A Model of Cadmium Uptake and Transport in Caco-2 Cells.
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.
BioCilicum Research and Production Center, Moscow, Russia.
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Gerasimenko
BioCilicum Research and Production Center, Moscow, Russia. n.seniavina@bioclinicum.com.
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Senyavina
Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
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Anisimov
Moscow State University of Mechanical Engineering (MAMI), Moscow, Russia.
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Tonevitskaya
D001692:Biological Transport; D018938:Caco-2 Cells; D002104:Cadmium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D000099236:Solute Carrier Family 11, Member 2
D002104:Cadmium; D015220:Calcium Channels; D027682:Cation Transport Proteins; D000099236:Solute Carrier Family 11, Member 2; C497524:SLC39A14 protein, human
Caco-2; cadmium; model; permeability; toxicity