Alterations in the Growth Factor Signal Transduction Pathways and Modulators of the Cell Cycle in Endocervical Cells from Macaques Exposed to TCDD

Enan, Essam; El-Sabeawy, Faten; Scott, M. A.; Overstreet, James W.; Lasley, Bill L.

doi:10.1006/taap.1998.8470

Cited by 37 publications

(22 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ERK phosphorylation in response to TCDD has been demonstrated in primary cultures of endocervical epithelium of macaque, and in Jurkat and mouse hepatoma cells (Enan et al, 1998b;Tan et al, 2002;Kwon et al, 2003). Our data showed that activation of ERK was required in TNF-α expression triggered by TCDD: Phosphorylation of ERK in differentiated THP-1 macrophages was induced within 30 min of TCDD treatment, and PD98059, an inhibitor of the MEK-ERK pathway, abolished TCDD-induced TNF-α expression.…”

Section: Discussionmentioning

confidence: 50%

Signaling pathway for 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced TNF-α production in differentiated THP-1 human macrophages

Cheon

Woo²,

Lee³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

Abstract2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototypic halogenated aromatic hydrocarbon (HAH), is known as one of the most potent toxicants. At least a part of its toxic effects appears to be derived from its ability to induce TNF-α production. However, the signaling pathway of TCDD that leads to TNF-α expression has not been elucidated. In this study, we investigated the signaling mechanism of TCDD-induced TNF-α expression in PMA-differentiated THP-1 macrophages. TCDD induced both mRNA and protein expression of TNF-α in a dose-and time-dependent manner. α-Naphthoflavone (NF), an aryl hydrocarbon receptor (AhR) inhibitor, prevented the TCDD-induced expression of TNF-α at both mRNA and protein levels. Genistein, a protein tyrosine kinase (PTK) inhibitor, and PD153035, an EGFR inhibitor, also blocked the increase of TNF-α expression by TCDD, indicating the role of EGFR in TCDD-induced TNF-α expression. On the other hand, PP2, a c-Src specific inhibitor, did not affect TCDD-induced TNF-α expression. EGFR phosphorylation was detected as early as 5 min after TCDD treatment. TCDD-induced EGFR activation was AhR-dependent since co-treatment with α-NF prevented it. ERK was found to be a downstream effector of EGFR activation in the signaling pathway leading to TNF-α production after TCDD stimulation. Activation of ERK was observed from 30 min after TCDD treatment. PD98059, an inhibitor of the MEK-ERK pathway, completely prevented the TNF-α mRNA and protein expression induced by TCDD, whereas inhibitors of JNK and p38 MAPK had no effect. PD153035, an EGFR inhibitor, as well as α-NF significantly reduced ERK phosphorylation, suggesting that ERK activation by TCDD was mediated by both EGFR and AhR. These results indicate that TNF-α production by TCDD in differentiated THP-1 macrophages is AhR-dependent and involves activation of EGFR and ERK, but not c-Src, JNK, nor p38 MAPK. A signaling pathway is proposed where TCDD induces sequential activation of AhR, EGFR and ERK, leading to the increased expression of TNF-α.

show abstract

Section: Discussionmentioning

confidence: 50%

Signaling pathway for 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced TNF-α production in differentiated THP-1 human macrophages

Cheon

Woo²,

Lee³

et al. 2007

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…2). Growth factor activation through the "classical" AhR ligand TCDD was observed earlier in keratinocytes (42), cervical cells from macaques (43) and in rat liver epithelial cells (22). In the two latter studies, the tyrosine kinase c-src was found to be responsible for the observed growth factor receptor activation after ligand binding to the AhR complex.…”

Section: Discussionmentioning

confidence: 74%

Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation

Fritsche

Schäfer

Calles

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

404

405

View full text Add to dashboard Cite

UVB radiation-induced signaling in mammalian cells involves two major pathways: one that is initiated through the generation of DNA photoproducts in the nucleus and a second one that occurs independently of DNA damage and is characterized by cell surface receptor activation. The chromophore for the latter one has been unknown. Here, we report that the UVB response involves tryptophan as a chromophore. We show that through the intracellular generation of photoproducts, such as the arylhydrocarbon receptor (

show abstract

“…These patterns were disrupted by TCDD treatment (ANOVA p Ͻ 0.05) with peaks being truncated by nearly 50%. The cyclin-dependent kinase inhibitors p21 and p27 also have been demonstrated to be both TCDDresponsive and regulated with circadian rhythmicity (Enan et al, 1998;Bjarnason et al, 1999;Kolluri et al, 1999;Cheng et al, 2000). However, analysis of their mRNA expression over 24 h revealed only modest rhythmicity in Lin Ϫ Sca-1 ϩ cells and no changes with TCDD exposure (data not shown).…”

Section: Tcdd Disrupts the Circadian Rhythm Of Linmentioning

confidence: 95%

The Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin Alters the Circadian Rhythms, Quiescence, and Expression of Clock Genes in Murine Hematopoietic Stem and Progenitor Cells

Garrett

Gasiewicz

2006

Mol Pharmacol

View full text Add to dashboard Cite

2,3,7,, an aryl hydrocarbon receptor (AhR) agonist, has been identified as a potent immunohematopoietic toxicant with the ability to alter the number of Lin Ϫ Sca-1 ϩ cKit ϩ (LSK) bone marrow cells, a population enriched for murine hematopoietic stem cells. The biology of these cells is governed by circadian rhythms and TCDD has been shown to disrupt circadian rhythms of other biological endpoints. We investigated the effect of TCDD on the circadian rhythms of hematopoietic precursors. Female C57BL/6 mice were treated with a single oral dose of 10 g/kg TCDD. Five days later, bone marrow was harvested every 4 h for 24 h and stained for specific hematopoietic populations using fluorescently labeled antibodies. In addition, cells were placed into semisolid culture to measure different functionally defined populations. Activation of the AhR by TCDD elicited disruptions in the rhythms of LSK cell numbers and phenotypically defined myeloid and erythroid precursors. Simultaneous DNA and RNA staining revealed an abnormal in vivo rhythm of percentage of total number of LSK cells in G 0 phase of the cell cycle, suggesting disruption of stem cell quiescence. Finally, quantitative reverse transcription-polymerase chain reaction revealed that expression of AhR and Arnt mRNA within enriched hematopoietic precursors oscillates with a circadian period. Modest changes in the 24-h expression of mPer1 and mPer2 mRNA and increased AhR repressor mRNA after TCDD exposure suggest a direct effect on the molecular machinery responsible for these rhythms. Together, these data demonstrate that activation of the AhR by TCDD disrupts the circadian rhythms associated with murine hematopoietic precursors.

show abstract

Alterations in the Growth Factor Signal Transduction Pathways and Modulators of the Cell Cycle in Endocervical Cells from Macaques Exposed to TCDD

Cited by 37 publications

References 60 publications

Signaling pathway for 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced TNF-α production in differentiated THP-1 human macrophages

Signaling pathway for 2,3,7,8-tetrachlorodibenzo- p-dioxin-induced TNF-α production in differentiated THP-1 human macrophages

Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation

The Aryl Hydrocarbon Receptor Agonist 2,3,7,8-Tetrachlorodibenzo-p-dioxin Alters the Circadian Rhythms, Quiescence, and Expression of Clock Genes in Murine Hematopoietic Stem and Progenitor Cells

Contact Info

Product

Resources

About