Journal article
Protective Effects of Glycyrrhizin against beta(2)-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis
Biological & pharmaceutical bulletin, Vol.34(5), pp.609-617
05/01/2011
DOI: 10.1248/bpb.34.609
PMID: 21532146
Abstract
It has been reported that treatment with A adrenergic receptor (beta(2)AR) agonist bronchodilators may result in airway beta(2)ARs internalization and cardiac muscle cells apoptosis. This could lead to the loss of pharmacological effect of beta(2)AR agonists and increase adverse cardiovascular events in asthma patients receiving beta(2)AR agonist therapy. Glycyrrhizin, the major bioactive component of licorice root extract, has been reported to exhibit protective effect on respiratory system. Here, we investigate the effects of glycyrrhizin against beta(2)AR agonist salbutamol-induced receptor internalization and cell apoptosis. In our study, the live cell confocal imaging and fixed-cell enzyme-linked immunosorbent assay (ELISA) assay revealed that glycyrrhizin significantly inhibited salbutamol-induced surface beta(2)AR internalization. The underlying mechanisms were then identified to be that glycyrrhizin could reduce the association of beta(2)ARs with beta-arrestins and clathrin heavy chain as well as the level of G protein-coupled receptor kinase (GRK) mediated phosphorylation of beta(2)ARs. The inhibition of receptor internalization by glycyrrhizin further lead to stabilization of the beta(2)AR mRNA and protein expression, thus amplified the transmembrane signaling via the beta(2)ARs. We also proved that glycyrrhizin could profoundly attenuate salbutamol-induced early cellular apoptosis by regulating the expressions of B-cell lymphoma 2 (Bcl-2) family genes. Taken together, our results suggest that glycyrrhizin exhibits protective effects against beta(2)AR agonist-induced receptor internalization and cell apoptosis. These findings might have practical implications for future strategies of combined application of glycyrrhizin with beta(2)AR receptor agonists to improve the efficacy of bronchodilators in patients with asthma and chronic obstructive pulmonary disease (COPD).
Details
- Title: Subtitle
- Protective Effects of Glycyrrhizin against beta(2)-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis
- Creators
- Qian Shi - Nankai UniversityYuanyuan Hou - Nankai UniversityYang Yang - Nankai UniversityGang Bai - Nankai University
- Resource Type
- Journal article
- Publication Details
- Biological & pharmaceutical bulletin, Vol.34(5), pp.609-617
- Publisher
- Pharmaceutical Soc Japan
- DOI
- 10.1248/bpb.34.609
- PMID
- 21532146
- ISSN
- 0918-6158
- eISSN
- 1347-5215
- Number of pages
- 9
- Grant note
- 81001682 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 05/01/2011
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984363290702771
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