An in vivo system for the identification of ligands for peroxisome proliferatoractivated receptors
Year: 2015
Type: dissertation
Abstract: Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptors (NRs) that play major roles in metabolism and development and, when disrupted, lead to disorders such as cancer, diabetes and obesity. Our laboratory has established a transgenic Ligand Trap system in zebrafish for high throughput screening of drugs to identify novel activators of human NRs. We have identified Coenzyme Q10 (CoQ10) as an activator of PPAR-gamma in a presumed tissue specific manner. To demonstrate that CoQ10 directly binds to PPARs, we expressed PPARs in bacteria and zebrafish embryos and treated with CoQ10. Ligand-bound receptors were purified and analyzed by denaturing mass spectrometry. Data suggest that CoQ10 binds to PPAR-alpha and PPAR-gamma, but not to PPAR-beta. Future experiments will focus to confirm direct binding to PPAR subtypes. Once verified, subsequent studies will explore the significance of CoQ10 as a PPAR ligand in the context of transcription machinery complex formation.
Source: TSpace (University of Toronto)
Author: Richard Heungki Lee
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2561776412