Roles of NRF2 regulating gamma-glutamylcysteine synthetase in lung of rats with chronic obstructive pulmonary disease.
- Author:
Lin CHEN
1
;
Ai-Guo DAI
;
Rui-Cheng HU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Glutamate-Cysteine Ligase; metabolism; Lung; metabolism; Male; NF-E2-Related Factor 2; metabolism; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; metabolism; physiopathology; Random Allocation; Rats; Rats, Wistar
- From: Chinese Journal of Applied Physiology 2008;24(3):339-342
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo investigate the expression and relationship of gamma-glutamylcysteine synthetase (gamma-GCS) and NF-E2-related factor2 (NRR2) in lung of rat with chronic obstructive pulmonary disease (COPD)in order to elucidate the possible important role of gamma-GCS and NRF2 in pathogenesis of COPD.
METHODSThe rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposed to cigarette smoke daily. The gamma-GCS activity was measured, the expression of gamma-GCS mRNA in lung was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR), the protein expressions of NRF2, gamma-GCS in lung were detected by immunohistochemical (IH) and Western blot respectively.
RESULTSThe gamma-GCS activity was higher in COPD group than that in control group. The expressions of gamma-GCS mRNA in COPD group was stronger than those in control group. ISH showed that the gamma-GCS mRNA was expressed in alveolar epithelium and bronchial smooth muscle cell in COPD. The protein expressions of NRF2, gamma-GCS were significantly higher than the control group. IH showed that NRF2, gamma-GCS proteins were expressed in alveolar and bronchial epithelium in the COPD group. There was a positive correlation between NRF2 and gamma-GCS and gamma-GCS mRNA.
CONCLUSIONNRF2 may play an important role in the mechanism of COPD oxidative stress vis up-regulation of gamma-GCS.