NDLI: Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

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Year: 2008, Volume: 40, Issue: 2

Year: 2008, Volume: 40, Issue: 1

Year: 2007, Volume: 39

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Angiopoietin-1 variant, COMP-Ang1 attenuates hydrogen peroxide-induced acute lung injury

Content Provider	PubMed Central
Author	Kim, So Ri Lee, Kyung Sun Park, Seoung Ju Min, Kyung Hoon Lee, Ka Young Choe, Yeong Hun Hong, Sang Hyun Koh, Gou Young Lee, Yong Chul
Copyright Year	2008
Abstract	Reactive oxygen species (ROS) play a crucial role in acute lung injury. Tissue inflammation, the increased vascular permeability, and plasma exudation are cardinal features of acute lung injury. Angiopoietin-1 (Ang1) has potential therapeutic applications in preventing vascular leakage and also has beneficial effects in several inflammatory disorders. Recently developed COMP-Ang1 is more potent than native Ang1 in phosphorylating tyrosine kinase with immunoglobulin and EGF homology domain 2 receptor in endothelial cells. However, there are no data on effects and related molecular mechanisms of COMP-Ang1 on ROS-induced acute lung injury. We used hydrogen peroxide (H2O2)-inhaled mice to evaluate the effect of COMP-Ang1 on pulmonary inflammation, bronchial hyper-responsiveness, and vascular leakage in acute lung injury. The results have revealed that VEGF expression, the levels of IL-4, TNF-α, IL-1β, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in lungs, the levels of hypoxia-inducible factor-1α (HIF-1α) and NF-κB in nuclear protein extracts, phosphorylation of Akt, and vascular permeability were increased after inhalation of H2O2 and that the administration of COMP-Ang1 markedly reduced airway hyper-responsiveness, pulmonary inflammation, plasma extravasation, and the increases of cytokines, adhesion molecules, and VEGF in lungs treated with H2O2. We have also found that the activation of HIF-1α and NF-κB and the increase of phosphoinositide 3-kinase activity in lung tissues after H2O2 inhalation were decreased by the administration of COMP-Ang1. These results suggest that COMP-Ang1 ameliorates ROS-induced acute lung injury through attenuating vascular leakage and modulating inflammatory mediators.
Related Links	http://dx.doi.org/10.3858/emm.2008.40.3.320
Starting Page	320
File Format	PDF
ISSN	12263613
Journal	Experimental & Molecular Medicine
Issue Number	3
Volume Number	40
Language	English
Publisher	Korean Society of Medical Biochemistry and Molecular Biology
Publisher Date	2008-01-01
Access Restriction	Open
Rights Holder	Korean Society of Medical Biochemistry and Molecular Biology
Subject Keyword	Clinical Biochemistry Molecular Medicine Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Molecular Biology Clinical Biochemistry Molecular Medicine

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