Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.
Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.
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DOI：
10.1371/journal.pone.0104157
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bowles DE
中科院分区：
文献类型：
--
作者：
Schechter MA;Hsieh MK;Njoroge LW;Thompson JW;Soderblom EJ;Feger BJ;Troupes CD;Hershberger KA;Ilkayeva OR;Nagel WL;Landinez GP;Shah KM;Burns VA;Santacruz L;Hirschey MD;Foster MW;Milano CA;Moseley MA;Piacentino V 3rd;Bowles DE
The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.
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影响因子：
4.8
作者：
KOROTCHKINA, LG;PATEL, MS
通讯作者：
PATEL, MS
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DOI：
10.1016/j.bbrc.2012.02.049
发表时间：
2012-03-16
影响因子：
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作者：
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