کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5845988 | 1128439 | 2015 | 17 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions
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کلمات کلیدی
qPCRXAV939T-cell factor/lymphoid enhancer-binding factorPCNAAZPDLCsZGA6-formylindolo[3,2-b]carbazole3-methylcholanthreneAHR2PCB126FICZGSK3βCYP1TCDDAHRDPFhpfAPC2,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسین3,3′,4,4′,5-pentachlorobiphenyl - 3،3 '، 4،4'، 5-پنتاکلروبوفنیلDMSO - DMSO3-MC - MC-3quantitative real-time RT-PCR - RT-PCR زمان واقعی کمadenomatosis polyposis coli - آدنوماتوز پولیپوز کولیProliferating Cell Nuclear Antigen - آنتیژن هسته ای تکثیر سلولیbeta-catenin - بتا کاتینینDioxin-like compounds - ترکیبات دیوکسین مانندZebrafish embryo - جنین ZebrafishDimethyl sulfoxide - دیمتیل سولفواکسیدdays post-fertilization - روز پس از لقاحhours post-fertilization - ساعت پس از لقاحzygotic genome activation - فعال سازی ژنوم زگوتاmorpholino - مورفولینوGlycogen synthase kinase 3β - گلیکوزین سنتاز کیناز 3βaryl hydrocarbon receptor - گیرنده آرویل هیدروکربن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions Combination effects of AHR agonists and Wnt/β-catenin modulators in zebrafish embryos: Implications for physiological and toxicological AHR functions](/preview/png/5845988.png)
چکیده انگلیسی
Wnt/β-catenin signaling regulates essential biological functions and acts in developmental toxicity of some chemicals. The aryl hydrocarbon receptor (AHR) is well-known to mediate developmental toxicity of persistent dioxin-like compounds (DLCs). Recent studies indicate a crosstalk between β-catenin and the AHR in some tissues. However the nature of this crosstalk in embryos is poorly known. We observed that zebrafish embryos exposed to the β-catenin inhibitor XAV939 display effects phenocopying those of the dioxin-like 3,3â²,4,4â²,5-pentachlorobiphenyl (PCB126). This led us to investigate the AHR interaction with β-catenin during development and ask whether developmental toxicity of DLCs involves antagonism of β-catenin signaling. We examined phenotypes and transcriptional responses in zebrafish embryos exposed to XAV939 or to a β-catenin activator, 1-azakenpaullone, alone or with AHR agonists, either PCB126 or 6-formylindolo[3,2-b]carbazole (FICZ). Alone 1-azakenpaullone and XAV939 both were embryo-toxic, and we found that in the presence of FICZ, the toxicity of 1-azakenpaullone decreased while the toxicity of XAV939 increased. This rescue of 1-azakenpaullone effects occurred in the time window of Ahr2-mediated toxicity and was reversed by morpholino-oligonucleotide knockdown of Ahr2. Regarding PCB126, addition of either 1-azakenpaullone or XAV939 led to lower mortality than with PCB126 alone but surviving embryos showed severe edemas. 1-Azakenpaullone induced transcription of β-catenin-associated genes, while PCB126 and FICZ blocked this induction. The data indicate a stage-dependent antagonism of β-catenin by Ahr2 in zebrafish embryos. We propose that the AHR has a physiological role in regulating β-catenin during development, and that this is one point of intersection linking toxicological and physiological AHR-governed processes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 284, Issue 2, 15 April 2015, Pages 163-179
Journal: Toxicology and Applied Pharmacology - Volume 284, Issue 2, 15 April 2015, Pages 163-179
نویسندگان
Emma Wincent, John J. Stegeman, Maria E. Jönsson,