Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice

Chung Lieh Hung, Szu Hua Pan, Chia Li Han, Ching Wei Chang, Yuan Ling Hsu, Cheng Huang Su, Shou Chuan Shih, Yu Jun Lai, Jen Shiu Chiang Chiau, Hung I. Yeh, Chia Yuan Liu, Hung Chang Lee, Carolyn S.P. Lam

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4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3504-3513
Number of pages10
JournalJournal of Proteome Research
Volume16
Issue number10
DOIs
Publication statusPublished - Oct 6 2017

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Keywords

  • Cytoskeletal proteins
  • Diabetic cardiomyopathy
  • F-actin
  • G-actin
  • High fat diet
  • ITRAQ membrane proteomic profiling
  • Oxidative phosphorylation
  • Type 2 diabetes (T2DM)

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Hung, C. L., Pan, S. H., 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. (2017). Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice. Journal of Proteome Research, 16(10), 3504-3513. https://doi.org/10.1021/acs.jproteome.7b00148