Journal article
Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling
Circulation. Heart failure, Vol.8(1), pp.188-197
01/2015
DOI: 10.1161/CIRCHEARTFAILURE.114.001540
PMCID: PMC4445759
PMID: 25504759
Abstract
Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes mellitus. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin-induced diabetic cardiomyopathy.
Exercise training promotes EcSOD expression in skeletal muscle and provides protection against diabetic cardiomyopathy; however, it is not known if enhanced expression of EcSOD in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle-specific EcSOD transgenic mice are protected from cardiac hypertrophy, fibrosis, and dysfunction under the condition of type 1 diabetes mellitus induced by streptozotocin injection. We also show that both exercise training and muscle-specific transgenic expression of EcSOD result in elevated EcSOD protein in the blood and heart without increased transcription in the heart, suggesting that enhanced expression of EcSOD from skeletal muscle redistributes to the heart. Importantly, cardiac tissue in transgenic mice displayed significantly reduced oxidative stress, aberrant cell signaling, and inflammatory cytokine expression compared with wild-type mice under the same diabetic condition.
Enhanced expression of EcSOD in skeletal muscle is sufficient to mitigate streptozotocin-induced diabetic cardiomyopathy through attenuation of oxidative stress, aberrant cell signaling, and inflammation, suggesting a cross-organ mechanism by which exercise training improves cardiac function in diabetes mellitus.
Details
- Title: Subtitle
- Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling
- Creators
- Jarrod A Call - University of VirginiaKristopher H Chain - University of VirginiaKyle S Martin - University of VirginiaVitor A Lira - University of VirginiaMitsuharu Okutsu - University of VirginiaMei Zhang - University of VirginiaZhen Yan - University of Virginia
- Resource Type
- Journal article
- Publication Details
- Circulation. Heart failure, Vol.8(1), pp.188-197
- DOI
- 10.1161/CIRCHEARTFAILURE.114.001540
- PMID
- 25504759
- PMCID
- PMC4445759
- ISSN
- 1941-3289
- eISSN
- 1941-3297
- Grant note
- T32-HL007284 / NHLBI NIH HHS R21 AR060444 / NIAMS NIH HHS R01 AR050429 / NIAMS NIH HHS AR050429 / NIAMS NIH HHS T32 HL007284 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/2015
- Academic Unit
- Health and Human Physiology
- Record Identifier
- 9984259653202771
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