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Molecular Pharmacology

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Research ArticleArticle

A Prodrug of Cysteine, l-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma

Kyung Sun Lee, Hee Sun Park, Seoung Ju Park, So Ri Kim, Kyung Hoon Min, Sun Mi Jin, Kwang-Hyun Park, Uh-Hyun Kim, Chan Young Kim and Yong Chul Lee
Molecular Pharmacology November 2005, 68 (5) 1281-1290; DOI: https://doi.org/10.1124/mol.105.016055
Kyung Sun Lee
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Hee Sun Park
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Seoung Ju Park
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So Ri Kim
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Kyung Hoon Min
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Sun Mi Jin
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Kwang-Hyun Park
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Uh-Hyun Kim
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Chan Young Kim
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Yong Chul Lee
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Abstract

Inflammation of the asthmatic airway is usually accompanied by increased vascular permeability and plasma exudation. Oxidative stress plays critical roles in airway inflammation. Although reactive oxygen species (ROS) are shown to cause vascular leakage, the mechanisms by which ROS induce increased vascular permeability are not clearly understood. We have used a murine model of asthma to evaluate the effect of l-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine that acts as an antioxidant, more specifically in the increase of vascular permeability. These mice develop the following typical pathophysiological features of asthma in the lungs: increased numbers of inflammatory cells of the airways, airway hyper-responsiveness, increased vascular permeability, and increased levels of vascular endothelial growth factor (VEGF). Administration of OTC markedly reduced plasma extravasation and VEGF levels in allergen-induced asthmatic lungs. We also showed that at 72 h after ovalbumin inhalation, increased levels of hypoxia-inducible factor-1α (a transcriptional activator of VEGF) in nuclear protein extracts of lung tissues were decreased by the administration of OTC. These results indicate that OTC modulates vascular permeability by lowering VEGF expression.

  • Received June 22, 2005.
  • Accepted August 12, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 68 (5)
Molecular Pharmacology
Vol. 68, Issue 5
1 Nov 2005
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Research ArticleArticle

A Prodrug of Cysteine, l-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma

Kyung Sun Lee, Hee Sun Park, Seoung Ju Park, So Ri Kim, Kyung Hoon Min, Sun Mi Jin, Kwang-Hyun Park, Uh-Hyun Kim, Chan Young Kim and Yong Chul Lee
Molecular Pharmacology November 1, 2005, 68 (5) 1281-1290; DOI: https://doi.org/10.1124/mol.105.016055

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Research ArticleArticle

A Prodrug of Cysteine, l-2-Oxothiazolidine-4-carboxylic Acid, Regulates Vascular Permeability by Reducing Vascular Endothelial Growth Factor Expression in Asthma

Kyung Sun Lee, Hee Sun Park, Seoung Ju Park, So Ri Kim, Kyung Hoon Min, Sun Mi Jin, Kwang-Hyun Park, Uh-Hyun Kim, Chan Young Kim and Yong Chul Lee
Molecular Pharmacology November 1, 2005, 68 (5) 1281-1290; DOI: https://doi.org/10.1124/mol.105.016055
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