GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea
Abstract
1 Scope: The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood.2 Methods and results: We found that GPRC6A, a multi-ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex hormone production, and prostate cancer progression, is a target for gallates. Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG) dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not in non-transfected controls. SG also stimulated insulin secretion in β-cells isolated from wild-type mice similar to the endogenous GPRC6A ligands, osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG resulted in loss of GPRC6A agonist activity. Another component of green tea, epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in stimulating glucose production in CH10T1/2 cells. Using structural models of the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to bind to sites in both the VFT and 7-TM.3 In conclusion, GA and EGCG have offsetting agonist and antagonist effects on GPRC6A that may account for the variable metabolic effectmore »
- Authors:
-
- Univ. of Tennessee Health Science Center, Memphis, TN (United States). Dept. of Medicine
- Univ. of Tennessee, Knoxville, TN (United States). UT/ORNL Center for Molecular Biophysics
- Univ. of Tennessee, Knoxville, TN (United States). UT/ORNL Center for Molecular Biophysics and Dept. of Biochemistry and Cellular and Molecular Biology
- Publication Date:
- Research Org.:
- Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1459287
- Grant/Contract Number:
- AC05-00OR22725
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Molecular Nutrition & Food Research
- Additional Journal Information:
- Journal Volume: 62; Journal Issue: 8; Journal ID: ISSN 1613-4125
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; computational modeling; EGCG; gallic acid; GPCR; GPRC6A
Citation Formats
Pi, Min, Kapoor, Karan, Ye, Ruisong, Smith, Jeremy C., Baudry, Jerome, and Quarles, Leigh D. GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea. United States: N. p., 2018.
Web. doi:10.1002/mnfr.201700770.
Pi, Min, Kapoor, Karan, Ye, Ruisong, Smith, Jeremy C., Baudry, Jerome, & Quarles, Leigh D. GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea. United States. https://doi.org/10.1002/mnfr.201700770
Pi, Min, Kapoor, Karan, Ye, Ruisong, Smith, Jeremy C., Baudry, Jerome, and Quarles, Leigh D. Wed .
"GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea". United States. https://doi.org/10.1002/mnfr.201700770. https://www.osti.gov/servlets/purl/1459287.
@article{osti_1459287,
title = {GPCR6A Is a Molecular Target for the Natural Products Gallate and EGCG in Green Tea},
author = {Pi, Min and Kapoor, Karan and Ye, Ruisong and Smith, Jeremy C. and Baudry, Jerome and Quarles, Leigh D.},
abstractNote = {1 Scope: The molecular mechanisms whereby gallates in green tea exert metabolic effects are poorly understood.2 Methods and results: We found that GPRC6A, a multi-ligand-sensing G-protein-coupled receptor that regulates energy metabolism, sex hormone production, and prostate cancer progression, is a target for gallates. Sodium gallate (SG), gallic acid (GA) > ethyl gallate (EG) > octyl gallate (OG) dose dependently activated ERK in HEK-293 cells transfected with GPRC6A but not in non-transfected controls. SG also stimulated insulin secretion in β-cells isolated from wild-type mice similar to the endogenous GPRC6A ligands, osteocalcin (Ocn) and testosterone (T). Side-chain additions to create OG resulted in loss of GPRC6A agonist activity. Another component of green tea, epigallocatechin 3-gallate (EGCG), dose-dependently inhibited Ocn activation of GPRC6A in HEK-293 cells transfected with GPRC6A and blocked the effect of Ocn in stimulating glucose production in CH10T1/2 cells. Using structural models of the venus fly trap (VFT) and 7-transmembrane (7-TM) domains of GPRC6A, calculations suggest that l-amino acids and GA bind to the VFT, whereas EGCG is calculated to bind to sites in both the VFT and 7-TM.3 In conclusion, GA and EGCG have offsetting agonist and antagonist effects on GPRC6A that may account for the variable metabolic effect of green tea consumption.},
doi = {10.1002/mnfr.201700770},
journal = {Molecular Nutrition & Food Research},
number = 8,
volume = 62,
place = {United States},
year = {Wed Feb 21 00:00:00 EST 2018},
month = {Wed Feb 21 00:00:00 EST 2018}
}
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