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      Recent advances in hydrogen peroxide imaging for biological applications

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          Abstract

          Mounting evidence supports the role of hydrogen peroxide (H 2O 2) in physiological signaling as well as pathological conditions. However, the subtleties of peroxide-mediated signaling are not well understood, in part because the generation, degradation, and diffusion of H 2O 2 are highly volatile within different cellular compartments. Therefore, the direct measurement of H 2O 2 in living specimens is critically important. Fluorescent probes that can detect small changes in H 2O 2 levels within relevant cellular compartments are important tools to study the spatial dynamics of H 2O 2. To achieve temporal resolution, the probes must also be photostable enough to allow multiple readings over time without loss of signal. Traditional fluorescent redox sensitive probes that have been commonly used for the detection of H 2O 2 tend to react with a wide variety of reactive oxygen species (ROS) and often suffer from photostablilty issues. Recently, new classes of H 2O 2 probes have been designed to detect H 2O 2 with high selectivity. Advances in H 2O 2 measurement have enabled biomedical scientists to study H 2O 2 biology at a level of precision previously unachievable. In addition, new imaging techniques such as two-photon microscopy (TPM) have been employed for H 2O 2 detection, which permit real-time measurements of H 2O 2 in vivo. This review focuses on recent advances in H 2O 2 probe development and optical imaging technologies that have been developed for biomedical applications.

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          Most cited references104

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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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            Fe3O4 magnetic nanoparticles as peroxidase mimetics and their applications in H2O2 and glucose detection.

            Artificial enzyme mimetics are a current research interest because natural enzymes bear some serious disadvantages, such as their catalytic activity can be easily inhibited and they can be digested by proteases. A very recently study reported by Yan et al. has proven that Fe(3)O(4) magnetic nanoparticles (MNPs) exhibit an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, though MNPs are usually thought to be biological and chemical inert (Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Feng, J.; Yang, D. L.; Perrett, S.; Yan, X. Y. Nat. Nanotechnol. 2007, 2, 577-583). In the present work, we just make use of the novel properties of Fe(3)O(4) MNPs as peroxidase mimetics reported by Yan et al. to detect H(2)O(2). The Fe(3)O(4) MNPs were prepared via a coprecipitation method. The as-prepared Fe(3)O(4) MNPs were then used to catalyze the oxidation of a peroxidase substrate 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) by H(2)O(2) to the oxidized colored product (see eq 1) which provides a colorimetric detection of H(2)O(2). As low as 3 x 10(-6) mol/L H(2)O(2) could be detected with a linear range from 5 x 10(-6) to 1 x 10(-4) mol/L via our method. More importantly, a sensitive and selective method for glucose detection was developed using glucose oxidase (GOx) and the as-prepared Fe(3)O(4) MNPs. The detection platforms for H(2)O(2) and glucose developed in the present work not only further confirmed that the Fe(3)O(4) MNPs possess intrinsic peroxidase-like activity but also showed great potential applications in varieties of simple, robust, and easy-to-make analytical approaches in the future.
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              Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling.

              Hydrogen peroxide (H(2)O(2)) produced by cell-surface NADPH Oxidase (Nox) enzymes is emerging as an important signaling molecule for growth, differentiation, and migration processes. However, how cells spatially regulate H(2)O(2) to achieve physiological redox signaling over nonspecific oxidative stress pathways is insufficiently understood. Here we report that the water channel Aquaporin-3 (AQP3) can facilitate the uptake of H(2)O(2) into mammalian cells and mediate downstream intracellular signaling. Molecular imaging with Peroxy Yellow 1 Methyl-Ester (PY1-ME), a new chemoselective fluorescent indicator for H(2)O(2), directly demonstrates that aquaporin isoforms AQP3 and AQP8, but not AQP1, can promote uptake of H(2)O(2) specifically through membranes in mammalian cells. Moreover, we show that intracellular H(2)O(2) accumulation can be modulated up or down based on endogenous AQP3 expression, which in turn can influence downstream cell signaling cascades. Finally, we establish that AQP3 is required for Nox-derived H(2)O(2) signaling upon growth factor stimulation. Taken together, our findings demonstrate that the downstream intracellular effects of H(2)O(2) can be regulated across biological barriers, a discovery that has broad implications for the controlled use of this potentially toxic small molecule for beneficial physiological functions.
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                Author and article information

                Contributors
                hcguo2012@gmail.com
                haleyasin@gmail.com
                Dickinson@uchicago.edu
                haskewlayton@yahoo.com
                rrr2001@med.cornell.edu
                Journal
                Cell Biosci
                Cell Biosci
                Cell & Bioscience
                BioMed Central (London )
                2045-3701
                27 October 2014
                27 October 2014
                2014
                : 4
                : 1
                : 64
                Affiliations
                [ ]Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742 USA
                [ ]Burke Medical Research Institute, Weill Medical College of Cornell University, White Plains, NY 10605 USA
                [ ]Fishberg Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029 USA
                [ ]Department of Chemistry, The University of Chicago, Chicago, IL 60637 USA
                [ ]School of Health and Natural Sciences, Mercy College, Dobbs Ferry, NY 10522 USA
                Article
                191
                10.1186/2045-3701-4-64
                4232666
                25400906
                580ede5b-f5cc-4331-8529-f7affd8fe07b
                © Guo et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 July 2014
                : 6 October 2014
                Categories
                Review
                Custom metadata
                © The Author(s) 2014

                Cell biology
                hydrogen peroxide (h2o2),reactive oxygen species (ros),molecular imaging,fluorescent probe,nanoparticles,two-photon microscopy,ratiometric imaging,fluorescence lifetime imaging microscopy (flim),chemiluminescence

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