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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-5-2
pubmed:abstractText
It has been reported that treatment with ?? adrenergic receptor (??AR) agonist bronchodilators may result in airway ??ARs internalization and cardiac muscle cells apoptosis. This could lead to the loss of pharmacological effect of ??AR agonists and increase adverse cardiovascular events in asthma patients receiving ??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 ??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 ??AR internalization. The underlying mechanisms were then identified to be that glycyrrhizin could reduce the association of ??ARs with ?-arrestins and clathrin heavy chain as well as the level of G protein-coupled receptor kinase (GRK) mediated phosphorylation of ??ARs. The inhibition of receptor internalization by glycyrrhizin further lead to stabilization of the ??AR mRNA and protein expression, thus amplified the transmembrane signaling via the ??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 ??AR agonist-induced receptor internalization and cell apoptosis. These findings might have practical implications for future strategies of combined application of glycyrrhizin with ??AR receptor agonists to improve the efficacy of bronchodilators in patients with asthma and chronic obstructive pulmonary disease (COPD).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1347-5215
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
609-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Protective effects of glycyrrhizin against ??-adrenergic receptor agonist-induced receptor internalization and cell apoptosis.
pubmed:affiliation
College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't