title: Different regulation of aryl hydrocarbon receptor-regulated genes in response to dioxin in undifferentiated and neuronally differentiated human neuroblastoma SH-SY5Y cells.
abstract: Some environmental pollutants derived from industrial processes have been suggested to be responsible for neurological impairment in children, especially in heavily polluted areas. Since these compounds are usually activators of aryl hydrocarbon receptor (AhR), it would be important to better understand the molecular pathways downstream of AhR leading to neural deficits. To this purpose, appropriate in vitro human neural model is much needed. Here we have investigated whether undifferentiated and neuronally differentiated human neuroblastoma cells, SH-SY5Y cells, can provide a suitable model for monitoring AhR activity induced by environmental pollutants, focusing on 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), a known activator of AhR. Further characterization of differentiated SH-SY5Y showed an increase in AhRR (aryl hydrocarbon receptor repressor), no change in ARNT1 (AhR nuclear translocator 1), and a decrease in ARNT2 expression with differentiation; in contrast, AhR was undetectable in both undifferentiated and differentiated cells. Nonetheless, treatment of parental as well as differentiated SH-SY5Y cells with TCDD resulted in the induction of AhR-regulated genes, CYP1A1 and CYP1B1; AhRR expression was also affected, but to a much smaller extent. These results indicate that undifferentiated SH-SY5Y are less sensitive to TCDD than neuronally differentiated ones, suggesting a higher resistance of the undifferentiated tumor cells to toxic insults. They also suggest that TCDD in these cells may not act via direct activation of AhR that is undetectable in SH-SY5Y as well as in differentiated neurons. Hence, these cells do not provide an appropriate model for studying ligand-mediated activation of AhR.
authors.affiliation: a Department of Cell Biology and Genetics, Faculty of Science , Palacky University , Olomouc , Czech Republic and.
authors.forename: Saima
authors.initials: S
authors.lastname: Imran
authors.affiliation: b Stem Cells and Regenerative Medicine Section, UCL Institute of Child Health , London , UK.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferretti
authors.affiliation: a Department of Cell Biology and Genetics, Faculty of Science , Palacky University , Olomouc , Czech Republic and.
authors.forename: Radim
authors.initials: R
authors.lastname: Vrzal
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008024:Ligands; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D061251:Primary Cell Culture; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*
chemical_list: D016895:Culture Media, Serum-Free; D004785:Environmental Pollutants; D008024:Ligands; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon
keywords: ARNT2; AhR; AhRR; CYP1A1; CYP1B1