Ochratoxin A at nanomolar concentration perturbs the homeostasis of neural stem cells in highly differentiated but not in immature three-dimensional brain cell cultures.

Détails

ID Serval
serval:BIB_FB2B373ECF67
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Ochratoxin A at nanomolar concentration perturbs the homeostasis of neural stem cells in highly differentiated but not in immature three-dimensional brain cell cultures.
Périodique
Toxicology Letters
Auteur⸱e⸱s
Zurich M.G., Honegger P.
ISSN
1879-3169 (Electronic)
ISSN-L
0378-4274
Statut éditorial
Publié
Date de publication
2011
Volume
205
Numéro
2
Pages
203-208
Langue
anglais
Résumé
Ochratoxin A (OTA), a fungal contaminant of basic food commodities, is known to be highly cytotoxic, but the pathways underlying adverse effects at subcytotoxic concentrations remain to be elucidated. Recent reports indicate that OTA affects cell cycle regulation. Therefore, 3D brain cell cultures were used to study OTA effects on mitotically active neural stem/progenitor cells, comparing highly differentiated cultures with their immature counterparts. Changes in the rate of DNA synthesis were related to early changes in the mRNA expression of neural stem/progenitor cell markers. OTA at 10nM, a concentration below the cytotoxic level, was ineffective in immature cultures, whereas in mature cultures it significantly decreased the rate of DNA synthesis together with the mRNA expression of key transcriptional regulators such as Sox2, Mash1, Hes5, and Gli1; the cell cycle activator cyclin D2; the phenotypic markers nestin, doublecortin, and PDGFRα. These effects were largely prevented by Sonic hedgehog (Shh) peptide (500ngml(-1)) administration, indicating that OTA impaired the Shh pathway and the Sox2 regulatory transcription factor critical for stem cell self-renewal. Similar adverse effects of OTA in vivo might perturb the regulation of stem cell proliferation in the adult brain and in other organs exhibiting homeostatic and/or regenerative cell proliferation.
Mots-clé
Animals, Cell Culture Techniques, Cell Differentiation/drug effects, Cell Proliferation/drug effects, Culture Media, Serum-Free, DNA/biosynthesis, Dose-Response Relationship, Drug, Homeostasis/drug effects, Neural Stem Cells/cytology, Neural Stem Cells/drug effects, Ochratoxins/toxicity, RNA, Messenger/metabolism, Rats, Reverse Transcriptase Polymerase Chain Reaction, Telencephalon/cytology, Telencephalon/drug effects, Transcription Factors/metabolism
Pubmed
Web of science
Création de la notice
05/09/2011 8:32
Dernière modification de la notice
20/08/2019 16:26
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