Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling.
Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling.
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DOI：
10.1161/circheartfailure.114.001540
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Yan Z
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文献类型：
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作者：
Call JA;Chain KH;Martin KS;Lira VA;Okutsu M;Zhang M;Yan Z
运动训练增强骨骼肌细胞外超氧化物歧化酶（EcSOD）的表达，改善糖尿病患者的健康状况。本研究的目的是确定骨骼肌EcSOD表达的增强是否足以减轻链脲佐菌素（STZ）诱导的糖尿病心肌病（DCM）。运动训练促进骨骼肌中EcSOD的表达，并提供针对DCM的保护;然而，尚不清楚骨骼肌中增强的EcSOD表达是否在这种保护中起功能性作用。在这里，我们表明，骨骼肌特异性EcSOD转基因小鼠（TG）的保护下，STZ注射诱导的1型糖尿病的条件下，心肌肥厚，纤维化和功能障碍。我们还表明，运动训练和肌肉特异性转基因表达的EcSOD的结果在升高的EcSOD蛋白在血液和心脏中没有增加在心脏中的转录，这表明增强表达的EcSOD从骨骼肌重新分配到心脏。重要的是，在相同的糖尿病条件下，与野生型小鼠相比，TG小鼠的心脏组织显示出显著降低的氧化应激、异常细胞信号传导和炎性细胞因子表达。骨骼肌中EcSOD表达的增强足以通过减轻氧化应激、异常细胞信号传导和炎症来减轻STZ诱导的DCM，这表明运动训练改善糖尿病心脏功能的跨器官机制。
Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM). Exercise training promotes EcSOD expression in skeletal muscle and provides protection against DCM; however, it is not known if enhanced EcSOD expression in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle-specific EcSOD transgenic mice (TG) are protected from cardiac hypertrophy, fibrosis and dysfunction under the condition of type-1 diabetes induced by STZ 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 enhanced expression of EcSOD from skeletal muscle redistributes to the heart. Importantly, cardiac tissue in TG 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 STZ-induced DCM through attenuation of oxidative stress, aberrant cell signaling and inflammation, suggesting a cross-organ mechanism by which exercise training improves cardiac function in diabetes.