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Mitochondrial phospholipid hydroperoxide glutathione peroxidase (mPHGPx) overexpression preserves the inner mitochondrial membrane in the diabetic heart
Author(s) -
Dabkowski Erinne,
Baseler Walter,
Croston Tara,
Thapa Dharendra,
Hollander John
Publication year - 2011
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.25.1_supplement.1095.5
Subject(s) - cardiolipin , mitochondrion , phospholipid hydroperoxide glutathione peroxidase , diabetic cardiomyopathy , phospholipid , inner mitochondrial membrane , diabetes mellitus , proteome , streptozotocin , medicine , oxidative stress , endocrinology , chemistry , microbiology and biotechnology , glutathione peroxidase , biology , biochemistry , heart failure , membrane , cardiomyopathy , superoxide dismutase
Mitochondrial dysfunction contributes to cardiac abnormalities in the diabetic heart. The inner mitochondria membrane (IMM) is susceptible to damage associated with diabetes mellitus. Previously, we observed diminished IMM protein content and function in the diabetic heart. Cardiolipin, an essential IMM phospholipid, was also decreased. Thus, therapeutic interventions aimed at preserving the IMM phospholipids and proteins may be beneficial. The goal of this study was to determine whether overexpression of mPHGPx preserves mitochondrial proteomes and cardiolipin content in the diabetic heart. MPHGPx overexpressing mice and controls were made diabetic through streptozotocin injection. Five weeks post hyperglycemia onset, cardiac mitochondrial subpopulations were isolated and proteomes were assessed. Proteomic analyses revealed that 29 proteins decreased in the diabetic interfibrillar mitochondria compared to control were preserved with overexpression of MPHGPx. Most proteins were part of the electron transport chain with 6/14 from complex I, 2/14 from complex IV, and 4/14 from complex V. Further, cardiolipin content was preserved with overexpression of mPHGPx. These results indicate that overexpression of antioxidants aimed at preserving the IMM, such as mPHGPx, may provide cardioprotective benefits to the diabetic heart. (Supported by NIH DP2DK083095, AHA 0855484D, AHA 0815406D)