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The thioredoxin redox potential and redox charge are surrogate measures for flux in the thioredoxin system.
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2019-12-23 , DOI: 10.1016/j.abb.2019.108231
Letrisha Padayachee 1 , Johann M Rohwer 2 , Ché S Pillay 1
Affiliation  

The thioredoxin system plays a central role in intracellular redox regulation and its dysregulation is associated with a number of pathologies. However, the connectivity within this system poses a significant challenge for quantification and consequently several disparate measures have been used to characterize the system. For in vitro studies, the thioredoxin system flux has been measured by NADPH oxidation while the thioredoxin redox state has been used to estimate the activity of the system in vivo. The connection between these measures has been obscure although substrate saturation in the thioredoxin system results from the saturation of the thioredoxin redox cycle. We used computational modeling and in vitro kinetic assays to clarify the relationship between flux and the current in vivo measures of the thioredoxin system together with a novel measure, the thioredoxin redox charge (reduced thioredoxin/total thioredoxin). Our results revealed that the thioredoxin redox potential and redox charge closely tracked flux perturbations showing that these indices could be used as surrogate measures of the flux in vivo and, provide a mechanistic explanation for the previously observed correlations between thioredoxin oxidation and certain pathologies. While we found no significant difference in the linear correlations obtained for the thioredoxin redox potential and redox charge with the flux, the redox charge may be preferred because it is bounded between zero and one and can be determined over a wider range of conditions allowing for quantitative flux comparisons between cell types and conditions.

中文翻译:

硫氧还蛋白的氧化还原电势和氧化还原电荷是硫氧还蛋白系统中通量的替代量度。

硫氧还蛋白系统在细胞内氧化还原调节中起着核心作用,其调节异常与多种病理相关。然而,该系统内的连通性对量化提出了重大挑战,因此,已经使用了几种不同的方法来表征系统。对于体外研究,已通过NADPH氧化法测定了硫氧还蛋白系统的通量,而硫氧还蛋白的氧化还原状态已用于评估系统在体内的活性。尽管由于硫氧还蛋白氧化还原循环的饱和而导致硫氧还蛋白系统中的底物饱和,但是这些措施之间的联系却不清楚。我们使用计算模型和体外动力学分析来阐明通量与硫氧还蛋白系统的当前体内测量值之间的关系,以及一种新的方法,硫氧还蛋白氧化还原电荷(还原的硫氧还蛋白/总硫氧还蛋白)。我们的结果表明,硫氧还蛋白的氧化还原电势和氧化还原电荷密切跟踪通量扰动,表明这些指数可用作体内通量的替代指标,并为先前观察到的硫氧还蛋白氧化与某些病理之间的相关性提供了机械解释。虽然我们发现,硫氧还蛋白氧化还原电势和氧化还原电荷与通量之间的线性相关性没有显着差异,
更新日期:2019-12-23
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