In vitro/in vivo data available
The estrogen-related receptor alpha (ERRalpha) and proliferator-activated-receptor-gamma coactivator-1alpha (PGC-1alpha) play major roles in transcriptional control of cellular energy metabolism. In particular ERRs are required for the response to various environmental challenges that require high energy levels by the organism. As central regulators of energy homeostasis, ERRs may also implicate in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome. This invention, using a lentivirus delivery system, generated HEK293T cells lines stably expressing a Luciferase reporter controlled by a sensitive estrogen response element (pGreenFire-AAB) alone or in combination with human PGC-1alpha (pCDH-510-hPGC) at the level that may reflect the physiologically acceptable state of the cell. The ERR reporter cell line detects its endogenous ERR activity using the coactivator expressing in the 293T cells, while PGC/ERR reporter cell line measures the ERR activity in the presence of its specific coregulator, PGC. The stable clonal cell lines established responded to the known antagonist, XCT790, at 10 μM level. XCT790 inhibits ERRalpha activity by disrupt its interaction with coactivator and its stability.
- Screening and identifying commercial, industrial or natural products for their effects on energy balance pathways.
- Research on endocrine function or identify endocrine disruptor chemical (e.g. the Tox21 HTS platform).
- PGC/ERR pathway plays an important role in the transcriptional control of cellular energy metabolism. It is required in response to various environmental challenges that require high energy levels by the organism. This pathway implicated in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome.