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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, YuanLing Hsu, Cheng-Huang Su, Shou-Chuan Shih, Yu-Jun Lai, Jen-Shiu Chiang Chiau, Hung-I Yeh, Chia-Yuan Liu, Hung-Chang Lee, and Carolyn S.P. Lam J. Proteome Res., Just Accepted Manuscript • DOI: 10.1021/acs.jproteome.7b00148 • Publication Date (Web): 20 Aug 2017 Downloaded from http://pubs.acs.org on August 22, 2017
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Journal of Proteome Research is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
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Journal of Proteome Research
Membrane Proteomics of Impaired Energetics and Cytoskeletal Disorganization in Elderly Diet-Induced Diabetic Mice Chung-Lieh Hung1, 2, 3δ, Szu-Hua Pan4, 5, 6δ, Chia-Li Han7, 8, Ching-Wei Chang1,9,15, Yuan-Ling Hsu4, Cheng-Huang Su2, 3, Shou-Chuan Shih1,9, Yu-Jun Lai1, Jen-Shiu Chiang Chiau10, Hung-I Yeh1, , Chia-Yuan Liu1,9,15 *, Hung-Chang Lee1,11,12,13, Carolyn S.P. Lam14
3*
1.
Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan;
2.
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan;
3.
Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan;
4.
Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei 100, Taiwan;
5.
Doctoral Degree Program of Translational Medicine, National Taiwan University and Academia Sinica, Taipei 100, Taiwan;
6.
Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 100, Taiwan;
7.
Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan;
8.
Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan;
9.
Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 104, Taiwan
10. Department of Medicine Research, Hsinchu MacKay Memorial Hospital, Hsinchu City 30071, Taiwan; 11. MacKay Children’s Hospital, Taipei 104, Taiwan; 12. MacKay Junior College of Medicine, Nursing, and Management, New Taipei City 252, Taiwan; 13. Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu City 30071, Taiwan; 14. National Heart Centre Singapore and Duke-National University of Singapore 15. Institute of Traditional Medicine, National Yang-Ming University, Taipei 112, Taiwan δ These authors equally contributed to this project
*Correspondence to: Dr. Chia-Yuan Liu (
[email protected]) and Dr. Hung-I Yeh (
[email protected]). Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Chung-Shan North Road, 2nd Section, Taipei, Taiwan (TEL: 886-2-2531-9260, FAX: 886-2-2543-3535-2459). Abbreviated Title: Membrane Proteomics in Diabetic Cardiomyopathy 1
ACS Paragon Plus Environment
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TABLE OF CONTENTS Abstract -----------------------------------------------------------------------------
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Introduction ------------------------------------------------------------------------
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Experimental Section -------------------------------------------------------------
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Results ------------------------------------------------------------------------------
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Discussion --------------------------------------------------------------------------
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Conclusion -------------------------------------------------------------------------
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Associated content ----------------------------------------------------------------
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Acknowledgements ---------------------------------------------------------------
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Conflic of interests ----------------------------------------------------------------
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Author contributions--------------------------------------------------------------- 16 Ethical approval -------------------------------------------------------------------
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Fundings ----------------------------------------------------------------------------
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References -------------------------------------------------------------------------- 17 Figure legends ---------------------------------------------------------------------
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Graphic abstract -------------------------------------------------------------------
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Journal of Proteome Research
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 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
