A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program
Copyright policy )A role for Sp and nuclear receptor transcription factors in a cardiac hypertrophic growth program
During cardiac hypertrophy, the chief myocardial energy source switches from fatty acid β-oxidation (FAO) to glycolysis—a reversion to fetal metabolism. The expression of genes encoding myocardial FAO enzymes was delineated in a murine ventricular pressure overload preparation to characterize the molecular regulatory events involved in the alteration of energy substrate utilization during cardiac hypertrophy. Expression of genes involved in the thioesterification, mitochondrial import, and β-oxidation of fatty acids was coordinately down-regulated after 7 days of right ventricular (RV) pressure overload. Results of RV pressure overload studies in mice transgenic for the promoter region of the gene encoding human medium-chain acyl-CoA dehydrogenase (MCAD, which catalyzes a rate-limiting step in the FAO cycle) fused to a chloramphenicol acetyltransferase reporter confirmed that repression of MCAD gene expression in the hypertrophied ventricle occurred at the transcriptional level. Electrophoretic mobility-shift assays performed with MCAD promoter fragments and nuclear protein extracts prepared from hypertrophied and control RV identified pressure overload-induced protein/DNA interactions at a regulatory unit shown previously to confer control of MCAD gene transcription during cardiac development. Antibody “supershift” studies demonstrated that members of the Sp (Sp1, Sp3) and nuclear hormone receptor [chicken ovalbumin upstream promoter transcription factor (COUP-TF)/erbA-related protein 3] families interact with the pressure overload-responsive unit. Cardiomyocyte transfection studies confirmed that COUP-TF repressed the transcriptional activity of the MCAD promoter. The DNA binding activities and nuclear expression of Sp1/3 and COUP-TF in normal fetal mouse heart were similar to those in the hypertrophied adult heart. These results identify a transcriptional regulatory mechanism involved in the reinduction of a fetal metabolic program during pressure overload-induced cardiac hypertrophy.
- University of California, San Diego United States
- University of Mary United States
- Washington University in St. Louis United States
Chloramphenicol O-Acetyltransferase, Binding Sites, Base Sequence, Myocardium, Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear, Cardiomegaly, Mice, Inbred Strains, Mice, Transgenic, Acyl-CoA Dehydrogenase, Gene Expression Regulation, Enzymologic, Mice, Inbred C57BL, Mice, Acyl-CoA Dehydrogenases, Animals, Newborn, Oligodeoxyribonucleotides, Animals, Humans, Glycolysis, Cells, Cultured
Chloramphenicol O-Acetyltransferase, Binding Sites, Base Sequence, Myocardium, Molecular Sequence Data, Receptors, Cytoplasmic and Nuclear, Cardiomegaly, Mice, Inbred Strains, Mice, Transgenic, Acyl-CoA Dehydrogenase, Gene Expression Regulation, Enzymologic, Mice, Inbred C57BL, Mice, Acyl-CoA Dehydrogenases, Animals, Newborn, Oligodeoxyribonucleotides, Animals, Humans, Glycolysis, Cells, Cultured
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).197 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 1% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!