Next Article in Journal
Chemical Diversity of Codium bursa (Olivi) C. Agardh Headspace Compounds, Volatiles, Fatty Acids and Insight into Its Antifungal Activity
Next Article in Special Issue
Improving the Utility of the Tox21 Dataset by Deep Metadata Annotations and Constructing Reusable Benchmarked Chemical Reference Signatures
Previous Article in Journal
Cytotoxic Furan- and Pyrrole-Containing Scalarane Sesterterpenoids Isolated from the Sponge Scalarispongia sp.
 
Search for Articles:
Title / Keyword
Author / Affiliation
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
Journals
Molecules
Volume 24
Issue 5
10.3390/molecules24050841
molecules-logo
Submit to this Journal Review for this Journal Edit a Special Issue
► Article Menu

Article Menu

share announcement question_answer thumb_up
...
textsms
...
Article

Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays

by
Caitlin Lynch
1,
Jinghua Zhao
1,
Srilatha Sakamuru
1,
Li Zhang
1,
Ruili Huang
1,
Kristine L. Witt
2,
B. Alex Merrick
2,
Christina T. Teng
2,* and
Menghang Xia
1,*
1
National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Bethesda, MD 20814, USA
2
Division of the National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Zhihao Zhuang
Molecules 2019, 24(5), 841; https://doi.org/10.3390/molecules24050841
Received: 25 January 2019 / Revised: 19 February 2019 / Accepted: 23 February 2019 / Published: 27 February 2019
(This article belongs to the Special Issue High Throughput Screening II)
View Full-Text Download PDF
Browse Figures

Abstract

The nuclear receptor, estrogen-related receptor alpha (ERRα; NR3B1), plays a pivotal role in energy homeostasis. Its expression fluctuates with the demands of energy production in various tissues. When paired with the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the PGC/ERR pathway regulates a host of genes that participate in metabolic signaling networks and in mitochondrial oxidative respiration. Unregulated overexpression of ERRα is found in many cancer cells, implicating a role in cancer progression and other metabolism-related diseases. Using high throughput screening assays, we screened the Tox21 10K compound library in stably transfected HEK293 cells containing either the ERRα-reporter or the reporter plus PGC-1α expression plasmid. We identified two groups of antagonists that were potent inhibitors of ERRα activity and/or the PGC/ERR pathway: nine antineoplastic agents and thirteen pesticides. Results were confirmed using gene expression studies. These findings suggest a novel mechanism of action on bioenergetics for five of the nine antineoplastic drugs. Nine of the thirteen pesticides, which have not been investigated previously for ERRα disrupting activity, were classified as such. In conclusion, we demonstrated that high-throughput screening assays can be used to reveal new biological properties of therapeutic and environmental chemicals, broadening our understanding of their modes of action. View Full-Text
Keywords: ERRα; endocrine disruption; bioenergetic signaling pathways; mechanism of action; cancer ERRα; endocrine disruption; bioenergetic signaling pathways; mechanism of action; cancer
►▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

SciFeed

Share and Cite

MDPI and ACS Style

Lynch, C.; Zhao, J.; Sakamuru, S.; Zhang, L.; Huang, R.; Witt, K.L.; Merrick, B.A.; Teng, C.T.; Xia, M. Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules 2019, 24, 841. https://doi.org/10.3390/molecules24050841

AMA Style

Lynch C, Zhao J, Sakamuru S, Zhang L, Huang R, Witt KL, Merrick BA, Teng CT, Xia M. Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays. Molecules. 2019; 24(5):841. https://doi.org/10.3390/molecules24050841

Chicago/Turabian Style

Lynch, Caitlin, Jinghua Zhao, Srilatha Sakamuru, Li Zhang, Ruili Huang, Kristine L. Witt, B. A. Merrick, Christina T. Teng, and Menghang Xia. 2019. "Identification of Compounds That Inhibit Estrogen-Related Receptor Alpha Signaling Using High-Throughput Screening Assays" Molecules 24, no. 5: 841. https://doi.org/10.3390/molecules24050841

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Map by Country/Region

1
Back to TopTop