Quantitative protein profiling in heart mitochondria from diabetic rats
Illarion V Turko1, Ferid Murad
1Department of Integrative Biology and Pharmacology and Institute of Molecular Medicine, University of Texas Medical School, Houston, Texas 77030, USA.
The Journal of Biological Chemistry
|July 10, 2003
Summary
Diabetes rapidly alters heart mitochondria protein expression, favoring fatty acid oxidation over glucose and decreasing electron transport proteins. These changes in mitochondrial function occur early after diabetes onset.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background:
- Diabetes mellitus is a metabolic disorder with significant cardiovascular complications.
- Mitochondrial dysfunction plays a crucial role in the pathogenesis of diabetic cardiomyopathy.
- Understanding diabetes-induced changes in cardiac mitochondrial proteome is essential for developing therapeutic strategies.
Purpose of the Study:
- To investigate the alterations in cardiac mitochondrial protein expression in a rat model of diabetes.
- To identify specific proteins and pathways affected by diabetes in heart mitochondria.
- To determine the temporal profile of these changes following diabetes induction.
Main Methods:
- Quantitative protein profiling using in vitro stable isotope labeling.
- Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) for protein separation.
- Mass spectrometry (MS) for protein identification and quantification.
- Streptozotocin-induced diabetes model in rats.
Main Results:
- No significant alteration in myocardial tricarboxylic acid cycle proteins.
- Up-regulation of fatty acid beta-oxidation proteins, favoring fatty acids over glucose for acetyl CoA production.
- Modest decrease in protein levels of several electron transport chain components, while ATP synthase remained unchanged.
- Down-regulation of creatine kinase, voltage-dependent anion channel 1 (VDAC-1), HSP60, and Grp75.
- Decreased mitochondria-associated albumin and increased catalase levels.
- All observed changes were evident within 1 week of streptozotocin administration.
Conclusions:
- Diabetes induces a rapid and coordinated regulation of cardiac mitochondrial protein expression.
- The observed changes suggest a shift in substrate utilization towards fatty acids and potential alterations in energy metabolism.
- These findings highlight the early adaptive responses of heart mitochondria to diabetes.
