دورية أكاديمية
Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed
| العنوان: | Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed |
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| المؤلفون: | Tomalin, LE, Day, AM, Underwood, ZE, Smith, GR, Pezze, PD, Rallis, C, Patel, W, Dickinson, BC, Bähler, J, Brewer, TF, Chang, CJ, Shanley, DP, Veal, EA |
| المصدر: | Free Radical Biology and Medicine , 95 pp. 333-348. (2016) |
| سنة النشر: | 2016 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Computational model, Hydrogen peroxide, Oxidation, Peroxiredoxin, Signaling, Thiol, Thioredoxin |
| الوصف: | Reactive oxygen species, such as H2O2, can damage cells but also promote fundamental processes, including growth, differentiation and migration. The mechanisms allowing cells to differentially respond to toxic or signaling H2O2 levels are poorly defined. Here we reveal that increasing external H2O2 produces a bi-phasic response in intracellular H2O2. Peroxiredoxins (Prx) are abundant peroxidases which protect against genome instability, ageing and cancer. We have developed a dynamic model simulating in vivo changes in Prx oxidation. Remarkably, we show that the thioredoxin peroxidase activity of Prx does not provide any significant protection against external rises in H2O2. Instead, our model and experimental data are consistent with low levels of extracellular H2O2 being efficiently buffered by other thioredoxin-dependent activities, including H2O2-reactive cysteines in the thiol-proteome. We show that when extracellular H2O2 levels overwhelm this buffering capacity, the consequent rise in intracellular H2O2 triggers hyperoxidation of Prx to thioredoxin-resistant, peroxidase-inactive form/s. Accordingly, Prx hyperoxidation signals that H2O2 defenses are breached, diverting thioredoxin to repair damage. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/1476449/1/1-s2.0-S0891584916000940-main.pdfTest; https://discovery.ucl.ac.uk/id/eprint/1476449Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/1476449/1/1-s2.0-S0891584916000940-main.pdfTest https://discovery.ucl.ac.uk/id/eprint/1476449Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.1A47C1C8 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |