Induction of the Nrf2-driven antioxidant response by tert-butylhydroquinone prevents ethanol-induced apoptosis in cranial neural crest cells.
Previous studies have shown that ethanol exposure causes apoptosis in cranial neural crest cells (NCCs), an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). Additionally, induction of endogenous antioxidants through activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) has been shown to prevent oxidative stress and apoptosis in ethanol-exposed mouse embryos. The objective of this study was to test whether tert-butylhydroquinone (tBHQ), an Nrf2 inducer, can protect NCCs against ethanol-induced apoptosis. Ethanol exposure was shown to cause a moderate increase in the protein expression of Nrf2 and its downstream antioxidants in the NCCs. Treatment of NCCs with tBHQ alone significantly increased the protein expression of Nrf2 and its downstream antioxidants and also significantly increased the activities of the antioxidant enzymes. In NCCs exposed to ethanol, the tBHQ-mediated antioxidant response prevented oxidative stress and apoptosis. These results clearly demonstrate that the activation of Nrf2 signaling confers protection against ethanol-induced apoptosis in NCCs.
Yan
Dong
D
Bowles Center for Alcohol Studies & Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC 27599, USA. yandong@med.unc.edu
Dong
Jian
J
Sulik
Kathleen K
KK
Chen
Shao-yu
SY
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D006873:Hydroquinones / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D015398:Signal Transduction / Q000235:genetics
D000975:Antioxidants; D006873:Hydroquinones; D051267:NF-E2-Related Factor 2; D000431:Ethanol; C018855:2-tert-butylhydroquinone