Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding

Kaltreider, Ronald C.; Pesce, Carrie A.; Ihnat, Michael A.; Lariviere, Jean P.; Hamilton, Joshua W.

doi:10.1002/(sici)1098-2744(199907)25:3<219::aid-mc8>3.0.co;2-x

Cited by 62 publications

(9 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further analysis of upstream regulators and network revealed four hub factors, Nr2f2, Jun, Kras and ApoE (Figure 3). Moreover, many transcription factors, such as Prox1, Nr1d1, Rxrg, Hlf, Nr0b2, Foxm1, Nfn1a, Jun, Junb, Fox3, Etv5, Sqtm1, and NF-kB1b were differentially regulated by arsenic exposure in our data, consistent with reports in mammalian cells, where the AP-1 complex, NF-kB, and the MTF-1 (metal-responsive transcription factor 1) could be activated by arsenic [69]–[72].…”

Section: Discussionsupporting

confidence: 91%

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

Lam

Shen

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Inorganic arsenic is a worldwide metalloid pollutant in environment. Although extensive studies on arsenic-induced toxicity have been conducted using in vivo and in vitro models, the exact molecular mechanism of arsenate toxicity remains elusive. Here, the RNA-SAGE (serial analysis of gene expression) sequencing technology was used to analyse hepatic response to arsenic exposure at the transcriptome level. Based on more than 12 million SAGE tags mapped to zebrafish genes, 1,444 differentially expressed genes (750 up-regulated and 694 down-regulated) were identified from a relatively abundant transcripts (>10 TPM [transcripts per million]) based on minimal two-fold change. By gene ontology analyses, these differentially expressed genes were significantly enriched in several major biological processes including oxidation reduction, translation, iron ion transport, cell redox, homeostasis, etc. Accordingly, the main pathways disturbed include metabolic pathways, proteasome, oxidative phosphorylation, cancer, etc. Ingenity Pathway Analysis further revealed a network with four important upstream factors or hub genes, including Jun, Kras, APoE and Nr2f2. The network indicated apparent molecular events involved in oxidative stress, carcinogenesis, and metabolism. In order to identify potential biomarker genes for arsenic exposure, 27 out of 29 up-regulated transcripts were validated by RT-qPCR analysis in pooled RNA samples. Among these, 14 transcripts were further confirmed for up-regulation by a lower dosage of arsenic in majority of individual zebrafish. Finally, at least four of these genes, frh3 (ferrintin H3), mgst1 (microsomal glutathione S-transferase-like), cmbl (carboxymethylenebutenolidase homolog) and slc40a1 (solute carrier family 40 [iron-regulated transporter], member 1) could be confirmed in individual medaka fish similarly treated by arsenic; thus, these four genes might be robust arsenic biomarkers across species. Thus, our work represents the first comprehensive investigation of molecular mechanism of asenic toxicity and genome-wide search for potential biomarkers for arsenic exposure.

show abstract

Section: Discussionsupporting

confidence: 91%

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

Lam

Shen

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…In agreement with in vitro studies, increased AP‐1 DNA binding activity was also reported in urinary bladder epithelium of mice chronically exposed to high concentrations of iAs III (5–100 mg/L) in drinking water (42). Activating effects of iAs III on c‐Jun and c‐fos expression or AP‐1 DNA binding have been confirmed in HeLa cells (12), human embryonic kidney (HEK 293) cells (43), human breast cancer (MDA‐MB‐435) and rat hepatoma (H4IIE) cells (10), and mouse epidermal (Cl 41) cells (16), and in precision‐cut rat lung slices (44). The concentrations of iAs III used in these studies ranged from 0.1 to 300 I M. Notably, activation of c‐Jun and c‐fos expression or AP‐1 DNA binding has been observed almost exclusively at concentrations above 10 IM iAs III .…”

Section: Discussionmentioning

confidence: 90%

“…In addition, iAs modifies signal transduction pathways that are involved in the regulation of cell growth and proliferation (6). It has been shown that iAs III modulates the expression and/or DNA binding activities of several transcription factors associated with cell proliferation and death, including nuclear factor‐κB (NF‐κB) (7, 8), tumor suppressor 53 (p53) (9), a GC‐box specific transcription factor Sp1 (10), a Y‐box specific transcription factor‐1 (YB‐1) (10), and activator protein‐1 (AP‐1) (11‐13). Examination of mechanisms involved in the AP‐1 activation indicates that iAs III stimulates the mitogen‐activated protein kinase (MAPK) cascade, thus inducing expression of c‐Jun and c‐fos protooncogenes and enhancing DNA binding activity of AP‐1 (12, 14‐17).…”

mentioning

confidence: 99%

Differential activation of AP‐1 in human bladder epithelial cells by inorganic and methylated arsenicals

Drobná¹,

Jaspers²,

Thomas

et al. 2002

FASEB j.

