2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits neurite outgrowth in differentiating human SH-SY5Y neuroblastoma cells.
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), a highly toxic environmental pollutant, is known to induce neurodevelopmental and neurobehavioral deficits. However, the underlying mechanism of TCDD-mediated neurotoxicity has remained unclear. We have studied TCDD inhibition of neurite outgrowth using human SH-SY5Y neuroblastoma cells induced to differentiate by all-trans-retinoic acid (RA). TCDD, at concentrations of 3 nM or 5 nM, had no significant effect on the viability of either undifferentiating or differentiated SH-SY5Y cells. However, differentiating SH-SY5Y cells exhibited a distinct decrease of neurite outgrowth 48 h after TCDD treatment in a dose-dependent manner. TCDD treatment 12h or 24h after RA stimulation did not elicit a significant inhibition of neurite outgrowth, whereas TCDD cotreatment with RA or TCDD treatment at 6h after RA stimulation significantly inhibited neurite outgrowth. Western blot analysis of cell extracts of RA-stimulated differentiating SH-SY5Y cells showed increased level of cross reactivities with tissue glutaminase (TGase) antibody compared to control extracts, in a time-dependent manner. By contrast, treatment of differentiating SH-SY5Y cells with 1-5 nM TCDD resulted in decreased level of cross-reactivities with TGase antibody in a dose-dependent manner. The results indicate that TCDD is able to inhibit neurite outgrowth by differentiating SH-SY5Y cells and that this effect might result from reduced levels of TGase.
Jung
Jee Eun
JE
Department of Life Science, Kyonggi University, Suwon, Kyonggi-do 443-760, Republic of Korea.
Moon
Jun Yeon
JY
Ghil
Sung Ho
SH
Yoo
Byung Sun
BS
D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008858:Microscopy, Phase-Contrast; D016501:Neurites / Q000187:drug effects* / Q000648:ultrastructure; D009447:Neuroblastoma; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011503:Transglutaminases / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D014212:Tretinoin; D011503:Transglutaminases