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

Research output: Contribution to journalArticle

3 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

Fingerprint

Diabetic Diet
Nutrition
Proteomics
Membranes
Cardiac Myocytes
Actins
Proteins
Echocardiography
Diabetic Cardiomyopathies
Polymerase chain reaction
RNA-Directed DNA Polymerase
Biological Phenomena
Medical problems
Stress Fibers
Oxidative Phosphorylation
High Fat Diet
Diabetes Complications
Reverse Transcriptase Polymerase Chain Reaction
Immunoblotting
Fats

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

Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice. / Hung, Chung Lieh; Pan, Szu Hua; Han, Chia Li; Chang, Ching Wei; Hsu, Yuan Ling; Su, Cheng Huang; Shih, Shou Chuan; Lai, Yu Jun; Chiau, Jen Shiu Chiang; Yeh, Hung I.; Liu, Chia Yuan; Lee, Hung Chang; Lam, Carolyn S.P.

In: Journal of Proteome Research, Vol. 16, No. 10, 06.10.2017, p. 3504-3513.

Research output: Contribution to journalArticle

Hung, CL, Pan, SH, Han, CL, Chang, CW, Hsu, YL, Su, CH, Shih, SC, Lai, YJ, Chiau, JSC, Yeh, HI, Liu, CY, Lee, HC & Lam, CSP 2017, 'Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice', Journal of Proteome Research, vol. 16, no. 10, pp. 3504-3513. https://doi.org/10.1021/acs.jproteome.7b00148
Hung, Chung Lieh ; Pan, Szu Hua ; Han, Chia Li ; Chang, Ching Wei ; Hsu, Yuan Ling ; Su, Cheng Huang ; Shih, Shou Chuan ; Lai, Yu Jun ; Chiau, Jen Shiu Chiang ; Yeh, Hung I. ; Liu, Chia Yuan ; Lee, Hung Chang ; Lam, Carolyn S.P. / Membrane proteomics of impaired energetics and cytoskeletal disorganization in elderly diet-induced diabetic mice. In: Journal of Proteome Research. 2017 ; Vol. 16, No. 10. pp. 3504-3513.
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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.",
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AU - Pan, Szu Hua

AU - Han, Chia Li

AU - Chang, Ching Wei

AU - Hsu, Yuan Ling

AU - Su, Cheng Huang

AU - Shih, Shou Chuan

AU - Lai, Yu Jun

AU - Chiau, Jen Shiu Chiang

AU - Yeh, Hung I.

AU - Liu, Chia Yuan

AU - Lee, Hung Chang

AU - Lam, Carolyn S.P.

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N2 - 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.

AB - 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.

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KW - G-actin

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KW - Type 2 diabetes (T2DM)

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