Differential regulation of the rainbow trout ( Oncorhynchus mykiss ) MT-A gene by nuclear factor interleukin-6 and activator protein-1
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TLDR
The involvement of NF-IL6 and AP1 in rtMT-A gene expression following exposure to oxidative stress and tumour promotion suggests an involvement of MT in protection during pathological processes such as inflammation and cancer.Abstract:
Previously we have identified a distal region of the rainbow trout (Oncorhynchus mykiss) metallothionein-A (rtMT-A) enhancer region, being essential for free radical activation of the rtMT-A gene. The distal promoter region included four activator protein 1 (AP1) cis-acting elements and a single nuclear factor interleukin-6 (NF-IL6) element. In the present study we used the rainbow trout hepatoma (RTH-149) cell line to further examine the involvement of NF-IL6 and AP1 in rtMT-A gene expression following exposure to oxidative stress and tumour promotion. Using enhancer deletion studies we observed strong paraquat (PQ)-induced rtMT-A activation via NF-IL6 while the AP1 cis-elements showed a weak but significant activation. In contrast to mammals the metal responsive elements were not activated by oxidative stress. Electrophoretic mobility shift assay (EMSA) mutation analysis revealed that the two most proximal AP1 elements, AP11,2, exhibited strong binding to the AP1 consensus sequence, while the more distal AP1 elements, AP13,4 were ineffective. Phorbol-12-myristate-13-acetate (PMA), a known tumor promoter, resulted in a robust induction of rtMT-A via the AP1 elements alone. To determine the conservation of regulatory functions we transfected human Hep G2 cells with the rtMT-A enhancer constructs and were able to demonstrate that the cis-elements were functionally conserved. The importance of NF-IL6 in regulation of teleost MT is supported by the conservation of these elements in MT genes from different teleosts. In addition, PMA and PQ injection of rainbow trout resulted in increased hepatic rtMT-A mRNA levels. These studies suggest that AP1 primarily is involved in PMA regulation of the rtMT-A gene while NF-IL6 is involved in free radical regulation. Taken together this study demonstrates the functionality of the NF-IL6 and AP-1 elements and suggests an involvement of MT in protection during pathological processes such as inflammation and cancer.read more
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Environmental monitoring of urban streams using a primary fish gill cell culture system (FIGCS)
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Response to metals treatment of Fra1, a member of the AP-1 transcription factor family, in P. lividus sea urchin embryos.
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References
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Journal ArticleDOI
Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene
TL;DR: It is reported here that Jun, Fos, Fra, and NRF nuclear transcription factors bind to the hARE, indicating that hARE-mediated expression of the NQO1 gene and its induction by xenobiotics and antioxidants are mediated by Nrf1 and Nrf2.
Journal ArticleDOI
Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals
TL;DR: Metallothionein has the characteristics of a sacrificial but renewable cellular target for .OH-mediated cellular damage, and appears to be an extraordinarily efficient .OH radical scavenger even when compared to proteins 10-50-times its molecular weight.
Journal ArticleDOI
Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8.
Taiji Matsusaka,Keiko Fujikawa,Yukihiro Nishio,Naofumi Mukaida,Koji Matsushima,Tadamitsu Kishimoto,Shizuo Akira +6 more
TL;DR: The synergistic activation of the IL-6 promoter by transcription factors NF-IL6 and NF-kappa B and the possible interplay between various viral gene products and these two factors in the process of viral infection and constitutive cytokine production is discussed.
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Regulation of metallothionein gene expression by oxidative stress and metal ions
TL;DR: The studies suggest that the DNA-binding activity of MTF-1 in vivo and in vitro is reversibly activated by zinc interactions with the zinc-finger domain, reflecting heterogeneity in the structure and function of the six zinc fingers.
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Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40
TL;DR: The identification of two cellular DNA-binding proteins that interact selectively with sequences governing the basal level expression of hMTIIA, a novel activator protein (API) that interacts with sequences in the BLE of h MTIIA and also binds to a site within the 72-base pair repeats of the simian virus 40 (SV40) enhancer region.