title: Diethanolamine alters proliferation and choline metabolism in mouse neural precursor cells.
abstract: Diethanolamine (DEA) is a widely used ingredient in many consumer products and in a number of industrial applications. It has been previously reported that dermal administration of DEA to mice diminished hepatic stores of choline and altered brain development in the fetus. The aim of this study was to use mouse neural precursor cells in vitro to assess the mechanism underlying the effects of DEA. Cells exposed to DEA treatment (3mM) proliferated less (by 5-bromo-2-deoxyuridine incorporation) at 48 h (24% of control [CT]), and had increased apoptosis at 72 h (308% of CT). Uptake of choline into cells was reduced by DEA treatment (to 52% of CT), resulting in diminished intracellular concentrations of choline and phosphocholine (55 and 12% of CT, respectively). When choline concentration in the growth medium was increased threefold (to 210 microM), the effects of DEA exposure on cell proliferation and apoptosis were prevented, however, intracellular phosphocholine concentrations remained low. In choline kinase assays, we observed that DEA can be phosphorylated to phospho-DEA at the expense of choline. Thus, the effects of DEA are likely mediated by inhibition of choline transport into neural precursor cells and by altered metabolism of choline. Our study suggests that prenatal exposure to DEA may have a detrimental effect on brain development.
authors.affiliation: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7461, USA.
authors.forename: Mihai D
authors.initials: MD
authors.lastname: Niculescu
authors.forename: Renan
authors.initials: R
authors.lastname: Wu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Guo
authors.forename: Kerry Ann
authors.initials: KA
authors.lastname: da Costa
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002250:Carbon Radioisotopes; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002794:Choline / Q000378:metabolism* / Q000493:pharmacokinetics; D002797:Choline Kinase / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000378:metabolism / Q000633:toxicity*; D005260:Female; D020287:In Situ Nick-End Labeling; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010767:Phosphorylcholine / Q000378:metabolism; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D004983:Ethanolamines; D010767:Phosphorylcholine; C020283:diethanolamine; D002797:Choline Kinase; D001973:Bromodeoxyuridine; D002794:Choline