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Overexpression of phospholipid hydroperoxide glutathione peroxidase (MPHGPx) attenuates cardiac mitochondrial proteomic loss and reverses protein import detriments observed with type 1 diabetes mellitus
Author(s) -
Baseler Walter A.,
Dabkowski Erinne R.,
Jagannathan Rajaganapathi,
Thapa Dharendra,
Nichols Cody E.,
Shepherd Danielle L.,
Croston Tara L.,
Schnell David M.,
Hollander John M.
Publication year - 2012
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.26.1_supplement.1127.4
Subject(s) - diabetic cardiomyopathy , phospholipid hydroperoxide glutathione peroxidase , mitochondrion , inner mitochondrial membrane , chemistry , oxidative stress , diabetes mellitus , microbiology and biotechnology , streptozotocin , biochemistry , medicine , cardiomyopathy , biology , glutathione peroxidase , endocrinology , heart failure , superoxide dismutase
Mitochondrial dysfunction is a contributor to diabetic cardiomyopathy. Previously, we observed proteomic decrements within the mitochondrial inner membrane (IMM) and matrix of diabetic cardiac interfibrillar mitochondria (IFM) correlating with dysfunctional mitochondrial import. The goal of this study was to determine whether overexpression of MPHGPx, an antioxidant capable of scavenging membrane‐associated lipid peroxides, could preserve the mitochondrial proteome and import process. MPHGPx transgenic mice and controls were made diabetic by multiple low‐dose streptozotocin. Proteomic analyses revealed MPHGPx overexpression preserved proteins decreased within the diabetic IFM. Ingenuity Pathway Analyses indicated that OXPHOS, TCA, and FAO processes most influenced in diabetic IFM were preserved by MPHGPx overexpression. Further, IMM proteins were the most highly preserved (63%) followed by matrix proteins (34%). Mitochondrial protein import decrements were also preserved in the MPHGPx diabetic IFM (P<0.05) which correlated with increases in protein import constituents. The results indicate overexpression of MPHGPx can protect essential mitochondrial complexes in both IMM and matrix and may provide cardioprotective benefits to the diabetic heart. (Support: NIH DP2DK083095, NIH T32HL090610, AHA 10PRE3420006)