Alterations in the heart mitochondrial proteome in a desmin null heart failure model
Alterations in the heart mitochondrial proteome in a desmin null heart failure model
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DOI：
10.1016/j.yjmcc.2004.12.008
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发表时间：
2005-03-01
影响因子：
5
通讯作者：
Capetanaki, Y
中科院分区：
文献类型：
--
作者：
Fountoulakis, M;Soumaka, E;Capetanaki, Y
结蛋白是一种重要的肌肉特异性中间丝蛋白，对线粒体的行为、功能和健康肌肉的维持至关重要。结蛋白缺失的小鼠发展为扩张型心肌病，其特征在于广泛的心肌细胞死亡、纤维化、钙化和最终的心力衰竭。我们试图研究野生型和结蛋白缺失小鼠的心脏线粒体蛋白质组，以了解结蛋白缺乏的心脏和骨骼肌病变表型。通过2-D电泳，然后通过基质辅助激光解吸/电离飞行时间质谱分析蛋白质。共鉴定出380种不同的基因产物，其中约50%为酶亚基。还鉴定了细胞骨架和肌肉特异性蛋白、钙结合蛋白、具有各种其他功能的蛋白以及大约70种未知的、假设的或描述不佳的基因产物。我们已经观察到大多数代谢途径的差异，在细胞凋亡，钙稳态，钙化和纤维化，并在不同的信号转导途径链接或不线粒体功能。在酮体和乙酸代谢、NADH穿梭蛋白、氨基酸代谢蛋白和呼吸酶中观察到最显著的变化。这些变化中的几个与已知的结蛋白缺乏症表型一致。(c)2005爱思唯尔有限公司保留所有权利。
Desmin, the major muscle-specific intermediate filament (IF) protein, is essential for mitochondrial behavior and function and maintenance of healthy muscle. Mice null for desmin develop dilated cardiomyopathy characterized by extensive cardiomyocyte death, fibrosis, calcification and eventual heart failure. We sought to investigate the heart mitochondrial proteome of wild type and desmin null mice in order to understand the cardiac and skeletal myopathy phenotype of desmin deficiency. The proteins were analyzed by 2-D electrophoresis, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Three hundred and eighty different gene products were identified, about 50% of which were enzyme subunits. Cytoskeletal and muscle-specific proteins, calcium-binding proteins, proteins with various other functions and about 70 unknown, hypothetical or poorly described gene products, were also identified. We have observed differences in most metabolic pathways, in apoptosis, calcium homeostasis, calcification and fibrosis and in different signaling pathways linked or not to mitochondrial function. The most significant changes were observed in ketone body and acetate metabolism, NADH shuttle proteins, amino-acid metabolism proteins and respiratory enzymes. Several of these changes are consistent with the known phenotype of desmin deficiency. (c) 2005 Elsevier Ltd. All rights reserved.