%0 Journal Article
%T Increased expression of estrogen-related receptor ¦Â during adaptation of adult cardiomyocytes to sustained hypoxia
%A Craig C Beeson
%A Gyda C Beeson
%A Kathryn F Cunningham
%A Paul J McDermott
%J Archive of "American Journal of Cardiovascular Disease".
%D 2016
%X Estrogen-related Receptors (ERR) are members of the steroid hormone receptor superfamily of transcription factors that regulate expression of genes required for energy metabolism including mitochondrial biogenesis, fatty acid oxidation and oxidative phosphorylation. While ERR¦Á and EPP¦Ã isoforms are known to share a wide array of target genes in the adult myocardium, the function of ERR¦Â has not been characterized in cardiomyocytes. The purpose of this study was to determine the role of ERR¦Â in regulating energy metabolism in adult cardiomyocytes in primary culture. Adult feline cardiomyocytes were electrically stimulated to contract in either hypoxia (0.5% O2) or normoxia (21% O2). As compared to baseline values measured in normoxia, ERR¦Â mRNA levels increased significantly after 8 hours of hypoxia and remained elevated over 24 h. Conversely, ERR¦Â mRNA decreased to normoxic levels after 4 hours of reoxygenation. Hypoxia increased expression of the ¦Á and ¦Â isoforms of Peroxisome Proliferator-Activated Receptor ¦Ã Coactivator-1 (PGC-1) mRNA by 6-fold and 3-fold, respectively. Knockdown of ERR¦Â expression via adenoviral-mediated delivery of ERR¦Â shRNA blocked hypoxia-induced increases in PGC-1¦Â mRNA, but not PGC-1¦Á mRNA. Loss of ERR¦Â had no effect on mtDNA content as measured after 24 h of hypoxia. To determine whether loss of ERR¦Â affected mitochondrial function, oxygen consumption rates (OCR) were measured in contracting versus quiescent cardiomyocytes in normoxia. OCR was significantly lower in contracting cardiomyocytes expressing ERR¦Â shRNA than scrambled shRNA controls. Maximal OCR also was reduced by ERR¦Â knockdown. In conclusion: 1) hypoxia increases in ERR¦Â mRNA expression in contracting cardiomyocytes; 2) ERR¦Â is required for induction of the PGC-1¦Â isoform in response to hypoxia; 3) ERR¦Â expression is required to sustain OCR in normoxic conditions
%K Cardiomyocyte
%K hypoxia
%K estrogen-related receptor
%K estrogen-related receptor ¦Â
%K peroxisome proliferator-activated receptor ¦Ã coactivator-1
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4913214/