| Neural precursor cell proliferation is disrupted through activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin. | |
| | |
MedLine Citation:
|
PMID: 20486776 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Neurogenesis involves the proliferation of multipotent neuroepithelial stem cells followed by differentiation into lineage-restricted neural precursor cells (NPCs) during the embryonic period. Interestingly, these progenitor cells express robust levels of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates expression of genes important for growth regulation, and xenobiotic metabolism. Upon binding 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a pervasive environmental contaminant and potent AhR ligand, AhR, is activated and disrupts gene expression patterns to produce cellular toxicity. Because of its widespread distribution in the brain during critical proliferative phases of neurogenesis, it is conceivable that AhR participates in NPC expansion. Therefore, this study tested the hypothesis that AhR activation by TCDD disrupts signaling events that regulate NPC proliferation. The C17.2 NPC line served as a model system to (1) assess whether NPCs are targets for TCDD-induced neurotoxicity and (2) characterize the effects of TCDD on NPC proliferation. We demonstrated that C17.2 NPCs express an intact AhR signaling pathway that becomes transcriptionally active after TCDD exposure. (3)H-thymidine and alamar blue reduction assays indicated that TCDD suppresses NPC proliferation in a concentration-dependent manner without the loss of cell viability. Cell cycle distribution analysis by flow cytometry revealed that TCDD-induced growth arrest results from an impaired G1 to S cell cycle transition. Moreover, TCDD exposure altered p27( kip1) and cyclin D1 cell cycle regulatory protein expression levels consistent with a G1 phase arrest. Initial studies in primary NPCs isolated from the ventral forebrain of embryonic mice demonstrated that TCDD reduced cell proliferation through a G1 phase arrest, corroborating our findings in the C17.2 cell line. Together, these observations suggest that the inappropriate or sustained activation of AhR by TCDD during neurogenesis can interfere with signaling pathways that regulate neuroepithelial stem cell/NPC proliferation, which could adversely impact final cell number in the brain and lead to functional impairments. |
| | |
Authors:
|
Sarah E Latchney; Daniel T Lioy; Ellen C Henry; Thomas A Gasiewicz; Frederick G Strathmann; Margot Mayer-Pröschel; Lisa A Opanashuk |
Related Documents
:
|
3319436 - Effects of glycyl-histidyl-lysine on morris hepatoma 7777 cells. 1534666 - Cell proliferation and control. 4044676 - Consequences of parental exposure to serum-free medium for progeny cell division. 8759936 - Zinc deficiency affects cell cycle and deoxythymidine kinase gene expression in hut-78 ... 22787086 - Mutant p53 alleles can be restored to the wild-type conformation. 11234996 - Iron-induced oxidative damage in colon carcinoma (caco-2) cells. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-31 |
Journal Detail:
|
Title: Stem cells and development Volume: 20 ISSN: 1557-8534 ISO Abbreviation: Stem Cells Dev. Publication Date: 2011 Feb |
Date Detail:
|
Created Date: 2011-01-24 Completed Date: 2011-06-24 Revised Date: 2012-02-01 |
Medline Journal Info:
|
Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: United States |
Other Details:
|
Languages: eng Pagination: 313-26 Citation Subset: IM |
Affiliation:
|
Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cell Cycle / drug effects Cell Cycle Proteins / genetics, metabolism Cell Proliferation / drug effects* Cell Survival / drug effects Cells, Cultured DNA Replication / drug effects Embryo, Mammalian Female Gene Expression Regulation, Developmental / drug effects Male Mice Mice, Inbred C57BL Mitogens / pharmacology Neural Stem Cells / cytology, drug effects* Neurogenesis Neurons / cytology, drug effects* Pregnancy Prosencephalon / cytology Receptors, Aryl Hydrocarbon / agonists*, metabolism Tetrachlorodibenzodioxin / pharmacology* Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
|
P30 ES01247/ES/NIEHS NIH HHS; R01 ES016357/ES/NIEHS NIH HHS; R21 ES013512/ES/NIEHS NIH HHS; T32 ES07026/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cell Cycle Proteins; 0/Mitogens; 0/Receptors, Aryl Hydrocarbon; 1746-01-6/Tetrachlorodibenzodioxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Bone morphogenetic protein 4 mediates human embryonic germ cell derivation.
Next Document: Human bone marrow and adipose tissue mesenchymal stem cells: a user's guide.