeling and liquid chromatography tandem mass spectrometry. The Δ43 mouse model, expressing the 43-amino-acid N-terminally truncated myosin essential light chain (ELC) served as a tool to study the mechanisms of physiological cardiac remodeling, while the pathological hypertrophy was investigated in A57G (Alanine 57 → Glycine) ELC mice. The results showed that 30 proteins were differentially expressed in Δ43 versus A57G hearts as determined by multiple pair comparisons of the mutant versus wild-type (WT) samples with P < 0.05. The A57G hearts showed differential expression of nine mitochondrial proteins involved in metabolic processes compared to four proteins for Δ43 hearts when both mutants were compared to WT hearts. Comparisons between Δ43 and A57G hearts showed an upregulation of three metabolically important mitochondrial proteins but downregulation of nine proteins in Δ43 hearts. The physiological model of cardiac hypertrophy (Δ43) showed no changes in the levels of Ca2+-binding proteins relative to WT, while the pathologic model (A57G) showed the upregulation of three Ca2+-binding proteins, including sarcalumenin. Unique differences in chaperone and fatty acid metabolism proteins were also observed in Δ43 versus A57G hearts. The proteomics data support the results from functional studies performed previously on both animal models of cardiac hypertrophy and suggest that the A57G- and not Δ43- mediated alterations in fatty acid metabolism and Ca2+ homeostasis may contribute to pathological cardiac remodeling in A57G hearts.