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Journal Article•DOI•

Differential regulation of the rainbow trout ( Oncorhynchus mykiss ) MT-A gene by nuclear factor interleukin-6 and activator protein-1

Peter Kling1, Carina Modig2, Huthayfa Mujahed2, Hazem Khalaf2, Jonas von Hofsten3, Per-Erik Olsson2 •
University of Gothenburg1, Örebro University2, Umeå University3
17 Dec 2013-BMC Molecular Biology (BioMed Central)-Vol. 14, Iss: 1, pp 28-28
TL;DR: 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.

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Citations
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Journal Article•DOI•
Environmental monitoring of urban streams using a primary fish gill cell culture system (FIGCS)

[...]

Sabine Schnell1, K. A. Bawa-Allah2, Adebayo A. Otitoloju2, Christer Hogstrand1, Thomas H. Miller1, Leon Barron1, Nic Bury1 •
King's College London1, University of Lagos2
01 Oct 2015-Ecotoxicology and Environmental Safety
TL;DR: The primary fish gill cell culture system (FIGCS) is an in vitro technique which has the potential to replace animals in whole effluent toxicity tests and the increase in the expression of genes encoding mta, cyp1a1 and cyp3a27 in FIGCS is indicative of the presence of biologically active pollutants.

19 citations

Cites background from "Differential regulation of the rain..."

  • ...The distal region of the rainbow 319 trout mta promoter possess both activator protein 1 (AP1) and a nuclear factor interleukin-6 320 (NF-IL6) elements that have been shown to play a direct role in mta induction in response to 321 paraquat, an herbicide that induces ROS (Kling et al., 2013)....

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  • ...Some pharmaceuticals and personal care products 316 have been shown to affect reactive oxygen species(ROS) production in rainbow trout gonad 317 cell line (RTG-2) (Fernandez et al., 2013) and PAHs are known to induce free radical 318 production (e.g. Wells and Winn 1996; Zhu et al., 2014)....

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  • ...Effects of human 402 pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes....

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  • ...In addition, FIGCS treated with 322 H2O2, that produces ROS, show an increase in mta and b gene expression, as well as other 323 antioxidant genes (Chung et al., 2005)....

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  • ...The antioxidant gene expression is attenuated by the 324 14 zinc chelator N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), suggesting that the 325 response to ROS in FIGCS is in part mediated by an increase in intracellular zinc 326 concentrations (Chung et al., 2005)....

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Journal Article•DOI•
Genetic polymorphism of metallothionein 2A and risk of laryngeal cancer in a Polish population.

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Katarzyna Starska, Anna Krześlak, Ewa Forma, Jurek Olszewski, Iwona Lewy-Trenda, Ewa Osuch-Wójcikiewicz1, Magdalena Bryś •
Medical University of Warsaw1
22 Jun 2014-Medical Oncology
TL;DR: The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.
Abstract: Metallothioneins are intracellular regulators of many biological mechanisms including differentiation, proliferation, angiogenesis and invasion, which are crucial processes in carcinogenesis. This study examines the association between three single-nucleotide polymorphisms at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the metallothionein 2A (MT2A) gene with squamous cell laryngeal cancer (SCLC) risk, as well as with tumor invasiveness according to tumor front grading (TFG). Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism technique in 323 genetically unrelated individuals with SCLC and 418 randomly selected healthy volunteers. Only one SNP (rs28366003) was significantly related to laryngeal cancer in the study population. Compared with homozygous common allele carriers, heterozygous and homozygous for the G variant had significantly increased risk of SCLC [adjusted odds ratio (OR) = 2.90, 95 % confidence interval (CI) 1.53-5.21, p dominant 18 points) (OR = 3.76, 95 % CI 1.15-12.56, p = 0.03) and diffuse tumor growth (OR = 5.86, 95 % Cl 0.72-44.79, p = 0.08). The results of this study raise a possibility that a genetic variation of MT2A may be implicated in the etiology of laryngeal cancer in a Polish population.

14 citations

Cites background from "Differential regulation of the rain..."

  • ...MT promoter activity is regulated by six zinc-finger metalresponsive transcription factor (MTF-1) and a nuclear factor I (NF-I) protein [2]....

