The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction

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...

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Main Authors: Jake J. Wen, Claire B. Cummins, Taylor P. Williams, Ravi S. Radhakrishnan
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/8/12/566
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author Jake J. Wen
Claire B. Cummins
Taylor P. Williams
Ravi S. Radhakrishnan
author_facet Jake J. Wen
Claire B. Cummins
Taylor P. Williams
Ravi S. Radhakrishnan
author_sort Jake J. Wen
collection DOAJ
description 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.
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spelling doaj.art-d8f215dcf245417b8809235875b1ff102023-11-20T23:22:06ZengMDPI AGBiomedicines2227-90592020-12-0181256610.3390/biomedicines8120566The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism DysfunctionJake J. Wen0Claire B. Cummins1Taylor P. Williams2Ravi S. Radhakrishnan3Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USABurn-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.https://www.mdpi.com/2227-9059/8/12/566burn injurycardiac dysfunctiongene profilingmitochondrial metabolismoxygen consumption
spellingShingle Jake J. Wen
Claire B. Cummins
Taylor P. Williams
Ravi S. Radhakrishnan
The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
Biomedicines
burn injury
cardiac dysfunction
gene profiling
mitochondrial metabolism
oxygen consumption
title The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
title_full The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
title_fullStr The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
title_full_unstemmed The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
title_short The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction
title_sort genetic evidence of burn induced cardiac mitochondrial metabolism dysfunction
topic burn injury
cardiac dysfunction
gene profiling
mitochondrial metabolism
oxygen consumption
url https://www.mdpi.com/2227-9059/8/12/566
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