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Using in vivo oxidation status of one- and two-component redox relays to determine H2O2 levels linked to signaling and toxicity.
Domènech, Alba; Ayté, José; Antunes, Fernando; Hidalgo, Elena.
Afiliação
  • Domènech A; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003, Barcelona, Spain.
  • Ayté J; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003, Barcelona, Spain.
  • Antunes F; Departamento de Química e Bioquímica and Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisbon, Portugal. fantunes@fc.ul.pt.
  • Hidalgo E; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, C/ Dr. Aiguader 88, 08003, Barcelona, Spain. elena.hidalgo@upf.edu.
BMC Biol ; 16(1): 61, 2018 06 01.
Article em En | MEDLINE | ID: mdl-29859088
BACKGROUND: Hydrogen peroxide (H2O2) is generated as a by-product of metabolic reactions during oxygen use by aerobic organisms, and can be toxic or participate in signaling processes. Cells, therefore, need to be able to sense and respond to H2O2 in an appropriate manner. This is often accomplished through thiol switches: Cysteine residues in proteins that can act as sensors, and which are both scarce and finely tuned. Bacteria and eukaryotes use different types of such sensors-either a one-component (OxyR) or two-component (Pap1-Tpx1) redox relay, respectively. However, the biological significance of these two different signaling modes is not fully understood, and the concentrations and peroxides driving those types of redox cascades have not been determined, nor the intracellular H2O2 levels linked to toxicity. Here we elucidate the characteristics, rates, and dynamic ranges of both systems. RESULTS: By comparing the activation of both systems in fission yeast, and applying mathematical equations to the experimental data, we estimate the toxic threshold of intracellular H2O2 able to halt aerobic growth, and the temporal gradients of extracellular to intracellular peroxides. By calculating both the oxidation rates of OxyR and Tpx1 by peroxides, and their reduction rates by the cellular redoxin systems, we propose that, while Tpx1 is a sensor and an efficient H2O2 scavenger because it displays fast oxidation and reduction rates, OxyR is strictly a H2O2 sensor, since its reduction kinetics are significantly slower than its oxidation by peroxides, and therefore, it remains oxidized long enough to execute its transcriptional role. We also show that these two paradigmatic H2O2-sensing models are biologically similar at pre-toxic peroxide levels, but display strikingly different activation behaviors at toxic doses. CONCLUSIONS: Both Tpx1 and OxyR contain thiol switches, with very high reactivity towards peroxides. Nevertheless, the fast reduction of Tpx1 defines it as a scavenger, and this efficient recycling dramatically changes the Tpx1-Pap1 response to H2O2 and connects H2O2 sensing to the redox state of the cell. In contrast, OxyR is a true H2O2 sensor but not a scavenger, being partially insulated from the cellular electron donor capacity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Schizosaccharomyces / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Schizosaccharomyces / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2018 Tipo de documento: Article