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      The Role of Hydrogen Peroxide in Redox-Dependent Signaling: Homeostatic and Pathological Responses in Mammalian Cells

      review-article
      , , *
      Cells
      MDPI
      hydrogen peroxide, redox regulation, oxidative stress

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          Abstract

          Hydrogen peroxide (H 2O 2) is an important metabolite involved in most of the redox metabolism reactions and processes of the cells. H 2O 2 is recognized as one of the main molecules in the sensing, modulation and signaling of redox metabolism, and it is acting as a second messenger together with hydrogen sulfide (H 2S) and nitric oxide (NO). These second messengers activate in turn a cascade of downstream proteins via specific oxidations leading to a metabolic response of the cell. This metabolic response can determine proliferation, survival or death of the cell depending on which downstream pathways (homeostatic, pathological, or protective) have been activated. The cells have several sources of H 2O 2 and cellular systems strictly control its concentration in different subcellular compartments. This review summarizes research on the role played by H 2O 2 in signaling pathways of eukaryotic cells and how this signaling leads to homeostatic or pathological responses.

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          Most cited references83

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          Is Open Access

          Lipid peroxidation in cell death.

          Disruption of redox homeostasis is a key phenotype of many pathological conditions. Though multiple oxidizing compounds such as hydrogen peroxide are widely recognized as mediators and inducers of oxidative stress, increasingly, attention is focused on the role of lipid hydroperoxides as critical mediators of death and disease. As the main component of cellular membranes, lipids have an indispensible role in maintaining the structural integrity of cells. Excessive oxidation of lipids alters the physical properties of cellular membranes and can cause covalent modification of proteins and nucleic acids. This review discusses the synthesis, toxicity, degradation, and detection of lipid peroxides in biological systems. Additionally, the role of lipid peroxidation is highlighted in cell death and disease, and strategies to control the accumulation of lipid peroxides are discussed.
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            Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling

            Wang et al. review the dual role of superoxide dismutases in controlling reactive oxygen species (ROS) damage and regulating ROS signaling across model systems as well as their involvement in human diseases.
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              A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish

              Barrier structures (e.g. epithelia around tissues, plasma membranes around cells) are required for internal homeostasis and protection from pathogens. Wound detection and healing represent a dormant morphogenetic program that can be rapidly executed to restore barrier integrity and tissue homeostasis. In animals, initial steps include recruitment of leukocytes to the site of injury across distances of hundreds of micrometers within minutes of wounding. The spatial signals that direct this immediate tissue response are unknown. Due to their fast diffusion and versatile biological activities, reactive oxygen species (ROS), including hydrogen peroxide (H2O2), are interesting candidates for wound-to-leukocyte signalling. We probed the role of H2O2 during the early events of wound responses in zebrafish larvae expressing a genetically encoded H2O2 sensor1. This reporter revealed a sustained rise in H2O2 concentration at the wound margin, starting ∼3 min after wounding and peaking at ∼20 min, which extended ∼100−200 μm into the tail fin epithelium as a decreasing concentration gradient. Using pharmacological and genetic inhibition, we show that this gradient is created by Dual oxidase (Duox), and that it is required for rapid recruitment of leukocytes to the wound. This is the first observation of a tissue-scale H2O2 pattern, and the first evidence that H2O2 signals to leukocytes in tissues, in addition to its known antiseptic role.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                04 October 2018
                October 2018
                : 7
                : 10
                : 156
                Affiliations
                School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza, Italy; noemi.dimarzo91@ 123456gmail.com (N.D.M.); e.chisci4@ 123456gmail.com (E.C.)
                Author notes
                [* ]Correspondence: roberto.giovannoni@ 123456unimib.it ; Tel.: +39-333-4995473
                [†]

                Current address: Department of Biology, University of Pisa, roberto.giovannoni@ 123456unipi.it .

                Author information
                https://orcid.org/0000-0002-7706-0672
                Article
                cells-07-00156
                10.3390/cells7100156
                6211135
                30287799
                fba68642-2e30-4444-a3a5-db5be95216f1
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 02 September 2018
                : 03 October 2018
                Categories
                Review

                hydrogen peroxide,redox regulation,oxidative stress
                hydrogen peroxide, redox regulation, oxidative stress

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