Reversal of diabetes-evoked changes in mitochondrial protein expression of cardiac left ventricle by treatment with a copper (II)-selective chelator

Mia Jüllig, Xiuyin Chen, Anthony J. Hickey, David J. Crossman, Aimin Xu, Yu Wang, David R. Greenwood, Yee Soon Choong, Sarah J. Schönberger, Martin J. Middleditch, Anthony R J Phillips, Garth Cooper

Research output: Contribution to journalArticlepeer-review

Abstract

Cardiac disease is the commonest cause of death amongst diabetic patients. Diabetic cardiomyopathy, which has a poor prognosis, is characterized by left ventricular hypertrophy and impaired cardiac function and mitochondrial damage is said to contribute to its development. We recently showed that treatment with the CuII-selective chelator, triethylenetetramine (TETA), improved cardiac structure, and function in diabetic subjects without modifying hyperglycemia. Thus, TETA has potential utility for the treatment of heart disease. To further understand the molecular mechanism by which it causes these effects, we have conducted the first study of the effect of oral TETA on protein abundance in the cardiac left ventricle of rats with severe streptozotocin-induced diabetes. Proteomic methods showed that of 211 proteins changed in diabetes, 33 recovered after treatment. Through MS, 16 proteins were identified which may constitute major targets of drug action. Remarkably, most of these were mitochondrial proteins with Toles in energy metabolism. In addition to components of the mitochondrial respiratory chain and enzymes involved in fatty add oxidation, TETA treatment normalized both myocardial expression and enzymatic activity of carnitine palmitoyltransferase 2. These findings indicate that mitochondria constitute major targets in the mechanism by which TETA restores cardiac structure and function in diabetes. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Original languageEnglish
Pages (from-to)387-399
Number of pages12
JournalProteomics - Clinical Applications
Volume1
Issue number4
DOIs
Publication statusPublished - Apr 2007

Keywords

  • Diabetic cardiomyopathy
  • Diabetic complications
  • Diastolic heart failure
  • Electron transport chain
  • Left ventricular hypertrophy

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