ArticleFree radical biology & medicine2016
Increasing extracellular H2O2 produces a bi-phasic response in intracellular H2O2, with peroxiredoxin hyperoxidation only triggered once the cellular H2O2-buffering capacity is overwhelmed.
Article in Free radical biology & medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 46 citations in OpenAlex.
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- Antioxidant and anti-inflammatory function of Eupatorium adenophora Spreng leaves (EASL) on human intestinal Caco-2 cells treated with tert-butyl hydroperoxide.Scientific reports · 2024Article
- Modelling the Decamerisation Cycle of PRDX1 and the Inhibition-like Effect on Its Peroxidase Activity.Antioxidants (Basel, Switzerland) · 2023Article
- Methionine Sources Differently Affect Production of Reactive Oxygen Species, Mitochondrial Bioenergetics, and Growth of Murine and Quail Myoblasts In Vitro.Current issues in molecular biology · 2023Article
- NDP52 acts as a redox sensor in PINK1/Parkin-mediated mitophagy.The EMBO journal · 2023Article
- Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022Review
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- Can thiol-based redox systems be utilized as parts for synthetic biology applications?Redox report : communications in free radical research · 2021Article
- Oxidative Stress Enhances Autophagy-Mediated Death Of Stem Cells Through Erk1/2 Signaling Pathway - Implications For Neurotransplantations.Stem cell reviews and reports · 2021Article
- On the mechanisms underlying attenuated redox responses to exercise in older individuals: A hypothesis.Free radical biology & medicine · 2020Article
- PiQSARS: A pipeline for quantitative and statistical analyses of ratiometric fluorescent biosensors.MethodsX · 2020Article
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- Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.Antioxidants & redox signaling · 2018Review
- HIV-1 tat expression and sulphamethoxazole hydroxylamine mediated oxidative stress alter the disulfide proteome in Jurkat T cells.Virology journal · 2018Article
- Mapping the phenotypic repertoire of the cytoplasmic 2-Cys peroxiredoxin - Thioredoxin system. 1. Understanding commonalities and differences among cell types.Redox biology · 2018Article
- A Two-Photon Ratiometric Fluorescent Probe for Imaging of Hydrogen Peroxide Levels in Rat Organ Tissues.ChemistryOpen · 2018Article
- Localized redox relays as a privileged mode of cytoplasmic hydrogen peroxide signaling.Redox biology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.