Morales A, Miranda M, Sanchez-Reyes A, Colell A, Biete A, Fernández-Checa J C
Instituto de Investigaciones Biomédicas, August Pi i Sunyer, CSIC-UB, Hospital Clinic i Provincial, Barcelona, Spain.
FEBS Lett. 1998 May 1;427(1):15-20. doi: 10.1016/s0014-5793(98)00381-0.
Since glutathione (GSH) protects against oxidative stress, we determined the regulation of cellular GSH by ionizing radiation in human hepatoblastoma cells, HepG2. The levels of GSH increased in irradiated HepG2 due to a greater gamma-glutamylcysteine synthetase (gamma-GCS) activity, which was paralleled by gamma-GCS heavy subunit chain (gamma-GCS-HS) mRNA levels. Transcription of deletion constructs of the gamma-GCS-HS promoter cloned in a reporter vector was associated with activator protein-1 (AP-1), consistent with the DNA binding of AP-1 in nuclear extracts of irradiated HepG2. Hence, the transcriptional regulation of gamma-GCS by ionizing radiation emerges as an adaptive mechanism, which may be of significance to control the consequences of the oxidative stress induced by radiation.
由于谷胱甘肽（GSH）可抵御氧化应激，我们在人肝癌细胞HepG2中测定了电离辐射对细胞内GSH的调节作用。受辐照的HepG2细胞中GSH水平升高，这是由于γ-谷氨酰半胱氨酸合成酶（γ-GCS）活性增强所致，同时γ-GCS重亚基链（γ-GCS-HS）的mRNA水平也相应升高。克隆到报告载体中的γ-GCS-HS启动子缺失构建体的转录与激活蛋白-1（AP-1）相关，这与辐照后的HepG2细胞核提取物中AP-1的DNA结合情况一致。因此，电离辐射对γ-GCS的转录调节是一种适应性机制，这对于控制辐射诱导的氧化应激后果可能具有重要意义。