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Journal Article•DOI•
Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma)

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Katarzyna Starska, Magdalena Bryś, Ewa Forma, Jurek Olszewski, Piotr Pietkiewicz, Iwona Lewy-Trenda, Olga Stasikowska-Kanicka, Marian Danilewicz, Anna Krześlak 
03 Jun 2015-Tumor Biology
TL;DR: The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.
Abstract: Inverted papillomas are a unique group of locally aggressive benign epithelial neoplasms in the nasal cavity and paranasal sinuses arising from the Schneiderian mucosa. Metallothioneins are sulfhydryl-rich heavy metal-binding proteins required for metal toxicity protection and regulation of biological mechanisms including proliferation and invasion. The goal of this study was to identify three SNPs at loci −5 A/G (rs28366003) and −209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3′UTR region of the MT2A gene with IP risk and with tumor invasiveness according to Krouse staging. Genotyping was performed using the PCR restriction fragment length polymorphism technique in 130 genetically unrelated IP individuals, and 418 randomly selected healthy volunteers. The presence of the rs28366003 SNP was significantly related to the risk of IP within the present population-based case-control study. Compared to homozygous common allele carriers, heterozygosity and homozygosity for the G variant had a significantly increased risk of IP (adjusted odds ratio [OR] = 7.71, 95 % confidence interval [CI]: 4.01–14.91, p dominant < 0.001). Moreover, risk allele carriers demonstrated higher Krouse stage (pT1 vs. pT2-4) (OR = 19.32; 95 % CI, 2.30–173.53; p < 0.0001), diffuse tumor growth (OR = 4.58; 95 % CI, 1.70–12.11; p = 0.0008), bone destruction (OR = 4.13; 95 % CI, 1.50–11.60; p = 0.003), and higher incidence of tumor recurrences (OR = 5.11; 95 % CI, 1.68–15.20; p = 0.001). The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.

13 citations

Cites background from "Differential regulation of the rain..."

  • ...er region is played by the six zinc-finger-metal-responsive transcription factor (MTF-1) and short cis-acting DNA metal response elements (MREs) as transcriptional activators and a nuclear factor I (NF-I) protein as a downregulator of MT expression [11]....

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Journal Article•DOI•
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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Roberta Russo, Rosa Bonaventura, Marco Chiaramonte, Caterina Costa, Valeria Matranga, Francesca Zito 
01 Aug 2018-Marine Environmental Research
TL;DR: Interestingly, Pl-Fra expression was induced by the different metals and the induction kinetics revealed its persistent expression during treatments, and its temporal and spatial behavior in response to the three metals was comparable to that of Pl-jun and Pl-MT.

12 citations

Journal Article•DOI•
Immune stimulation of rainbow trout reveals divergent regulation of MH class II-associated invariant chain isoforms.

[...]

Shawna L. Semple1, George Heath1, Darah Christie1, Marsela Braunstein1, Stephen C. Kales1, Brian Dixon1 •
University of Waterloo1
29 Apr 2019-Immunogenetics
TL;DR: Results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals.
Abstract: Major histocompatibility complex (MHC) class II-associated invariant chain is a chaperone responsible for targeting the MHC class II dimer to the endocytic pathway, thus enabling the loading of exogenous antigens onto the MHC class II receptor. In the current study, in vivo and in vitro methods were used to investigate the regulation of the rainbow trout invariant chain proteins S25-7 and INVX, upon immune system activation. Whole rainbow trout and the macrophage/monocyte-like cell line RTS11 were treated with PMA at concentrations shown to induce IL-1β transcripts and homotypic aggregation of RTS11. S25-7 transcript levels remained unchanged in the gill, spleen, and liver and were found to be significantly decreased in head kidney beginning 24 h post-stimulation. Meanwhile, INVX transcript levels remained unchanged in all tissues studied. Both S25-7 and INVX proteins were produced in gill and spleen tissues but their expression was unaffected by immune system stimulation. Surprisingly, neither INVX nor S25-7 protein was detected in the secondary immune organ, the head kidney. Analysis of RTS11 cultures demonstrated that both INVX and S25-7 transcript levels significantly increased at 96 h and 120 h following PMA stimulation before returning to control levels at 168 h. Meanwhile, at the protein level in RTS11, S25-7 remained unchanged while INVX had a significant decrease at 168 h post-stimulation. These results indicate that neither INVX nor S25-7 is upregulated upon immune system activation; thus, teleosts have evolved a system of immune regulation that is different than that found in mammals.

