Platonova Natalia, Guolikhandanova Natalie, Tsymbalenko Nadezhda, Zhiguleva Evelyn, Zhivulko Tatiana, Vasin Andrey, Evsukova Inna, Puchkova Ludmila
Department of Molecular Genetics, Research Institute for Experimental Medicine, Pavlov Str, 12, 197376 St Petersburg, Russian Federation.
J Trace Elem Med Biol. 2007;21(3):184-93. doi: 10.1016/j.jtemb.2007.04.003. Epub 2007 Jul 12.
This research focuses on the role of milk ceruloplasmin (Cp), the main extracellular copper-containing protein of vertebrates, as a source of copper for newborns. In the first part of the study, Cp concentration and Cp-associated copper were measured in human skimmed milk at the 1st and the 5th days postpartum. It was shown that most of the copper was associated with Cp and that the decrease in copper concentration during lactation was related to the drop of Cp levels. The following in vivo experiments demonstrated that milk [(125)I]Cp per os administered to 6-day-old rats (embryonic-type copper metabolism) was transported into their bloodstream. The electrophoretic mobility and relative molecular weight of [(125)I]Cp transferred through the cellular barrier remained unaltered. However, 22-day-old rats (adult-type copper metabolism) digested the administered milk [(125)I]Cp completely. In the final part of the study, newborn rats were fed with baby formula for 8d. It was found that these rats switched their copper metabolism from embryonic type to adult type earlier than their littermates fed by dams. Activation of Cp gene expression in the liver, increased Cp and copper concentrations in the blood, and reduced copper content of the liver were observed in the rats fed with baby formula. In the brain, no copper concentration change was observed, but Cp and copper concentrations were dramatically increased in the cerebrospinal fluid. The role of milk Cp as a source of copper adapted to embryonic-type copper metabolism is discussed.
本研究聚焦于乳铜蓝蛋白(Cp)这一脊椎动物主要的细胞外含铜蛋白作为新生儿铜来源的作用。在研究的第一部分,测定了产后第1天和第5天的人脱脂乳中Cp浓度及与Cp相关的铜含量。结果表明,大部分铜与Cp相关,且哺乳期铜浓度的降低与Cp水平的下降有关。接下来的体内实验表明,给6日龄大鼠(胚胎型铜代谢)经口灌胃乳[(125)I]Cp后,其被转运至血液中。穿过细胞屏障的[(125)I]Cp的电泳迁移率和相对分子量未发生改变。然而,22日龄大鼠(成年型铜代谢)则将灌胃的乳[(125)I]Cp完全消化。在研究的最后部分,给新生大鼠喂食婴儿配方奶粉8天。结果发现,这些大鼠比由母鼠哺乳的同窝大鼠更早地将其铜代谢从胚胎型转变为成年型。在喂食婴儿配方奶粉的大鼠中,观察到肝脏中Cp基因表达激活、血液中Cp和铜浓度升高以及肝脏铜含量降低。在大脑中,未观察到铜浓度变化,但脑脊液中Cp和铜浓度显著升高。本文讨论了乳Cp作为适应胚胎型铜代谢的铜来源的作用。