aPKC and ERK regulate NRF2-?-GCS in rat lung with chronic obstructive pulmonary disease / 中国病理生理杂志

ABSTRACT

AIM: To investigate atypical protein kinase C(aPKC), extracellular signal regulated kinnase (ERK) regulating NF-E2-related factor 2 (NRF2)-?-gutamylcysteine synthetase (?-GCS) and the effect on lung of rats with chronic obstructive pulmonary disease (COPD). METHODS: The rat COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoke daily. The ?-GCS activity was measured. The expression of ?-GCS mRNA in lung tissue was examined by in situ hybridization (ISH) and reverse transcription-polymerase chain reaction (RT-PCR). The protein expressions of p-aPKC?/?, p-ERK, NRF2 and ?-GCS in lung tissue were detected by immunohistochemistry (IH) and Western blotting, respectively. RESULTS: (1) The ?-GCS activity was higher in COPD group than that in control group. (2) The expression of ?-GCS mRNA in the COPD group was stronger than that in control group. ISH showed that the ?-GCS mRNA was expressed in alveolar epithelium and bronchiolar smooth muscle cell in the COPD group. (3) The protein expressions of p-aPKC, p-ERK, NRF2, ?-GCS were significantly higher than those in control group. IH showed that p-aPKC, p-ERK, NRF2, ?-GCS proteins were expressed in alveolar and bronchiolar epithelium in the COPD group. (4) There was a positive correlation between NRF2 and ?-GCS. ?-GCS mRNA, p-aPKC?/?, p-ERK were also positively correlated with NRF2. CONCLUSION: By upregulating the signal transduction of NRF2-?-GCS, the ERK and aPKC?/? may play an important role in the mechanism of COPD formation.