转化生长因子β1在慢性阻塞性肺疾病γ谷氨酰半胱氨酸合成酶表达调控中的作用

Effects of β1 in the expression and regulation of γ-glutamylcysteine synthetase in chronic obstructive pulmonary disease

谷胱甘肽（GSH）作为肺最主要的抗氧化剂在肺部抗氧化损伤中发挥着重要作用，γ谷氨酰半胱氨酸合成酶（γ-GCS）是GSH生物合成的限速酶。慢性阻塞性肺疾病以患者肺内GSH水平降低和转化生长因子（TGF）哏浓度升高为特征。TGF-β1是GSH合成强有力的抑制因子，这种抑制作用在一定程度上是通过对γ-GCSh编码基因转录过程的调控实现的。TGF—β1下调γ-GCSh表达的分子机制可能与活化蛋白（AP）-1有关。

Glutathione（GSH） as the most important antioxidant plays a major role in protecting the lung against oxidative stress, Glutamylcysteine synthetase（γ-GCS） is the rate-limiting enzyme in de nove GSH synthesis. Chronic obstructive pulmonary disease is characterized by elevated concentrations of transforming growth factor —β1 （TGF -β1 ） and depleted levels of GSH in lungs of patients. TGF-β1 is a strong inhibitor of GSH synthesis. TGF —β1 down regulates the expression of γ-GCS-h at the transcriptional level. TGF —β1 may decrease γ-GCS-h gene expression via an AP-1 mechanism.