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Mitochondrial Overexpression of Phospholipid Hydroperoxide Glutathione Peroxidase 4 (mPHGPx) Provides Cardioprotection From Type 1 Diabetes Mellitus Insult
Author(s) -
Dabkowski Erinne R,
Baseler Walt A,
Croston Tara L,
Williamson Courtney L,
Hollander John M
Publication year - 2010
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.24.1_supplement.789.2
Subject(s) - cardioprotection , medicine , mitochondrion , streptozotocin , diabetes mellitus , endocrinology , diabetic cardiomyopathy , glutathione peroxidase , type 2 diabetes mellitus , lipid peroxidation , genetically modified mouse , type 2 diabetes , chemistry , ischemia , transgene , oxidative stress , biochemistry , heart failure , superoxide dismutase , cardiomyopathy , gene
Evidence suggests that the inner mitochondria membrane (IMM) is a target for the deleterious effects of type 1 diabetes mellitus (DM). Maintenance of IMM integrity represents a specific locus for testing directed prophylactic intervention. We previously reported that type 1 DM imparts differential effects on spatially distinct mitochondrial subpopulations, subsarcolemmal (SSM) and interfibrillar (IFM). The goal of this study was to determine whether overexpression of a mitochondrially‐targeted antioxidant enzyme, mPHGPx, could elicit protection to mitochondria during type 1 DM. MPHGPx transgenic mice and littermate controls were made diabetic through low dose injections of streptozotocin. Five weeks post hyperglycemia onset, ejection fraction and fractional shortening were decreased in the diabetic heart (*P<0.05), and were reversed with mPHGPx overexpression (*P<0.05). MPHGPx overexpression in the diabetic heart was associated with increased electron transport chain complex activities in IFM as compared to diabetic controls (*P<0.05), with no differences on SSM. Hydrogen peroxide and lipid peroxidation were attenuated in the mPHGPx diabetic IFM as compared to diabetic controls (*P<0.05), with no changes in the SSM. These results indicate that mPHGPx overexpression provides cardioprotection to the diabetic heart, which is associated with mitochondrial subpopulation‐specific protection.