Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Confusion

Version 1 : Received: 20 November 2020 / Approved: 23 November 2020 / Online: 23 November 2020 (13:59:47 CET)

A peer-reviewed article of this Preprint also exists.

Wen, J.J.; Cummins, C.B.; Williams, T.P.; Radhakrishnan, R.S. The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction. Biomedicines 2020, 8, 566. Wen, J.J.; Cummins, C.B.; Williams, T.P.; Radhakrishnan, R.S. The Genetic Evidence of Burn-Induced Cardiac Mitochondrial Metabolism Dysfunction. Biomedicines 2020, 8, 566.

Journal reference: Biomedicines 2020, 8, 566
DOI: 10.3390/biomedicines8120566

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 metabolism confusion 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 cardiac mitochondrial function. Oxidative phosphorylation complex activities were determined using enzyme activity assays. RT Profiler PCR array was used to identify differential regulation of genes involved in mitochondrial biogenesis and metabolism. Quantitative qPCR and Western Blotting were applied to validate differentially expressed genes. Burn-induced cardiac mitochondrial dysfunction was supported by the finding of decreased state 3 respiration and decreased mitochondrial electron transport chain activity in complex I, III, IV, and V following burn injury. Eighty-four mitochondrial metabolism-related gene profiles were measured. The mitochondrial gene profile showed that one third of genes related to mitochondrial energy and metabolism was differentially expressed. Of these 28 genes, 15 were more than 2-fold upregulated and 13 were more than 2-fold downregulated. All genes were validated using qPCR; 4 genes had a protein level which correlated with the observed change in gene expression. This study provides preliminary evidence that a large percentage of mitochondrial metabolism-related genes in cardiomyocytes were significantly affected by burn injury.

Keywords

burn injury; cardiac dysfunction; gene profiling; mitochondrial metabolism; oxygen consumption

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