Alcohol-mediated calcium signals dysregulate pro-survival Snai2/PUMA/Bcl2 networks to promote p53-mediated apoptosis in avian neural crest progenitors.

ABSTRACT: BACKGROUND:Prenatal alcohol exposure causes distinctive craniofacial anomalies that arise, in part, from the apoptotic elimination of neural crest (NC) progenitors that form the face. This vulnerability of NC to alcohol is puzzling as they normally express the transcriptional repressor Snail1/2 (in chick Snai2), which suppresses apoptosis and promotes their migration. Here, we investigate alcohol's impact upon Snai2 function. METHODS:Chick cranial NC cells were treated with acute alcohol (52?mM, 2 hr). We evaluated NC migration, gene expression, proliferation, and apoptosis thereafter. RESULTS:Transient alcohol exposure induced Snai2 (191%?±?23%; p?=?.003) and stimulated NC migration (p?=?.0092). An alcohol-induced calcium transient mediated this Snai2 induction, and BAPTA-AM blocked whereas ionomycin mimicked these pro-migratory effects. Alcohol suppressed CyclinD1 protein content (59.1?±?12%, p?=?.007) and NC proliferation (19.7?±?5.8%, p?

SUBMITTER: Flentke GR 

PROVIDER: S-EPMC7017393 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature