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Effects of streptozotocin‐induced diabetes on the expression of cardiac mitochondrial proteins revealed by proteomic analysis
Author(s) -
Brownsey Roger William,
Kulpa Jerzy E.,
Yuen Violet,
McNeill John H.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a94-c
Subject(s) - streptozotocin , mitochondrion , citric acid cycle , ketone bodies , enzyme , diabetes mellitus , biochemistry , trypsin , metabolism , chemistry , amino acid , endocrinology , medicine , biology
Streptozotocin (STZ) induces insulin deficiency and profound changes in energy metabolism. Previous studies have addressed changes in specific enzyme activities in STZ‐diabetes. Here, we comprehensively analyze the expression of proteins in heart mitochondria using mass spectrometry. Rats were injected with a single dose of STZ (60 mg/kg) and after 12 weeks, hearts were removed and mitochondria purified by gradient centrifugation. Mitochondrial proteins were digested with trypsin and derivatized with a set of amino‐reactive iTRAQ tags. Peptides were analyzed by HPLC and tandem mass spectrometry. More than 300 mitochondrial proteins were consistently identified, based on the recognition of multiple peptide sequences. STZ diabetes led to wide‐ranging but selective changes in protein expression. Many enzymes associated with fatty acid metabolism were markedly up‐regulated in STZ diabetes. In contrast, enzymes of the citric acid cycle and the respiratory complex V were unaffected, while enzymes of amino acid and ketone metabolism, as well as components of respiratory complexes I‐IV were significantly repressed. These results reveal complex and coordinated control of multiple steps in each of several major blocks of cardiac mitochondrial metabolism during insulin deficiency. These studies were supported by grants from the Heart and Stroke Foundation and from the Canadian Institutes of Health Research.