Allergen-induced proteolytic cleavage of annexin-1 and activation of cytosolic phospholipase A2 in the lungs of a mouse model of asthma

Wook Chung Youn, Yeun Oh Hae, Yeong Kim Ji, Jae-Hong Kim, Ick Young Kim

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

To identify proteins that might play an important role in allergen-induced asthma, we analyzed lung extracts prepared from allergen (ovalbumin)-challenged animals in a mouse model of this condition. The combination of two-dimensional gel electrophoresis and mass spectrometry revealed that annexin-1, a 37 kDa anti-inflammatory protein that inhibits the activity of cytosolic phospholipase A2 (cPLA2), was down-regulated by allergen challenge in the lungs of ovalbumin-sensitized mice. Immunoblot analysis showed that this effect of ovalbumin challenge was attributable to proteolytic cleavage of annexin-1. The ovalbumin-induced degradation of annexin-1 was blocked by pretreatment of mice with the antioxidant N-acetylcysteine (NAC) or with sodium selenite, both of which have previously been shown to exert anti-inflammatory effects in this asthma model. Ovalbumin challenge also both increased the expression of cPLA2 in lung tissue and reduced the extent of the interaction between cPLA2 and annexin-1, and these effects were inhibited by NAC or selenite. Moreover, the concentrations of cysteinyl leukotrienes in bronchoalveolar lavage fluid and of leukotriene B4 in lung tissue were increased by ovalbumin challenge in a NAC- or selenite-sensitive manner. Together, these results suggest that allergen-induced oxidative stress results in proteolysis of annexin-1 and consequent up-regulation of cPLA2 activity and leukotriene production in this mouse model of asthma, and that the anti-inflammatory effects of selenite may provide a basis for the development of new antiasthmatic drugs.

Original languageEnglish
Pages (from-to)3328-3334
Number of pages7
JournalProteomics
Volume4
Issue number11
DOIs
Publication statusPublished - 2004 Nov 1

Fingerprint

Cytosolic Phospholipases A2
Annexins
Ovalbumin
Allergens
Asthma
Chemical activation
Selenious Acid
Lung
Acetylcysteine
Anti-Inflammatory Agents
Tissue
Proteolysis
Anti-Asthmatic Agents
Sodium Selenite
Oxidative stress
Leukotriene B4
Leukotrienes
Electrophoresis, Gel, Two-Dimensional
Bronchoalveolar Lavage Fluid
Electrophoresis

Keywords

  • Annexin-1
  • Asthma
  • Cytosolic phospholipase A
  • Matrix-assisted laser desorption/ionization-time of flight
  • Two-dimensional gel electrophoresis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Allergen-induced proteolytic cleavage of annexin-1 and activation of cytosolic phospholipase A2 in the lungs of a mouse model of asthma. / Youn, Wook Chung; Hae, Yeun Oh; Ji, Yeong Kim; Kim, Jae-Hong; Kim, Ick Young.

In: Proteomics, Vol. 4, No. 11, 01.11.2004, p. 3328-3334.

Research output: Contribution to journalArticle

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abstract = "To identify proteins that might play an important role in allergen-induced asthma, we analyzed lung extracts prepared from allergen (ovalbumin)-challenged animals in a mouse model of this condition. The combination of two-dimensional gel electrophoresis and mass spectrometry revealed that annexin-1, a 37 kDa anti-inflammatory protein that inhibits the activity of cytosolic phospholipase A2 (cPLA2), was down-regulated by allergen challenge in the lungs of ovalbumin-sensitized mice. Immunoblot analysis showed that this effect of ovalbumin challenge was attributable to proteolytic cleavage of annexin-1. The ovalbumin-induced degradation of annexin-1 was blocked by pretreatment of mice with the antioxidant N-acetylcysteine (NAC) or with sodium selenite, both of which have previously been shown to exert anti-inflammatory effects in this asthma model. Ovalbumin challenge also both increased the expression of cPLA2 in lung tissue and reduced the extent of the interaction between cPLA2 and annexin-1, and these effects were inhibited by NAC or selenite. Moreover, the concentrations of cysteinyl leukotrienes in bronchoalveolar lavage fluid and of leukotriene B4 in lung tissue were increased by ovalbumin challenge in a NAC- or selenite-sensitive manner. Together, these results suggest that allergen-induced oxidative stress results in proteolysis of annexin-1 and consequent up-regulation of cPLA2 activity and leukotriene production in this mouse model of asthma, and that the anti-inflammatory effects of selenite may provide a basis for the development of new antiasthmatic drugs.",
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