Rapid Screening of Glucocorticoid Receptor (GR) Effectors Using Cortisol-Detecting Sensor Cells
| Autor: | Soyoun Kim, Chungwon Kang, Minhyeong Lee, Euiyeon Lee, Seungil Park, Youngeun Kwon, Jeahee Ryu, Dae Yeon Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Hydrocortisone Cell Drug Evaluation Preclinical Biosensing Techniques Pharmacology 01 natural sciences Dexamethasone Myoblasts Glucocorticoid receptor Fluorometry Biology (General) Spectroscopy Estradiol Molecular Structure Effector Chemistry Mentha piperita General Medicine Computer Science Applications Menthol Mifepristone Protein Transport medicine.anatomical_structure Agonist Signal peptide QH301-705.5 medicine.drug_class Recombinant Fusion Proteins selective GR agonist Fluorescence Polarization cortisol signal peptide reconstitution Catalysis Article Proinflammatory cytokine Inteins Inorganic Chemistry 03 medical and health sciences Receptors Glucocorticoid cell-based sensor Protein splicing medicine Oils Volatile Humans Plant Oils Protein Splicing Physical and Theoretical Chemistry Cyproterone Acetate Muscle Skeletal QD1-999 Molecular Biology conditional protein splicing Organic Chemistry glucocorticoid receptor (GR) 0104 chemical sciences 010404 medicinal & biomolecular chemistry Luminescent Proteins 030104 developmental biology GR effector Atrophy Intein Limonene HeLa Cells |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 9 International Journal of Molecular Sciences, Vol 22, Iss 4747, p 4747 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22094747 |
| Popis: | Cortisol, a stress hormone, plays key roles in mediating stress and anti-inflammatory responses. As abnormal cortisol levels can induce various adverse effects, screening cortisol and cortisol analogues is important for monitoring stress levels and for identifying drug candidates. A novel cell-based sensing system was adopted for rapid screening of cortisol and its functional analogues under complex cellular regulation. We used glucocorticoid receptor (GR) fused to a split intein which reconstituted with the counterpart to trigger conditional protein splicing (CPS) in the presence of targets. CPS generates functional signal peptides which promptly translocate the fluorescent cargo. The sensor cells exhibited exceptional performance in discriminating between the functional and structural analogues of cortisol with improved sensitivity. Essential oil extracts with stress relief activity were screened using the sensor cells to identify GR effectors. The sensor cells responded to peppermint oil, and L-limonene and L-menthol were identified as potential GR effectors from the major components of peppermint oil. Further analysis indicated L-limonene as a selective GR agonist (SEGRA) which is a potential anti-inflammatory agent as it attenuates proinflammatory responses without causing notable adverse effects of GR agonists. |
| Databáze: | OpenAIRE |
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