https://scholars.lib.ntu.edu.tw/handle/123456789/416698
標題: | Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice | 作者: | Hung, C.-L. SZU-HUA PAN Han, C.-L. Chang, C.-W. Hsu, Y.-L. Su, C.-H. Shih, S.-C. Lai, Y.-J. Chiau, J.-S.C. Yeh, H.-I. Liu, C.-Y. Lee, H.-C. Lam, C.S.P. |
關鍵字: | Cytoskeletal proteins | Diabetic cardiomyopathy | F-actin | G-actin | High fat diet | ITRAQ membrane proteomic profiling | Oxidative phosphorylation | Type 2 diabetes (T2DM);Cytoskeletal proteins; Diabetic cardiomyopathy; F-actin; G-actin; High fat diet; ITRAQ membrane proteomic profiling; Oxidative phosphorylation; Type 2 diabetes (T2DM) | 公開日期: | 2017 | 出版社: | AMER CHEMICAL SOC | 卷: | 16 | 期: | 10 | 起(迄)頁: | 3504 | 來源出版物: | Journal of Proteome Research | 摘要: | © 2017 American Chemical Society. Diabetic cardiomyopathy is a well-recognized complication of diabetes, but its pathophysiology is unclear. We aimed to investigate the mechanisms underlying cardiac dysfunction in an elderly type 2 diabetic (T2DM) mouse model, using membrane proteomic analyses. Elderly mice were fed a high fat diet for 12 weeks to induce T2DM, and myocardial structure and function were assessed by echocardiography. Cardiomyocytes were isolated by Langendorff perfusion and subjected to iTRAQ-based quantitative membrane proteomic profiling, immunoblotting, and real-time quantitative reverse-transcriptase polymerase chain reaction. Compared to controls, elderly T2DM mice showed worse systolic function, more myocardial fibrosis and up-regulation of several heart failure markers (all p < 0.05). Cardiomyocyte membrane proteomic profiling revealed that 417 proteins had differential expressions related to perturbations in several biological processes in T2DM mice compared with the control. The most up-regulated proteins were involved in oxidative phosphorylation, whereas many down-regulated proteins were involved in cytoskeletal regulation. Differential protein expression correlated with myocardial systolic velocity by tissue Doppler. In addition, cardiomyocyte immunofluorescence staining showed greater disorganization of thick/parallel F-actin stress fibers and marked reduction in F-to-G-actin ratio in T2DM vs control (p < 0.05), which paralleled worsened myocardial systolic velocity. We concluded that cardiac contractile dysfunction in elderly T2DM mice was associated with impaired energetics and cytoskeletal disorganization. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-85044110620&partnerID=MN8TOARS https://scholars.lib.ntu.edu.tw/handle/123456789/416698 |
ISSN: | 1535-3893 1535-3907 |
DOI: | 10.1021/acs.jproteome.7b00148 60947662 |
SDG/關鍵字: | biological marker; collagen type 1; F actin; G actin; glucagon like peptide 1; glucagon like peptide 1 receptor; actin; membrane protein; animal cell; animal experiment; animal model; animal tissue; Article; cardiac muscle cell; controlled study; cytoskeleton; diabetic cardiomyopathy; echocardiography; energy transfer; heart failure; heart muscle contractility; heart muscle fibrosis; immunoblotting; immunofluorescence; isolated heart; lipid diet; liquid chromatography-mass spectrometry; male; mouse; non insulin dependent diabetes mellitus; nonhuman; oxidative phosphorylation; priority journal; protein expression; proteomics; quantitative analysis; real time polymerase chain reaction; reverse transcription polymerase chain reaction; stress fiber; systole; tissue Doppler imaging; upregulation; animal; cardiac muscle; complication; cytoskeleton; disease model; energy metabolism; fibrosis; gene expression regulation; genetics; human; metabolism; non insulin dependent diabetes mellitus; pathology; Actins; Animals; Cytoskeleton; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Fibrosis; Gene Expression Regulation; Humans; Membrane Proteins; Mice; Myocardium; Myocytes, Cardiac; Proteomics |
顯示於: | 基因體暨蛋白體醫學研究所 |
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