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通过数学建模估计不同酶在HO中和及细胞辐射抗性中的作用。

Role of Different Enzymes in HO Neutralization and Cellular Radioresistance, Estimated by Mathematical Modeling.

作者信息

Ciesielska Sylwia, Mazur Krzysztof, Fujarewicz Krzysztof, Rzeszowska-Wolny Joanna

机构信息

Department of Systems Biology and Engineering, Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, 44-100 Gliwice, Poland.

Biotechnology Centre, Silesian University of Technology, 44-100 Gliwice, Poland.

出版信息

Int J Mol Sci. 2025 Aug 11;26(16):7754. doi: 10.3390/ijms26167754.

DOI:10.3390/ijms26167754
PMID:40869074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12386452/
Abstract

Reactive oxygen species (ROS) are fundamental components found in cells that exist in an oxygen environment. While they are often viewed as detrimental metabolic byproducts that can harm cells, leading to aging and cell death, they can also play a role in cellular regulatory processes and have beneficial effects. One of the main ROS present in all cells is hydrogen peroxide (HO), which can function as a signaling molecule in extra- and intracellular signaling. To enhance our understanding of how various enzymes regulate cellular HO levels, we created a mathematical model of HO neutralization and performed computer simulations to estimate the neutralization efficiency in various types of cells. Data on gene expression for genes participating in this process were incorporated into the calculations, along with the regulation of enzymes in oxidation and reduction processes. The conducted simulations demonstrate that cells originating from different tissues utilize systems neutralizing HO variously, which results in differences in HO cellular levels. The simulation findings suggest that the differences in radiosensitivity seen in various cancer cell types may be linked to their effectiveness in scavenging HO. Analysis of results from model simulations for colorectal, lung, and breast cancer cell lines indicated that radiosensitive cell lines exhibited elevated levels of HO, attributed to the reduced efficiency of neutralizing enzymes. By highlighting cell-type-specific differences in HO neutralization, our findings may contribute to a deeper understanding of redox regulation in cancer cells and reveal new potential correlations with radioresistance.

摘要

活性氧(ROS)是存在于有氧环境中的细胞中的基本成分。虽然它们通常被视为会损害细胞、导致衰老和细胞死亡的有害代谢副产物,但它们也可在细胞调节过程中发挥作用并产生有益影响。所有细胞中存在的主要ROS之一是过氧化氢(HO),它可在细胞外和细胞内信号传导中充当信号分子。为了加深我们对各种酶如何调节细胞HO水平的理解,我们创建了一个HO中和的数学模型,并进行了计算机模拟以估计各种类型细胞中的中和效率。参与此过程的基因的基因表达数据以及氧化和还原过程中酶的调节被纳入计算。进行的模拟表明,源自不同组织的细胞以不同方式利用中和HO的系统,这导致细胞内HO水平存在差异。模拟结果表明,在各种癌细胞类型中看到的放射敏感性差异可能与其清除HO的有效性有关。对结肠直肠癌、肺癌和乳腺癌细胞系的模型模拟结果分析表明,放射敏感细胞系的HO水平升高,这归因于中和酶效率的降低。通过突出HO中和中细胞类型特异性差异,我们的发现可能有助于更深入地了解癌细胞中的氧化还原调节,并揭示与放射抗性的新潜在相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/39a6/12386452/eb4593584c7b/ijms-26-07754-g005.jpg
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