11 citations

References
More filters
Journal Article•DOI•
Analyzing real-time PCR data by the comparative C(T) method.

[...]

Thomas D. Schmittgen1, Kenneth J. Livak2•
Ohio State University1, Applied Biosystems2
01 Jan 2008-Nature Protocols
TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this method.
Abstract: Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.

20,580 citations

"Differential regulation of the rain..." refers methods in this paper

  • ...Relative gene-expression was determined by using the ΔΔCt method [49]....

    [...]

Journal Article•DOI•
Whole-Genome Shotgun Assembly and Analysis of the Genome of Fugu rubripes

[...]

Samuel Aparicio1, Jarrod Chapman1, Elia Stupka1, Nik Putnam1, Jer Ming Chia1, Paramvir S. Dehal1, Alan Christoffels1, Sam Rash1, Shawn Hoon1, Arian F.A. Smit1, Maarten D. Sollewijn Gelpke1, Jared C. Roach1, Tania Oh1, Isaac Ho1, Marie Wong1, Chris Detter1, Frans Verhoef1, Paul Predki1, Alice Tay1, Susan Lucas1, Paul G. Richardson1, Sarah Smith1, Melody S. Clark1, Yvonne J. K. Edwards1, Norman A. Doggett1, Andrey Zharkikh1, Sean V. Tavtigian1, Dmitry Pruss1, Mary Barnstead1, Cheryl Evans1, Holly Baden1, Justin Powell1, Gustavo Glusman1, Lee Rowen1, Leroy Hood1, Y. H. Tan1, Greg Elgar1, Trevor Hawkins1, Byrappa Venkatesh1, Daniel S. Rokhsar1, Sydney Brenner1 •
Agency for Science, Technology and Research1
23 Aug 2002-Science
TL;DR: The Fugu rubripes genome has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds as discussed by the authors.
Abstract: The compact genome of Fugu rubripes has been sequenced to over 95% coverage, and more than 80% of the assembly is in multigene-sized scaffolds. In this 365-megabase vertebrate genome, repetitive DNA accounts for less than one-sixth of the sequence, and gene loci occupy about one-third of the genome. As with the human genome, gene loci are not evenly distributed, but are clustered into sparse and dense regions. Some “giant” genes were observed that had average coding sequence sizes but were spread over genomic lengths significantly larger than those of their human orthologs. Although three-quarters of predicted human proteins have a strong match toFugu, approximately a quarter of the human proteins had highly diverged from or had no pufferfish homologs, highlighting the extent of protein evolution in the 450 million years since teleosts and mammals diverged. Conserved linkages between Fugu and human genes indicate the preservation of chromosomal segments from the common vertebrate ancestor, but with considerable scrambling of gene order.

1,446 citations

"Differential regulation of the rain..." refers background in this paper

  • ...Sequencing of the Fugu genome allowed determination of gene similarity between human and teleost genomes [18]....

    [...]

Journal Article•DOI•
The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity.

[...]

Thomas H. Rushmore1, M.R. Morton1, Cecil B. Pickett1•
Merck & Co.1
25 Jun 1991-Journal of Biological Chemistry
TL;DR: The data suggest that the sequence, 5'-puGTGACNNNGC-3' 3'-pyCACTGNNNCG-5' where N is any nucleotide, represents the core sequence of the ARE required for transcriptional activation by phenolic antioxidants and metabolizable planar aromatic compounds.

1,404 citations

Journal Article•DOI•
Transcription Factor Nrf2 Coordinately Regulates a Group of Oxidative Stress-inducible Genes in Macrophages

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Tetsuro Ishii1, Ken Itoh1, Satoru Takahashi1, Hideyo Sato1, Toru Yanagawa1, Yasutake Katoh1, Shiro Bannai1, Masayuki Yamamoto1 •
University of Tsukuba1
26 May 2000-Journal of Biological Chemistry
TL;DR: It is shown that Nrf2 controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane transport (system xc −) activity.

