ROS and pentose phosphate pathway: mathematical modelling of the metabolic regulation in response to xenobiotic-induced oxidative stress and the proposed Impact of the gluconate shunt
ROS and pentose phosphate pathway: mathematical modelling of the metabolic regulation in response to xenobiotic-induced oxidative stress and the proposed Impact of the gluconate shunt
复制标题
ROS和磷酸戊糖途径：响应外源性诱导的氧化应激的代谢调节的数学模型以及葡萄糖酸分流的拟议影响
DOI：
10.1080/10715762.2019.1660777
复制
发表时间：
2019
影响因子：
3.3
通讯作者：
S. Schmitz-Spanke
中科院分区：
文献类型：
--
作者：
Schittenhelm;M. Neuss-Radu;N. Verma;M. Pink;S. Schmitz-Spanke
活性氧（ROS）的细胞内水平升高，例如由暴露于外源性物质引起，可引起严重的损伤。抗氧化防御机制涉及酶活性的调节，在一定程度上保护细胞。然而，持续或增加的暴露会使该系统不堪重负，导致不利的细胞状态。为了模拟暴露的情况下，并调查过渡到一个不利的细胞状态，一个数学模型的ROS的动态响应外源性诱导的氧化应激已经开发出来。它是基于人尿路上皮细胞（RT 4）暴露于硝化多环芳烃3-硝基苯蒽酮（3-NBA），柴油机废气的一个组成部分的实验，并考虑到以下代谢途径的抗氧化防御系统：谷胱甘肽氧化还原循环直接清除活性氧，戊糖磷酸途径和葡萄糖酸分流NADPH供应商和糖酵解的开始。此外，由于3-NBA的生物活化而产生的ROS已经被实施。酶活性的调节在所提出的数学模型中起着重要的作用。该电子模型由基于酶动力学和质量作用的3-NBA代谢的常微分方程组成。参数估计performedin vitroexperiments通过最小二乘拟合或从文献中获得。结果强调了戊糖磷酸途径科普氧化应激的重要性，并表明葡萄糖酸盐分流在低剂量暴露期间的重要作用。
Elevated intracellular levels of reactive oxygen species (ROS), e.g. resulting from exposure to xenobiotics, can cause severe damages. Antioxidant defence mechanisms, which involve regulation of enzyme activities, protect cells to a certain extent. Nevertheless, continuous or increased exposure can overwhelm this system resulting in an adverse cellular state. To simulate exposure scenarios and to investigate the transition to an adverse cellular state, a mathematical model for the dynamics of ROS in response to xenobiotic-induced oxidative stress has been developed. It is based on exposure experiments of human urothelial cells (RT4) to the nitrated polycyclic aromatic hydrocarbon 3-nitrobenzanthrone (3-NBA), a component of diesel engine exhaust, and takes into account the following metabolic pathways of the antioxidant defence system: glutathione redox cycle scavenging directly ROS, the pentose phosphate pathway and the gluconate shunt as NADPH supplier and the beginning of glycolysis. In addition, ROS generation due to the bioactivation of 3-NBA has been implemented. The regulation of enzyme activities plays an important role in the presented mathematical model. Thein silicomodel consists of ordinary differential equations on the basis of enzyme kinetics and mass action for the metabolism of 3-NBA. Parameters are either estimated from performedin vitroexperiments via least-squares fitting or obtained from the literature. The results underline the importance of the pentose phosphate pathway to cope with oxidative stress and suggest an important role of the gluconate shunt during low-dose exposure.
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DOI：
--
发表时间：
1992
期刊：
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DOI：
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发表时间：
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期刊：
Comparative Biochemistry and Physiology Part B Comparative Biochemistry
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影响因子：
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