View full text Add to dashboard Cite

Chronic exposures to inorganic arsenic (iAs) have been linked to increased incidences of various cancers, including cancer of the urinary bladder. Mechanisms by which iAs promotes cancer may include stimulation of activator protein-1 (AP-1) DNA binding through increased expression and/or phosphorylation of the AP-1 constituents. However, the role of methylated metabolites of iAs in AP-1 activation has not been thoroughly examined. In this study, we show that short-time exposures to 0.1-5 microM arsenite (iAsIII) or the methylated trivalent arsenicals methylarsine oxide (MAsIIIO), or iododimethylarsine (DMAsIIII) induce phosphorylation of c-Jun and increase AP-1 DNA binding activity in human bladder epithelial cells. DMAsIIII and especially MAsIIIO are considerably more potent than iAsIII as inducers of c-Jun phosphorylation and AP-1 activation. Phosphorylated c-Jun, JunB, JunD, and Fra-1, but not c-Fos, FosB, or ATF-2, are detected in the AP-1-DNA binding complex in cells exposed to trivalent arsenicals. In cells transiently transfected with an AP-1-dependent promoter-reporter construct, MAsIIIO was more potent than iAsIII in inducing the AP-1-dependent gene transcription. Exposures to trivalent arsenicals induce phosphorylation of extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinases or p38 kinases. These results indicate that an ERK-dependent signal transduction pathway is at least partially responsible for c-Jun phosphorylation and AP-1 activation in UROtsa cells exposed to inorganic or methylated trivalent arsenicals.

show abstract

“…Studies have shown that As (III) modulates the expression and DNA binding activities of various transcription factors associated with cell proliferation and cell death including tumor suppressor 53 (p53), nuclear factor-kB (NF-κB), a Y-box specific transcription factor-1 (YB-1), activator protein-1 (AP-1), and a GC-box specific transcription factor 1(SP-1) [Salazar et al, 1997; Barchowsky et al, 1996; Kaltreider et al, 1999; Simenova et al, 2000]. Available data suggest that As (III) may modulate AP-1 dependent gene transcription and contribute to either induction of cell proliferation or acceleration of cell death [Simenova et al, 2000; Trouba et al, 2000].…”

Section: Introductionmentioning

confidence: 99%

Arsenite causes down‐regulation of Akt and c‐Fos, cell cycle dysfunction and apoptosis in glutathione‐deficient cells

Habib

2010

J of Cellular Biochemistry

View full text Add to dashboard Cite

Arsenic is a well known environmental toxicant but the mechanism by which it causes cytotoxicity is poorly understood. Arsenite induces apoptosis in glutathione (GSH)-deficient GCS-2 cells by causing cell cycle dysfunction and down-regulating critical signaling pathways. This study was designed to examine the effect of arsenite on redox-sensitive phosphatidylinositol 3-kinase (PI3K)/Akt, a signaling pathway involved in cell survival and growth, and transcription factor, activating protein-1 (AP-1). Arsenite significantly diminished Akt and c-Fos levels and caused accelerated degradation of these proteins by ubiquitnation. Arsenite also induced cell cycle arrest and apoptosis. The cell cycle arrest involved the down-regulation of cyclin A2, cyclin D1, cyclin E, cyclin dependent kinases (CDK) 2, CDK4, and CDK6. Apoptosis involved downregulation of anti-apoptotic proteins Bcl-2, Bcl-xL, survivin, and inhibitor of apoptosis protein (IAP) and up-regulation of pro-apoptotic protein Bax. Taken together, our results suggest that a possible mechanism of arsenite-induced toxicity under low/no GSH conditions, is to negatively regulate GCS-2 cell proliferation by attenuating Akt and AP-1 by ubiquitination and causing cell cycle dysfunction and apoptosis.

show abstract

Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding

Cited by 62 publications

References 65 publications

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

Genome-Wide Identification of Molecular Pathways and Biomarkers in Response to Arsenic Exposure in Zebrafish Liver

Differential activation of AP‐1 in human bladder epithelial cells by inorganic and methylated arsenicals

Arsenite causes down‐regulation of Akt and c‐Fos, cell cycle dysfunction and apoptosis in glutathione‐deficient cells

Contact Info

Product

Resources

About