Gerasimenko T N, Senyavina N V, Anisimov N U, Tonevitskaya S A
BioCilicum Research and Production Center, Moscow, Russia.
Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
Bull Exp Biol Med. 2016 May;161(1):187-92. doi: 10.1007/s10517-016-3373-7. Epub 2016 Jun 4.
We created a physiologically substantiated kinetic model of cadmium transport and toxicity in intestinal cell model (Caco-2 cells). Transcriptome profiling of Caco-2 cells revealed high content of transporter DMT1 and ZIP14 and intensive expression of some calcium channels of the CACN family. The mathematical model describing three types of transporters, as well as intracellular cadmium binding with metallothionein and excretion through the basolateral membrane allowed us to construct cadmium uptake and transport curves that approximated the previously obtained experimental data. Using the proposed model, we determined toxic intracellular cadmium concentration leading to cell death and impairing the integrity of cell monolayer and described cadmium transport in this case.
我们在肠道细胞模型(Caco-2细胞)中创建了一个有生理学依据的镉转运和毒性动力学模型。Caco-2细胞的转录组分析显示,转运蛋白DMT1和ZIP14含量高,且CACN家族的一些钙通道表达强烈。描述三种转运蛋白类型以及细胞内镉与金属硫蛋白结合并通过基底外侧膜排泄的数学模型,使我们能够构建镉摄取和转运曲线,这些曲线与先前获得的实验数据相近。使用所提出的模型,我们确定了导致细胞死亡并损害细胞单层完整性的细胞内有毒镉浓度,并描述了这种情况下的镉转运。