Proteomic analysis of metabolic, cytoskeletal and stress response proteins in human heart failure.

Proteomic analysis of metabolic, cytoskeletal and stress response proteins in human heart failure.
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人类心力衰竭代谢、细胞骨架和应激反应蛋白的蛋白质组学分析

DOI:
10.1111/j.1582-4934.2011.01336.x
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发表时间:
2012-01
影响因子:
5.3
通讯作者:
Du J
Du J
中科院分区:
医学2区
文献类型:
--
作者:
Li W;Rong R;Zhao S;Zhu X;Zhang K;Xiong X;Yu X;Cui Q;Li S;Chen L;Cai J;Du J

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人类心力衰竭是一种复杂的综合征,是世界范围内发病和死亡的主要原因。然而,参与重塑过程的分子途径知之甚少。在这项研究中,我们对从衰竭和非衰竭人类心脏中分离的心室进行了详尽的全球蛋白质组学调查,并确定了揭示心力衰竭机制的调控途径。使用二维凝胶电泳(2-DE)结合串联质谱法鉴定衰竭(n = 9)和非衰竭(n = 6)人心脏标本中差异表达的蛋白质。  共鉴定出25种在衰竭心脏中变化至少1.5倍的蛋白质; 15种蛋白质上调,10种蛋白质下调。改变的蛋白质属于三大功能类别:(i)代谢[如NADH脱氢酶(泛醌)、二氢硫辛酰胺脱氢酶和细胞色素c氧化酶亚基];(ii)细胞骨架(如肌球蛋白轻链蛋白、肌钙蛋白I 3型和甲状腺素运载蛋白)和(iii)应激反应(如αB-晶状体蛋白、HSP 27和HSP 20)。   Western blot进一步证实了所选蛋白质(包括HSP 27和HSP 20)表达的显著差异。因此,我们对人类心力衰竭中的蛋白质变化进行了全面筛选,并对可能在心功能不全中至关重要的蛋白质进行了分析,以供将来作图。
Human heart failure is a complex syndrome and a primary cause of morbidity and mortality in the world. However, the molecular pathways involved in the remodelling process are poorly understood. In this study, we performed exhaustive global proteomic surveys of cardiac ventricle isolated from failing and non‐failing human hearts, and determined the regulatory pathway to uncover the mechanism underlying heart failure. Two‐dimensional gel electrophoresis (2‐DE) coupled with tandem mass spectrometry was used to identify differentially expressed proteins in specimens from failing (n = 9) and non‐failing (n = 6) human hearts. A total of 25 proteins with at least 1.5‐fold change in the failing heart were identified; 15 proteins were up‐regulated and 10 proteins were down‐regulated. The altered proteins belong to three broad functional categories: (i) metabolic [e.g. NADH dehydrogenase (ubiquinone), dihydrolipoamide dehydrogenase, and the cytochrome c oxidase subunit]; (ii) cytoskeletal (e.g. myosin light chain proteins, troponin I type 3 and transthyretin) and (iii) stress response (e.g. αB‐crystallin, HSP27 and HSP20). The marked differences in the expression of selected proteins, including HSP27 and HSP20, were further confirmed by Western blot. Thus, we carried out full‐scale screening of the protein changes in human heart failure and profiled proteins that may be critical in cardiac dysfunction for future mapping.
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