Transcriptional regulation of the heavy subunit chain of γ‐glutamylcysteine synthetase by ionizing radiation

FEBS Letters

Colell, Anna¹  Miranda, Merce¹  Morales, Albert¹  Biete, Albert²  Fernández-Checa, José C¹  Sanchez-Reyes, Alberto² 

[1] Instituto de Investigaciones Biomédicas, August Pi i Sunyer, CSIC-UB and Liver Unit, Hospital Clinic i Provincial, Villarroel 170, 08036 Barcelona, Spain;Radiotherapy Unit, Hospital Clinic i Provincial, Universidad de Barcelona, 08036 Barcelona, Spain

关键词: Oxidative stress;    Gene regulation;    Glutathione;    Transcription factor;    Radiobiology;    NF-κB;    AP-1;    ARE;    antioxidant responsive element;    BSO;    buthionine-sulfoximine;    CAT;    chloramphenicol acetyl transferase;    DCFDA;    2′-7′-dichlorofluorescin diacetate;    γ-GCS-HS;    γ-glutamylcysteine synthetase heavy subunit;    GSH;    reduced glutathione;    GSSG;    oxidized glutathione;    Mn-SOD;    manganese superoxide dismutase;    MRE;    metal response element;    NF-κB;    transcription factor kappa-B;    ROS;    reactive oxygen species;    XRE;    xenobiotic response element;   

DOI  :  10.1016/S0014-5793(98)00381-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 γ-glutamylcysteine synthetase (γ-GCS) activity, which was paralleled by γ-GCS heavy subunit chain (γ-GCS-HS) mRNA levels. Transcription of deletion constructs of the γ-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 γ-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.

【 授权许可】

Unknown