title: Involvement of seven in absentia homolog-1 in ethanol-induced apoptosis in neural crest cells.
abstract: Ethanol-induced apoptosis in selected cell populations is a major component of pathogenesis underlying ethanol-induced teratogenesis. However, there is a fundamental gap in understanding how ethanol leads to apoptosis in embryos. In this study, we investigate the role of seven in absentia homolog-1 (Siah1) protein, an E3 ubiquitin ligase, in ethanol-induced apoptosis. Using an in vitro model of neural crest cell (NCC), JoMa1.3 cells, we found that exposure to 100mM ethanol resulted in a significant increase in Siah1 mRNA expression in NCCs, an ethanol-sensitive cell population implicated in Fetal Alcohol Spectrum Disorders (FASD). Treatment with 100mM ethanol for 24h also significantly increased the protein expression of Siah1 in JoMa1.3 cells. The nuclear translocation and accumulation of Siah1 was evidenced in the cells exposed to ethanol. In addition, we have found that the inhibition of Siah1 function with siRNA prevents ethanol-induced increase in Siah1 protein expression and nuclear translocation in NCCs. Down-regulation of Siah1 by siRNA also greatly diminished ethanol-induced cell death and caspase-3 activation, indicating that inhibition of Siah1 can attenuate ethanol-induced apoptosis. These results strongly suggest that Siah1 plays an important role in ethanol-induced apoptosis in NCCs.
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, United States.
authors.forename: Haijing
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, United States.
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, United States.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, United States.
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605, United States. Electronic address: sychen@uic.edu.
authors.forename: Shao-Yu
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000431:Ethanol / Q000633:toxicity*; D051379:Mice; D009432:Neural Crest / Q000187:drug effects* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000187:drug effects* / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000187:drug effects* / Q000235:genetics*; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D000431:Ethanol; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D053148:Caspase 3
keywords: Apoptosis; Ethanol; Fetal Alcohol Spectrum Disorders; Neural crest cells; Siah1