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Characterization of proteomic changes in cardiac mitochondria in streptozotocin‐diabetic rats using iTRAQ™ isobaric tags
Author(s) -
Jüllig Mia,
Hickey Anthony J.,
Middleditch Martin J.,
Crossman David J.,
Lee Stanley C.,
Cooper Garth J. S.
Publication year - 2007
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.200600831
Subject(s) - isobaric process , streptozotocin , mitochondrion , diabetic cardiomyopathy , chemistry , diabetes mellitus , pharmacology , medicine , biochemistry , endocrinology , heart failure , physics , cardiomyopathy , thermodynamics
Diabetes now affects more than 5% of the world's population and heart failure is the most common cause of death amongst diabetic patients. Accumulating evidence supports a view that myocardial mitochondrial structural and functional changes are central to the onset of diabetic heart failure, but the exact nature of these changes at the proteomic level remains unclear.Here we report on proteomic changes in diabetic rat heart mitochondria following 120 days of streptozotocin‐diabetes using the recently developed iTRAQ™ labeling method, which permits quantification of proteins directly from complex mixtures, bypassing the limitations associated with gel‐based methods such as 2‐DE. Of 252 unique proteins identified, 144 were represented in at least three of six individual paired experiments. Relative amounts of 65 proteins differed significantly between the groups, confirming that the cardiac mitochondrial proteome is indeed impacted by diabetes. The most significant changes were increased protein levels of enzymes involved in mitochondrial oxidation of long‐chain fatty acids, which was also confirmed by enzyme assays, and decreased levels of multiple enzymes involved in oxidative phosphorylation and catabolism of short‐chain fatty acids and branched‐chain amino acids. We also found significant changes in levels of several enzymes linked to oxidative stress.