[Changes of the activity and expression of gamma-glutamylcysteine synthetase in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the oxidative/antioxidative status in patients with chronic obstructive pulmonary disease (COPD), and to study the expression and location of gamma-glutamylcysteine synthetase (gamma-GCS) in lung tissues.

METHODS: (1) Serum samples of 13 patients with COPD in exacerbation and 9 healthy non-smokers were collected for measurements of the level of reduced glutathione (GSH), reactive oxygen species (ROS), total antioxidative capacity (T-AOC) and gamma-GCS activity. (2) Lung tissues from 22 patients (12 patients with COPD and 10 patients as control) undergoing resection for lung tumor were collected for study of the expression and location of gamma-GCS and gamma-GCS mRNA by immunohistochemistry and in situ hybridization, respectively.

RESULTS: (1) Significantly decreased level of GSH [(23.87 +/- 3.86) mg/ml], increased level of ROS [(2 463 +/- 199) U/ml], decreased T-AOC [(5.34 +/- 0.22) U/ml] and enhanced activity of gamma-GCS [(19.22 +/- 3.36) U/ml] were shown in the serum of patients with an acute exacerbation of COPD, as compared to the control group [(36.87 +/- 6.34) mg/ml, (1 023 +/- 112) U/ml, (11.36 +/- 1.07) U/ml and (12.37 +/- 2.96) U/ml, respectively, all P < 0.05]. (2) There was no relationship between the level of GSH, ROS, T-AOC, gamma-GCS activity in serum and FEV1%, FEV1/FVC, PaO2, PaCO2 of patients with COPD in exacerbation (P > 0.05). (3) In situ hybridization showed that the expressions of gamma-GCS mRNA in alveoli, bronchi and inflammatory cells (A value was 0.29 +/- 0.05, 0.31 +/- 0.05 and 0.28 +/- 0.06, respectively) from the COPD group were stronger than those from the control group (0.14 +/- 0.03, 0.17 +/- 0.04 and 0.20 +/- 0.05, respectively) by semi-quantitative analysis (all P < 0.05). (4) By immunohistochemistry, the expressions of gamma-GCS was significantly higher in alveoli (0.20 +/- 0.04), bronchi (0.18 +/- 0.02) and inflammatory cells (0.25 +/- 0.06) in the COPD group as compared to the control group (0.12 +/- 0.04, 0.10 +/- 0.03 and 0.14 +/- 0.04, respectively, all P < 0.05). (5) Negative correlations were shown between gamma-GCS and FEV1%, FEV1/FVC (r = - 0.501 and - 0.542, respectively, P < 0.05), while the level of gamma-GCS expression had no correlation with FEV1% and FEV1/FVC (r = - 0.221 and - 0.148, respectively, P > 0.05), and a positive relationship was observed between gamma-GCS and gamma-GCS mRNA (r = 0.732, P < 0.05).

CONCLUSIONS: Systemic oxidative/antioxidative imbalance occurs in patients with acute exacerbation of COPD, and the total antioxidative capacity decrease may not correlate significantly to the obstruction of airways, in spite of the high level of gamma-GCS activity in serum and gamma-GCS expression in the lungs.