Van Klaveren R J, Dinsdale D, Pype J L, Demedts M, Nemery B
Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium.
Am J Physiol. 1997 Sep;273(3 Pt 1):L537-47. doi: 10.1152/ajplung.1997.273.3.L537.
The effect of hyperoxia on gamma-glutamyltransferase (gamma-GT), an important enzyme for the uptake of precursor molecules for intracellular synthesis of glutathione (GSH), has not been established. Our aim was to investigate the effects of prolonged subtoxic levels of hyperoxia on gamma-GT activity and GSH levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Seventeen male Wistar rats were divided in three groups (n = 5-7) and were exposed to air or to 60 or 85% O2 for 7 days. Pulmonary gamma-GT activity increased in the 60 and 85% O2-exposed animals (1.6- and 3.2-fold, respectively), and tissue GSH levels increased only in the 60% O2 group (1.3-fold). In isolated type II cells from 60 and 85% O2-exposed animals, gamma-GT activity decreased by -70 and -88%, respectively, which was supported by cytochemical staining. Type II cell gamma-GT mRNA expression tended only to decrease after 85% O2. Type II cell gamma-GT activity strongly correlated with ELF gamma-GT (r = 0.60, P < 0.001), and ELF gamma-GT strongly correlated with ELF GSH (r = 0.75, P < 0.0001). When in culture, type II cell gamma-GT activity and GSH levels remained, respectively, 2.5- and 1.9-fold lower in the 60% O2-exposed group, but, in the 85% O2-exposed group, gamma-GT activity increased 2.1-fold, and GSH levels dropped to the levels of the control cells. Hyperoxia led to a concentration-dependent decrease in gamma-GT activity in rat type II cells, possibly by direct inactivation, but led to an increase in whole lung tissue gamma-GT. There seemed to be a negative feedback between intracellular GSH levels and type II cell gamma-GT activity. gamma-GT levels in the ELF were correlated with type II cell gamma-GT activity, but ELF gamma-GT did not seem to play an active role in the regulation of the ELF GSH pool. Hyperoxia decreased ELF GSH levels, possibly by increased degradation of GSH in the parenchymal lung tissue as a result of the increased gamma-GT activity.
高氧对γ-谷氨酰转移酶（γ-GT）的影响尚未明确，γ-GT是细胞内合成谷胱甘肽（GSH）摄取前体分子的一种重要酶。我们的目的是研究长时间亚毒性水平的高氧对肺组织、上皮衬液（ELF）以及分离的大鼠II型细胞中γ-GT活性和GSH水平的影响，观察时间点为刚分离后以及在常氧培养48小时后。17只雄性Wistar大鼠分为三组（n = 5 - 7），分别暴露于空气、60%或85%氧气中7天。暴露于60%和85%氧气的动物肺组织γ-GT活性增加（分别增加1.6倍和3.2倍），组织GSH水平仅在60%氧气组增加（增加1.3倍）。在从暴露于60%和85%氧气的动物分离出的II型细胞中，γ-GT活性分别降低了70%和88%，细胞化学染色证实了这一点。85%氧气暴露后II型细胞γ-GT mRNA表达仅呈下降趋势。II型细胞γ-GT活性与ELFγ-GT密切相关（r = 0.60，P < 0.001），ELFγ-GT与ELF GSH密切相关（r = 0.75，P < 0.0001）。在培养过程中，60%氧气暴露组II型细胞γ-GT活性和GSH水平分别比对照组低2.5倍和1.9倍，但在85%氧气暴露组，γ-GT活性增加2.1倍，GSH水平降至对照细胞水平。高氧导致大鼠II型细胞中γ-GT活性呈浓度依赖性降低，可能是通过直接失活，但导致全肺组织γ-GT增加。细胞内GSH水平与II型细胞γ-GT活性之间似乎存在负反馈。ELF中的γ-GT水平与II型细胞γ-GT活性相关，但ELFγ-GT似乎在ELF GSH池的调节中不发挥积极作用。高氧降低了ELF GSH水平，可能是由于肺实质组织中γ-GT活性增加导致GSH降解增加。
