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, Sun Park Hee, Ju Park Seoung, Ri Kim So, Kyung-Hoon Min, Mi Jin Sun, Kwang Hyun Park, Uh Hyun Kim, Young Kim Chan, Chul Lee Yong

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1281-1290
Number of pages10
JournalMolecular Pharmacology
Volume68
Issue number5
DOIs
Publication statusPublished - 2005 Nov 1
Externally publishedYes

Fingerprint

Prodrugs
Capillary Permeability
Vascular Endothelial Growth Factor A
Cysteine
Asthma
Lung
Respiratory Hypersensitivity
Reactive Oxygen Species
Inflammation
Hypoxia-Inducible Factor 1
Tissue Extracts
Ovalbumin
Nuclear Proteins
Allergens
Inhalation
Blood Vessels
Oxidative Stress
Cell Count
Antioxidants
2-oxothiazolidine-4-carboxylic acid

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma. / Lee, Kyung Sun; Hee, Sun Park; Seoung, Ju Park; So, Ri Kim; Min, Kyung-Hoon; Sun, Mi Jin; Park, Kwang Hyun; Kim, Uh Hyun; Chan, Young Kim; Yong, Chul Lee.

In: Molecular Pharmacology, Vol. 68, No. 5, 01.11.2005, p. 1281-1290.

Research output: Contribution to journalArticle

Lee, Kyung Sun ; Hee, Sun Park ; Seoung, Ju Park ; So, Ri Kim ; Min, Kyung-Hoon ; Sun, Mi Jin ; Park, Kwang Hyun ; Kim, Uh Hyun ; Chan, Young Kim ; Yong, Chul Lee. / A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma. In: Molecular Pharmacology. 2005 ; Vol. 68, No. 5. pp. 1281-1290.
@article{133ffe3ef56f4f8e94a4d5c6225745e2,
title = "A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma",
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.",
author = "Lee, {Kyung Sun} and Hee, {Sun Park} and Seoung, {Ju Park} and So, {Ri Kim} and Kyung-Hoon Min and Sun, {Mi Jin} and Park, {Kwang Hyun} and Kim, {Uh Hyun} and Chan, {Young Kim} and Yong, {Chul Lee}",
year = "2005",
month = "11",
day = "1",
doi = "10.1124/mol.105.016055",
language = "English",
volume = "68",
pages = "1281--1290",
journal = "Molecular Pharmacology",
issn = "0026-895X",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "5",

}

TY - JOUR

T1 - A prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, regulates vascular permeability by reducing vascular endothelial growth factor expression in asthma

AU - Lee, Kyung Sun

AU - Hee, Sun Park

AU - Seoung, Ju Park

AU - So, Ri Kim

AU - Min, Kyung-Hoon

AU - Sun, Mi Jin

AU - Park, Kwang Hyun

AU - Kim, Uh Hyun

AU - Chan, Young Kim

AU - Yong, Chul Lee

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27544492881&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27544492881&partnerID=8YFLogxK

U2 - 10.1124/mol.105.016055

DO - 10.1124/mol.105.016055

M3 - Article

C2 - 16103046

AN - SCOPUS:27544492881

VL - 68

SP - 1281

EP - 1290

JO - Molecular Pharmacology

JF - Molecular Pharmacology

SN - 0026-895X

IS - 5

ER -