Abstract
Burn-induced cardiac dysfunction is thought to involve mitochondrial dysfunction, although the mechanisms responsible are unclear. In this study, we used our established model of in vivo burn injury to understand the genetic evidence of burn-induced mitochondrial confusion dysfunction by describing cardiac mitochondrial metabolism-related gene expression after burn. Cardiac tissue was collected at 24 hours after burn injury. An O2K respirometer system was utilized to measure the cardiac mitochondrial function. Oxidative phosphorylation complex activities were determined using enzyme activity assays. RT Profiler PCR array was used to identify the differential regulation of genes involved in mitochondrial biogenesis and metabolism. The quantitative qPCR and Western blotting were applied to validate the differentially expressed genes. Burn-induced cardiac mitochondrial dysfunction was supported by the finding of decreased state 3 respiration, decreased mitochondrial electron transport chain activity in complex I, III, IV, and V, and decreased mitochondrial DNA-encoded gene expression as well as decreased levels of the corresponding proteins after burn injury. Eighty-four mitochondrial metabolism-related gene profiles were measured. The mitochondrial gene profile showed that 29 genes related to mitochondrial energy and metabolism was differentially expressed. Of these 29 genes, 16 were more than 2-fold upregulated and 13 were more than 2-fold downregulated. All genes were validated using qPCR and partial genes were correlated with their protein levels. This study provides preliminary evidence that a large percentage of mitochondrial metabolism-related genes in cardiomyocytes were significantly affected by burn injury.
Highlights
Severe burns have a significant impact on several organ systems
This study provides preliminary evidence that a large percentage of mitochondrial metabolism-related genes in cardiomyocytes were significantly affected by burn injury
Complex I activity was determined by measuring the decreased rate of NADH oxidation at 340 nm; complex II activity was determined as a decrease in absorbance at 600 nm over time; complex III activity was determined by measuring the reduction of cytochrome c at 550 nm; complex IV activity was determined by the oxidation rate of reduced cytochrome c at 550 nm; and complex V activity was determined by the rate of NADH oxidation at 340 nm
Summary
Severe burns have a significant impact on several organ systems. Cardiovascular dysfunction following a severe burn was first described in 1961 [1]. Burn-induced cardiac dysfunction manifests as tachycardia, systolic heart failure, and increased energy expenditure [1]. Mitochondrial-targeted antioxidants have been used to promote the recovery of skeletal muscle function following a burn [10]. Polymerase chain reaction (PCR)-based array and gene profiling have been used to better understand mitochondrial dysfunction in a variety of other disease processes. The PCR array was able to identify mitochondrial genes linked to the malignant transformation and disease progression [16]. We confirmed that burn-induced cardiac dysfunction was associated with changes in mitochondrial respiration, and we used PCR arrays to identify the differential expression of genes involved in mitochondrial biogenesis and metabolism in cardiomyocytes after burn
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