Transcriptional regulation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) promoter
| dc.contributor.author | Ramjiawan, Angela | |
| dc.contributor.examiningcommittee | Dixon, Ian (Physiology) Jassal, Davinder (Medicine) Mesaeli, Nasrin (Biochemistry and Medical Genetics) | en |
| dc.contributor.supervisor | Czubryt, Michael (Physiology) | en |
| dc.date.accessioned | 2010-09-10T23:04:04Z | |
| dc.date.available | 2010-09-10T23:04:04Z | |
| dc.date.issued | 2010-09-10T23:04:04Z | |
| dc.degree.discipline | Physiology | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | PGC-1α regulates cardiac mitochondrial biogenesis and energy metabolic gene expression, thus transcriptional regulation of PGC-1α gene expression is of great importance in understanding metabolic gene expression in cardiac health and disease. We provide evidence that estrogen related receptor α (ERRα, which also plays a role in cardiac energy metabolism, regulates expression of the PGC-1α gene via direct interaction with the PGC-1α gene promoter. In the presence of an inverse agonist to ERRα PGC-1α gene expression was significantly decreased, while over-expression of ERRα increased PGC-1α gene expression. We have also demonstrated that expression of PGC-1α was down regulated in hypoxic cardiomyocytes due to histone deacetylation. Our data identify ERRα as a novel regulator of cardiac PGC-1α gene expression, and suggests that promoter deacetylation in hypoxia plays a role in reduced PGC-1α expression. These results reveal a new mechanism that may contribute to energetic derangement in the heart during ischemia and/or failure. | en |
| dc.description.note | October 2010 | en |
| dc.format.extent | 682934 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | http://hdl.handle.net/1993/4160 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Cardiovascular Physiology | en |
| dc.subject | Molecular Pathophysiology | en |
| dc.title | Transcriptional regulation of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) promoter | en |
| dc.type | master thesis | en_US |