|Title:||Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice||Authors:||Hung, C.-L.
|Keywords:||Cytoskeletal proteins | Diabetic cardiomyopathy | F-actin | G-actin | High fat diet | ITRAQ membrane proteomic profiling | Oxidative phosphorylation | Type 2 diabetes (T2DM)||Issue Date:||2017||Publisher:||AMER CHEMICAL SOC||Journal Volume:||16||Journal Issue:||10||Start page/Pages:||3504||Source:||Journal of Proteome Research||Abstract:||
© 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.
|Appears in Collections:||基因體暨蛋白體醫學研究所|
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