Niculescu Mihai D, Wu Renan, Guo Zhong, da Costa Kerry Ann, Zeisel Steven H
Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599-7461, USA.
Toxicol Sci. 2007 Apr;96(2):321-6. doi: 10.1093/toxsci/kfl200. Epub 2007 Jan 4.
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.
二乙醇胺（DEA）是许多消费品和众多工业应用中广泛使用的一种成分。此前有报道称，对小鼠进行DEA皮肤给药会减少肝脏中的胆碱储备，并改变胎儿的大脑发育。本研究的目的是利用小鼠神经前体细胞在体外评估DEA作用的潜在机制。暴露于DEA处理（3mM）的细胞在48小时时增殖较少（通过5-溴-2-脱氧尿苷掺入法，为对照[CT]的24%）, 并且在72小时时细胞凋亡增加（为CT的308%）。DEA处理会使细胞对胆碱的摄取减少（至CT的52%），导致细胞内胆碱和磷酸胆碱的浓度降低（分别为CT的55%和12%）。当生长培养基中的胆碱浓度增加三倍（至210μM）时，DEA暴露对细胞增殖和凋亡的影响得到了预防，然而细胞内磷酸胆碱的浓度仍然较低。在胆碱激酶测定中, 我们观察到DEA可以磷酸化为磷酸DEA，代价是胆碱。因此, DEA的作用可能是通过抑制胆碱转运进入神经前体细胞以及改变胆碱的代谢来介导的。我们的研究表明，产前暴露于DEA可能会对大脑发育产生不利影响。
