Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development

Hdl Handle:
http://hdl.handle.net/10675.2/635
Title:
Prenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial development
Authors:
Wang, G; Bieberich, Erhard
Abstract:
Fetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-b1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.
Citation:
Cell Death Dis. 2010 May 27; 1(5):e46
Issue Date:
27-May-2010
URI:
http://hdl.handle.net/10675.2/635
DOI:
10.1038/cddis.2010.22
PubMed ID:
21364652
PubMed Central ID:
PMC3032308
Type:
Article
ISSN:
2041-4889
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Gen_US
dc.contributor.authorBieberich, Erharden_US
dc.date.accessioned2012-10-26T16:26:57Z-
dc.date.available2012-10-26T16:26:57Z-
dc.date.issued2010-05-27en_US
dc.identifier.citationCell Death Dis. 2010 May 27; 1(5):e46en_US
dc.identifier.issn2041-4889en_US
dc.identifier.pmid21364652en_US
dc.identifier.doi10.1038/cddis.2010.22en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/635-
dc.description.abstractFetal alcohol syndrome (FAS) is caused by maternal alcohol consumption during pregnancy. The reason why specific embryonic tissues are sensitive toward ethanol is not understood. We found that in neural crest-derived cell (NCC) cultures from the first branchial arch of E10 mouse embryos, incubation with ethanol increases the number of apoptotic cells by fivefold. Apoptotic cells stain intensely for ceramide, suggesting that ceramide-induced apoptosis mediates ethanol damage to NCCs. Apoptosis is reduced by incubation with CDP-choline (citicoline), a precursor for the conversion of ceramide to sphingomyelin. Consistent with NCC cultures, ethanol intubation of pregnant mice results in ceramide elevation and increased apoptosis of NCCs in vivo. Ethanol also increases the protein level of prostate apoptosis response 4 (PAR-4), a sensitizer to ceramide-induced apoptosis. Prenatal ethanol exposure is concurrent with malformation of parietal bones in 20% of embryos at day E18. Meninges, a tissue complex derived from NCCs, is disrupted and generates reduced levels of TGF-b1, a growth factor critical for bone and brain development. Ethanol-induced apoptosis of NCCs leading to defects in the meninges may explain the simultaneous presence of cranial bone malformation and cognitive retardation in FAS. In addition, our data suggest that treatment with CDP-choline may alleviate the tissue damage caused by alcohol.en_US
dc.rightsCopyright © 2010 Macmillan Publishers Limiteden_US
dc.subjectOriginal Articleen_US
dc.titlePrenatal alcohol exposure triggers ceramide-induced apoptosis in neural crest-derived tissues concurrent with defective cranial developmenten_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3032308en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.