Skakauskas Vladas, Katauskis Pranas
Faculty of Mathematics and Informatics, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania.
Faculty of Mathematics and Informatics, Vilnius University, Naugarduko 24, 03225 Vilnius, Lithuania.
Comput Biol Chem. 2017 Aug;69:87-95. doi: 10.1016/j.compbiolchem.2017.05.009. Epub 2017 May 31.
We present a rather generic model for toxin (ricin) inhibition of protein biosynthesis in eukaryotic cells. We also study reduction of the ricin toxic effects with application of antibodies against the RTB subunit of ricin molecules. Both species initially are delivered extracellularly. The model accounts for the pinocytotic and receptor-mediated toxin endocytosis and the intact toxin exocytotic removal out of the cell. The model also includes the lysosomal toxin destruction, the intact toxin motion to the endoplasmic reticulum (ER) for separation of its molecules into the RTA and RTB subunits, and the RTA chain translocation into the cytosol. In the cytosol, one portion of the RTA undergoes degradation via the ERAD. The other its portion can inactivate ribosomes at a large rate. The model is based on a system of deterministic ODEs. The influence of the kinetic parameters on the protein concentration and antibody protection factor is studied in detail.
我们提出了一种相当通用的模型，用于描述毒素（蓖麻毒素）对真核细胞中蛋白质生物合成的抑制作用。我们还研究了应用针对蓖麻毒素分子RTB亚基的抗体来降低蓖麻毒素的毒性作用。这两种物质最初都是在细胞外递送的。该模型考虑了胞饮作用和受体介导的毒素内吞作用，以及完整毒素通过胞吐作用排出细胞的过程。该模型还包括溶酶体对毒素的破坏、完整毒素向内质网（ER）的移动以将其分子分离为RTA和RTB亚基，以及RTA链向内质网腔的转运。在内质网腔中，一部分RTA通过内质网相关蛋白降解（ERAD）途径发生降解。其另一部分则可以大量灭活核糖体。该模型基于一个确定性常微分方程系统。详细研究了动力学参数对蛋白质浓度和抗体保护因子的影响。
