Journal article
Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1 following ionizing radiation
Cancer research (Chicago, Ill.), Vol.61(14), pp.5537-5543
2001
PMID: 11454704
Abstract
Fibrosis is a common form of normal tissue damage after exposure to a wide variety of insults believed to involve oxidative stress. Plasminogen activator inhibitor-1 (PAI-1) is thought to play a major role in the development of progressive fibrosis via the inhibition of extracellular matrix degradation. Because radiation causes oxidative injury, which has been shown to trigger fibrogenic responses, the present study was designed to test the hypothesis that PAI-1 expression is redox-regulated after irradiation. Irradiating rat kidney tubule epithelial cells (NRK52E) with 1-20 Gy gamma-rays led to dose-dependent increases in steady-state levels of PAI-1 mRNA and immunoreactive protein within 24 and 48 h, respectively. Enhancement of intracellular soluble thiol pools after incubation with N-acetylcysteine (2.5 mM), from 3.27 +/- 0.27 nM/mg protein to 5.34 +/- 0.52 nM/mg protein in cells incubated with N-acetylcysteine 30 min before and assessed 4 h after irradiation, abolished the radiation-induced up-regulation of PAI-1. In addition, overexpression of catalase inhibited radiation-induced increases in PAI-1 expression, suggesting a mechanistic role for hydrogen peroxide (H2O2) in regulating PAI-1 expression after oxidative insult. In support of this notion, incubating NRK52E cells with H2O2 (100 microM) also led to a nearly 3-fold increase in PAI-1 gene expression. These results demonstrate that PAI-1 is redox-regulated after exposure to ionizing radiation or H2O2 and suggest that H2O2 scavenging might represent a fundamental mechanism for modulating fibrogenic disease via inhibition of the induction of profibrogenic mediators after acute or chronic oxidative stress.
Details
- Title: Subtitle
- Redox modulation of the pro-fibrogenic mediator plasminogen activator inhibitor-1 following ionizing radiation
- Creators
- WEILING ZhaoDouglas R SpitzLarry W OberleyMike E. C Robbins
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.61(14), pp.5537-5543
- Publisher
- American Association for Cancer Research
- PMID
- 11454704
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2001
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312976602771
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