1,367 citations

"Differential regulation of the rain..." refers background in this paper

  • ...However, it has been indicated that ARE driven gene expression can occur in the absence of oxidative stress through the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) [26]....

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  • ...The USF/ARE composite transcription factor has also been identified in a number of other terrestrial vertebrates including chicken [21]....

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  • ...While free radical regulation of mammalian MT genes seem to be mediated via USF/ARE and MRE cis-acting elements [20], teleost MT genes may be regulated via conserved clusters of cis-acting elements sharing high homology to the NF-IL6 and the AP1 consensus core sequences [7,11,12]....

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  • ...The ARE cis-acting element has also been identified and characterized in enhancer regions from metabolizing enzymes participating in the phase II drug response and is activated by electrophilic xenobiotics and H2O2 [23]....

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  • ...However, AP1 has been shown to bind to ARE in the NADP (H): quinone oxidoreductase hNQO1 gene enhancer resulting in activation of this gene [28,29]....

    [...]

Journal Article•DOI•
Radical-free biology of oxidative stress

[...]

Dean P. Jones1•
Emory University1
01 Oct 2008-American Journal of Physiology-cell Physiology
TL;DR: Data is summarized supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals, which is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation.
Abstract: Free radical-induced macromolecular damage has been studied extensively as a mechanism of oxidative stress, but large-scale intervention trials with free radical scavenging antioxidant supplements show little benefit in humans. The present review summarizes data supporting a complementary hypothesis for oxidative stress in disease that can occur without free radicals. This hypothesis, which is termed the “redox hypothesis,” is that oxidative stress occurs as a consequence of disruption of thiol redox circuits, which normally function in cell signaling and physiological regulation. The redox states of thiol systems are sensitive to two-electron oxidants and controlled by the thioredoxins (Trx), glutathione (GSH), and cysteine (Cys). Trx and GSH systems are maintained under stable, but nonequilibrium conditions, due to a continuous oxidation of cell thiols at a rate of about 0.5% of the total thiol pool per minute. Redox-sensitive thiols are critical for signal transduction (e.g., H-Ras, PTP-1B), transcription factor binding to DNA (e.g., Nrf-2, nuclear factor-κB), receptor activation (e.g., αIIbβ3 integrin in platelet activation), and other processes. Nonradical oxidants, including peroxides, aldehydes, quinones, and epoxides, are generated enzymatically from both endogenous and exogenous precursors and do not require free radicals as intermediates to oxidize or modify these thiols. Because of the nonequilibrium conditions in the thiol pathways, aberrant generation of nonradical oxidants at rates comparable to normal oxidation may be sufficient to disrupt function. Considerable opportunity exists to elucidate specific thiol control pathways and develop interventional strategies to restore normal redox control and protect against oxidative stress in aging and age-related disease.

1,067 citations

"Differential regulation of the rain..." refers background in this paper

  • ...At the cellular level the * Correspondence: per-erik.olsson@oru.se †Equal contributors 1Örebro Life Science Center, School of Science and Technology, Örebro University, Örebro SE-701 82, Sweden Full list of author information is available at the end of the article © 2013 Kling et al.; licensee BioMed Central Lt Commons Attribution License (http://creativec reproduction in any medium, provided the or oxidative stress response results in activation and up regulation of several antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione-s-transferase (GST) as well as non-enzymatic antioxidant compounds, such as ascorbic acid, β-carotene and reduced glutathione, GSH [2]....

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  • ...However, several antioxidant systems, such as GSH, SOD, catalase and MT have evolved to protect the organism from oxidative stress....

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  • ...; licensee BioMed Central Lt Commons Attribution License (http://creativec reproduction in any medium, provided the or oxidative stress response results in activation and up regulation of several antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione-s-transferase (GST) as well as non-enzymatic antioxidant compounds, such as ascorbic acid, β-carotene and reduced glutathione, GSH [2]....

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