4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Hydrogen peroxide reactivity and specificity in thiol-based cell signalling

      1
      Biochemical Society Transactions
      Portland Press Ltd.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Reversible oxidation of thiol proteins is an important cell signalling mechanism. In many cases, this involves generation or exposure of the cells to H2O2, and oxidation of proteins that are not particularly H2O2-reactive. There is a conundrum as to how these proteins are oxidised when other highly reactive proteins such as peroxiredoxins are present. This article discusses potential mechanisms, focussing on recent evidence for oxidation being localised within the cell, redox relays involving peroxiredoxins operating in some signalling pathways, and mechanisms for facilitated or directed oxidation of specific targets. These findings help define conditions that enable redox signalling but there is still much to learn regarding mechanisms.

          Related collections

          Most cited references78

          • Record: found
          • Abstract: found
          • Article: not found

          ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis.

          Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. This biological paradox underlies mechanisms that are important for the integrity and fitness of living organisms and their ageing. The pathways that regulate ROS homeostasis are crucial for mitigating the toxicity of ROS and provide strong evidence about specificity in ROS signalling. By taking advantage of the chemistry of ROS, highly specific mechanisms have evolved that form the basis of oxidant scavenging and ROS signalling systems.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.

            Apoptosis signal-regulating kinase (ASK) 1 was recently identified as a mitogen-activated protein (MAP) kinase kinase kinase which activates the c-Jun N-terminal kinase (JNK) and p38 MAP kinase pathways and is required for tumor necrosis factor (TNF)-alpha-induced apoptosis; however, the mechanism regulating ASK1 activity is unknown. Through genetic screening for ASK1-binding proteins, thioredoxin (Trx), a reduction/oxidation (redox)-regulatory protein thought to have anti-apoptotic effects, was identified as an interacting partner of ASK1. Trx associated with the N-terminal portion of ASK1 in vitro and in vivo. Expression of Trx inhibited ASK1 kinase activity and the subsequent ASK1-dependent apoptosis. Treatment of cells with N-acetyl-L-cysteine also inhibited serum withdrawal-, TNF-alpha- and hydrogen peroxide-induced activation of ASK1 as well as apoptosis. The interaction between Trx and ASK1 was found to be highly dependent on the redox status of Trx. Moreover, inhibition of Trx resulted in activation of endogenous ASK1 activity, suggesting that Trx is a physiological inhibitor of ASK1. The evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine- and stress-induced apoptosis.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Signal transduction by reactive oxygen species

              Although historically viewed as purely harmful, recent evidence suggests that reactive oxygen species (ROS) function as important physiological regulators of intracellular signaling pathways. The specific effects of ROS are modulated in large part through the covalent modification of specific cysteine residues found within redox-sensitive target proteins. Oxidation of these specific and reactive cysteine residues in turn can lead to the reversible modification of enzymatic activity. Emerging evidence suggests that ROS regulate diverse physiological parameters ranging from the response to growth factor stimulation to the generation of the inflammatory response, and that dysregulated ROS signaling may contribute to a host of human diseases.
                Bookmark

                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Biochemical Society Transactions
                Portland Press Ltd.
                0300-5127
                1470-8752
                June 30 2020
                May 15 2020
                June 30 2020
                May 15 2020
                : 48
                : 3
                : 745-754
                Affiliations
                [1 ]Centre for Free Radical Research, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand
                Article
                10.1042/BST20190049
                32412042
                75b7d68d-5a60-4294-be3b-eaef86250ca9
                © 2020
                History

                Comments

                Comment on this article