Protective effects of glycyrrhizin against β2-adrenergic receptor agonist-induced receptor internalization and cell apoptosis

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  • Shi Qian
    College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University
  • Hou Yuanyuan
    College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University
  • Yang Yang
    College of Life Sciences, Nankai University
  • Bai Gang
    College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University

書誌事項

タイトル別名
  • Protective Effects of Glycyrrhizin against .BETA.2-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis
  • Protective effects of glycyrrhizin against v 2 adrenergic receptor agonist induced receptor internalization and cell apoptosis

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It has been reported that treatment with β2 adrenergic receptor (β2AR) agonist bronchodilators may result in airway β2ARs internalization and cardiac muscle cells apoptosis. This could lead to the loss of pharmacological effect of β2AR agonists and increase adverse cardiovascular events in asthma patients receiving β2AR 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 β2AR 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 β2AR internalization. The underlying mechanisms were then identified to be that glycyrrhizin could reduce the association of β2ARs with β-arrestins and clathrin heavy chain as well as the level of G protein-coupled receptor kinase (GRK) mediated phosphorylation of β2ARs. The inhibition of receptor internalization by glycyrrhizin further lead to stabilization of the β2AR mRNA and protein expression, thus amplified the transmembrane signaling via the β2ARs. 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 β2AR agonist-induced receptor internalization and cell apoptosis. These findings might have practical implications for future strategies of combined application of glycyrrhizin with β2AR receptor agonists to improve the efficacy of bronchodilators in patients with asthma and chronic obstructive pulmonary disease (COPD).

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