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J Thorac Dis. 2013 Dec;5(6):797-805. doi: 10.3978/j.issn.2072-1439.2013.12.42.

Identification of proteasome subunit beta type 3 involved in the potential mechanism of corticosteroid protective effectiveness on beta-2 adrenoceptor desensitization by a proteomics approach.

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  • 1Department of Respiratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China.

Abstract

BACKGROUND:

Asthma is a chronic inflammatory disease characterized by airway inflammation with mucus hypersecretion and hyperresponsiveness to various nonspecific stimuli. Corticosteroids are usually used to prevent β2 adrenoceptor (β2AR) desensitization in clinical and experimental practice. But the exact mechanism of corticosteroid effectiveness on β2AR desensitization is unclear.

OBJECTIVES:

To find the potential mechanisms related to the protective effects of corticosteroid on salbutamol induced β2AR desensitization by a proteomics approach.

METHODS:

Thirty-two BALB/c (6-8 weeks old) mice were divided into four groups: group A, control group, phosphate buffered saline (PBS)-treated group; group B, asthmatic group, treated by ovalbumin (OVA); group C, β2AR desensitized asthmatic group, treated by OVA and salbutamol (SBT) and group D, corticosteroid-treated β2AR desensitized asthmatic group, treated with OVA, SBT and Dexamethasone (DEX). After administrated with those drugs, their serum total IgE, bronchoalveolar lavage fluid (BALF) cytokine concentration, airway resistance and membrane receptor number of β2AR were evaluated. After then, the mice of group C and D were sacrificed, their protein from lung tissue were extracted and then seperated by two-dimensional gel electrophoresis (2DE). Then, the isolated protein spots were analyzed by ImageMaster software and mass spectrometry. Bioinformatic tools were used to search these protein spots and find interesting protein spots associated with corticosteroid protective effect on β2AR desensitization. Finally, these protein spots were confirmed by Western blotting.

RESULTS:

With inflammatory cell count, cytokine concentration of BALF, pathological sections, total serum IgE, airway resistance, membrane receptor number and β2AR total amount changes, asthmatic mouse model and β2AR desensitization asthmatic mouse model were successfully established. Seventeen protein spots were found different expression between group C and group D, 4 protein spots were down-regulated and 13 protein spots were up-regulated compared to group C. Proteasome subunit beta type 3 was down-regulated.

CONCLUSIONS:

Increased proteasome subunit beta type 3 expression may be responsible for salbutamol-induced β2AR desensitization in asthmatic disease, and DEX possibly render the β2AR resensitization partially by decreasing the content of proteasome.

KEYWORDS:

corticosteroid; electrophoresis; mass spectrometry; proteasome; proteomics; β2 adrenoceptor (β2AR)

PMID:
24409358
[PubMed]
PMCID:
PMC3886689
Free PMC Article
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