Positive correlation between PPARγ/PGC-1α and γ-GCS in lungs of rats and patients with chronic obstructive pulmonary disease

Authors:
  • RHRuicheng Hu
    Ruicheng Hu
  • LZLiming Zhu
    Liming Zhu
  • STShuangxiang Tan
    Shuangxiang Tan
Publisher website
Google Scholar
Abstract
Oxidative stress is one of the major pathogenesis of chronic obstructive pulmonary disease (COPD). γ-Glutamylcysteine synthetase (γ-GCS) is one of the paramount antioxidant enzymes in COPD. Peroxisome proliferator-activated receptor-gamma (PPARγ) is a ligand-activated transcription factor, which is activated by specific ligands such as rosiglitazone (RGZ), exerting multiple biological effects. PPARγ coactivator-1α (PGC-1α) is a PPARγ coactivator, which binds to PPARγ by induction of PPARγ ligands, co-activating PPARγ target genes. Growing evidence has suggested that PPARγ/PGC-1α can regulate multiple antioxidant genes. However, the effect of PPARγ/PGC-1α on γ-GCS during the development of COPD remains unclear. Here, we measured the expression levels of PPARγ, PGC-1α and γ-GCS, γ-GCS activity and reactive oxygen species (ROS) contents in lungs of rats treated by cigarette smoke (CS) + lipopolysaccharide (LPS) and CS + LPS + RGZ, as well as lungs of patients suffered from COPD. Compared with lungs from CS + LPS-treated rats, lungs of RGZ-treated rats demonstrated markedly lower ROS contents, and remarkable increase of γ-GCS activity and increase of the expression levels of PPARγ, PGC-1α, and γ-GCS. Furthermore, compared with controls, expression levels of PPARγ, PGC-1α, and γ-GCS significantly increased in the lungs of mild COPD patients, and progressively decreased in lungs of patients with moderate and severe COPD. γ-GCS protein was positively correlated with FEV1%. PPARγ and PGC-1α proteins were positively correlated with γ-GCS activity and mRNA level. In conclusion, γ-GCS showed compensatory upregulation in the early stage of COPD, which progressively decompensate with increasing COPD severity. The activation of the PPARγ/PGC-1α pathway may protect against COPD progression by upregulating γ-GCS and relieving oxidative stress.

This publication has 16 references indexed in Scilit: