Journal article
High-Throughput GPCRome Screen of Pollutants Reveals the Activity of Polychlorinated Biphenyls at Melatonin and Sphingosine-1-phosphate Receptors
Chemical research in toxicology, Vol.37(2), pp.439-449
02/19/2024
DOI: 10.1021/acs.chemrestox.3c00388
PMCID: PMC10880096
PMID: 38295294
Appears in UI Libraries Support Open Access
Abstract
Exposure to environmental pollutants is linked to numerous toxic outcomes, warranting concern about the effect of pollutants on human health. To assess the threat of pollutant exposure, it is essential to understand their biological activity. Unfortunately, gaps remain for many pollutants' specific biological activity and molecular targets. A superfamily of signaling proteins, G-protein-coupled receptors (GPCRs), has been shown as potential targets for pollutant activity. However, research investigating the pollutant activity at the GPCRome is scarce. This work explores pollutant activity across a library of human GPCRs by leveraging modern high-throughput screening techniques devised for drug discovery and pharmacology. We designed and implemented a pilot screen of eight pollutants at 314 human GPCRs and discovered specific polychlorinated biphenyl (PCB) activity at sphingosine-1-phosphate and melatonin receptors. The method utilizes open-source resources available to academic and governmental institutions to enable future campaigns that screen large numbers of pollutants. Thus, we present a novel high-throughput approach to assess the biological activity and specific targets of pollutants.
Details
- Title: Subtitle
- High-Throughput GPCRome Screen of Pollutants Reveals the Activity of Polychlorinated Biphenyls at Melatonin and Sphingosine-1-phosphate Receptors
- Creators
- Joshua C Wilkinson - University of IowaHans-Joachim Lehmler - Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa 52242, United StatesDavid L Roman - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.37(2), pp.439-449
- DOI
- 10.1021/acs.chemrestox.3c00388
- PMID
- 38295294
- PMCID
- PMC10880096
- NLM abbreviation
- Chem Res Toxicol
- eISSN
- 1520-5010
- Publisher
- American Chemical Society
- Grant note
- DOI: 10.13039/100000066, name: National Institute of Environmental Health Sciences, award: NIH P30 ES005605; DOI: 10.13039/100008893, name: University of Iowa
- Language
- English
- Electronic publication date
- 01/31/2024
- Date published
- 02/19/2024
- Academic Unit
- Pharmacy; Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984555558502771
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