skip to main content

Title: Development of a stable cell line with an intact PGC-1α/ERRα axis for screening environmental chemicals

Highlights: • We developed a stable cell line with intact PGC-1α/ERRα axis. • The ERRα repressor, XCT790, down regulates this pathway. • Phytoestrogen, genisten stimulates this pathway. - Abstract: The estrogen-related receptor α (ERRα) and the peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) play critical roles in the control of several physiological functions, including the regulation of genes involved in energy homeostasis. However, little is known about the ability of environmental chemicals to disrupt or modulate this important bioenergetics pathway in humans. The goal of this study was to develop a cell-based assay system with an intact PGC-1α/ERRα axis that could be used as a screening assay for detecting such chemicals. To this end, we successfully generated several stable cell lines expressing PGC-1α and showed that the reporter driven by the native ERRα hormone response unit (AAB-Luc) is active in these cell lines and that the activation is PGC-1α-dependent. Furthermore, we show that this activation can be blocked by the ERRα selective inverse agonist, XCT790. In addition, we find that genistein and bisphenol A further stimulate the reporter activity, while kaempferol has minimal effect. These cell lines will be useful for identifying environmental chemicals that modulate this important pathway.
Authors:
 [1] ; ;  [1] ; ;  [2] ;  [3]
  1. DNTP, BioMolecular Screening Branch, Division, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709 (United States)
  2. DIR, Viral Core Lab, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709 (United States)
  3. DIR Laboratory of Respiratory Biology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709 (United States)
Publication Date:
OSTI Identifier:
22416259
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 444; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CONTROL; ESTROGENS; GENES; HOMEOSTASIS; HUMAN POPULATIONS; RECEPTORS; REGULATIONS; SCREENS