Up-regulation of glutamate-cysteine ligase gene expression by butylated hydroxytoluene is mediated by transcription factor AP-1

Biochemical and Biophysical Research Communications
Z Tu, M W Anders

Abstract

Several regulatory elements, including AP-1 and NF-kappa B, are present in the 5'flanking region of the human glutamatex-cysteine ligase (EC 6.3.2.2, gamma-glutamyl-cysteine synthetase) catalytic subunit (GLCLC) gene. In this study, we investigated the role of redox-sensitive transcription factors in the regulation of GLCLC gene expression in LLC-PK1 cells that were exposed to the antioxidant butylated hydroxytoluene (BHT). Exposure of LLC-PK1 cells to 100 microM BHT induced expression of transcription factor AP-1, as demonstrated by an electrophoretic mobility shift assay. Peak AP-1 induction occurred after 3 h of incubation with BHT, BHT increased luciferase gene expression in cells that were transfected with a luciferase reporter vector containing an AP-1 element upstream of a SV40 promoter. Northern analysis showed that transcription of GLCLC gene in cells after incubation with BHT was increased 30% compared with control cells. Cellular glutathione concentrations were also significantly increased in cells exposed to BHT. In contrast, exposure of LLC-PK1 cells to 100 microM BHT did not alter expression of the transcription factor NF-kappa B. These results show that induction of transcription factor AP-1 by BHT is involved in...Continue Reading

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Sep 23, 1997·Biochemical and Biophysical Research Communications·Z Tu, M W Anders

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Citations

Aug 24, 1999·The European Journal of Neuroscience·V Ramírez-LeónB Ulfhake
Jan 10, 2004·Antioxidants & Redox Signaling·Jason M Hansen, Craig Harris
Jan 15, 2005·Antioxidants & Redox Signaling·Irfan RahmanH J Forman
Jan 8, 2011·Experimental Lung Research·Manuella LanzettiSamuel Santos Valenca
Dec 13, 2005·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·L A FaineE L B Novelli
Jun 6, 2003·Journal of Biochemistry and Molecular Biology·Su-Jung KimChang-Jin Lim
Sep 2, 2008·Molecular Aspects of Medicine·Saibal K Biswas, Irfan Rahman
Jan 7, 2000·Journal of Cellular Physiology·S R SoltaninassabM L Freeman
Dec 22, 1999·The American Journal of Physiology·I Rahman, W MacNee

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