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Publication : The redox-sensitive human antioxidant responsive element induces gene expression under low oxygen conditions.

First Author  Waleh NS Year  1998
Journal  Carcinogenesis Volume  19
Issue  8 Pages  1333-7
PubMed ID  9744525 Mgi Jnum  J:50131
Mgi Id  MGI:1289946 Doi  10.1093/carcin/19.8.1333
Citation  Waleh NS, et al. (1998) The redox-sensitive human antioxidant responsive element induces gene expression under low oxygen conditions. Carcinogenesis 19(8):1333-7
abstractText  Transient transfection studies of human HepG2 and mouse Hepa hepatocarcinoma cells with a reporter gene construct regulated by a human antioxidant responsive element (ARE) from the NQO1 gene demonstrated that the element is responsive to low oxygen conditions. The antioxidant N-acetyl L-cysteine (NAC) strongly inhibited basal aerobic reporter gene activity in HepG2 cells without obviously affecting the hypoxic induction, as is consistent with ARE sensitivity to oxidative stress in aerobic cultures. Electrophoretic mobility shift (EMS) assays of nuclear extracts of HepG2 and Hepa cells lysed under aerobic or hypoxic conditions or after exposure to the phenolic compound 3-(2)-tert-butyl-4-hydroxyanisole (BHA), showed specific and constitutive protein binding to the ARE under all of these conditions. Taken together, these findings show that the ARE can mediate gene expression in response to low oxygen conditions. Co-ordinately regulated expression of ARE-dependent genes, such as phase II detoxification enzymes, may be an important phenotype of solid tumors containing significant regions of pathophysiological hypoxia.
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