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Special Issue "Biology of Reactive Oxygen and Nitrogen Species: Redox Signaling, Metabolic Effects, Cellular Functions and Oxidative Damage"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: 31 July 2018

Special Issue Editors

Guest Editor
Assoc. Prof. Dr. Andrey V. Kozlov

Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria
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Interests: mitochondria; reactive oxygen and nitrogen species; endoplasmic reticulum (-stress); iron metabolism; organ failure; inflammation; hypoxia; critical care diseases
Guest Editor
Assoc. Prof. Dr. Sergey Dikalov

Vanderbilt University, Clinical Pharmacology Department, 2200 Pierce Ave, 558 PRB, Nashville, TN 37232, USA
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Special Issue Information

Dear Colleagues,

For a long time, reactive oxygen and nitrogen species (RONS) were considered as deleterious chemically-active molecules causing oxidative damage to nearly all types of biomolecules. More recently, RONS have been discovered as regulators of diverse intracellular processes, such as redox signalling, metabolic processes, and cellular functions. Thus, the biological impact of RONS is a sum of diverse and possibly even opposite effects, which can modulate physiological processes and also contribute to the development of a disease.

Consideration of possible mechanism switching between beneficial and deleterious effects of RONS led to a rather common assumption, that low levels of ROS activate signalling pathways while oxidative stress denotes high levels of ROS. However, numerous reports on the chemistry of RONS show, that molecules jointly named RONS indeed have quite different chemical properties and consequently must have different biological effects. Some of these species are more suitable for physiological reactions, while the others exert predominantly damaging capacity. Thus, the identification of specific RONS occurring in biological systems is as important as the determination of total amount of RONS formed.

This Special Issue will focus on two aspects of RONS biology indicated above. The first one, which considers the links between RONS and diverse cellular/organ functions as well as impact of RONS on clinical outcomes. The second aspect is related to the identification of specific type of RONS involved in the regulation of diverse cellular/organ functions, particular those relevant for development of diseases. Papers addressing both aspects simultaneously will be greatly favored.

Assoc. Prof. Dr. Andrey V. Kozlov
Assoc. Prof. Dr. Sergey Dikalov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • superoxide radical
  • hydrogen peroxide
  • peroxynitrite
  • mitochondria
  • peroxisome
  • NADPH-oxidase
  • hypoxia
  • inflammation
  • redox signaling
  • gene expression
  • metabolism
  • cellular functions

Published Papers (2 papers)

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Research

Open AccessArticle Computational Modeling of In Vitro Swelling of Mitochondria: A Biophysical Approach
Molecules 2018, 23(4), 783; doi:10.3390/molecules23040783
Received: 22 February 2018 / Revised: 12 March 2018 / Accepted: 27 March 2018 / Published: 28 March 2018
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Abstract
Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the
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Swelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier. Full article
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Open AccessArticle Miro1 Enhances Mitochondria Transfer from Multipotent Mesenchymal Stem Cells (MMSC) to Neural Cells and Improves the Efficacy of Cell Recovery
Molecules 2018, 23(3), 687; doi:10.3390/molecules23030687
Received: 22 February 2018 / Revised: 13 March 2018 / Accepted: 17 March 2018 / Published: 19 March 2018
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Abstract
A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models
[...] Read more.
A recently discovered key role of reactive oxygen species (ROS) in mitochondrial traffic has opened a wide alley for studying the interactions between cells, including stem cells. Since its discovery in 2006, intercellular mitochondria transport has been intensively studied in different cellular models as a basis for cell therapy, since the potential of replacing malfunctioning organelles appears to be very promising. In this study, we explored the transfer of mitochondria from multipotent mesenchymal stem cells (MMSC) to neural cells and analyzed its efficacy under normal conditions and upon induction of mitochondrial damage. We found that mitochondria were transferred from the MMSC to astrocytes in a more efficient manner when the astrocytes were exposed to ischemic damage associated with elevated ROS levels. Such transport of mitochondria restored the bioenergetics of the recipient cells and stimulated their proliferation. The introduction of MMSC with overexpressed Miro1 in animals that had undergone an experimental stroke led to significantly improved recovery of neurological functions. Our data suggest that mitochondrial impairment in differentiated cells can be compensated by receiving healthy mitochondria from MMSC. We demonstrate a key role of Miro1, which promotes the mitochondrial transfer from MMSC and suggest that the genetic modification of stem cells can improve the therapies for the injured brain. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Dual Effect of Complex Nutritional Supplement on Inflammatory Response and Oxidative Stress in Humans
Author:
Bruno Fink
Affiliation: Noxygen Science Transfer & Diagnostics GmbH Lindenmatte 4279215 Elzach, Germany
Email: bruno.fink@noxygen.de

Title: Sodium Nitrite Mediates Human Hepatocyte Cytoprotection
Authors: John D. Lang * and Sufang Yang
Affiliation: Department of Anesthesiology & Pain Medicine, University of Washington, Seattle, WA, USA
Email: jdlang@uw.edu
Abstract: Background: Systemic inflammatory responses (SIRS) lead to a myriad of undesirable events including microvascular failure resulting in tissue hypoxia; mitochondrial damage and dysfunction causing “metabolic” hypoxia; and reactive nitrogen and oxygen species exerting direct cytotoxic effects. Fundamental to SIRS and sepsis is that nitric oxide (NO) production has been suggested to cause harmful effects including circulatory failure, inflammatory injury, cell cytotoxicity and inhibition of mitochondrial enzyme complexes. Inconsistent with these beliefs is that NO or carriers of NO such as nitrite, may actually reduce injury, enhance oxygen delivery and utilization, and improve outcomes. In models of ischemia-reperfusion injury not sepsis, treatment with nitrite decreased injury via reductions in mitochondrial complex I (through S-nitrosylation) and IV activity. This lessened reactive oxygen species production thus diminished injury during re-oxygenation. Treatment with nitrite has also been associated with decreased release of cytochrome c and suppression of cellular apoptosis. We hypothesized that nitrite, a molecule reduced to NO, would decrease cytotoxic injury in LPS-injured hepatocytes.
Methods: Experimental protocols were approved by the University of Washington Institutional Human Care and Use Committee and conform to NIH guidelines. Primary human hepatocytes were exposed 10μg/ml LPS for 8 hrs and experiments conducted for an additional 24 hrs unless otherwise specified. For measurement of ATP production, cytochrome c, caspase-3 and nitrotyrosine, cells were pre-incubated with 2.5μM SN for 2 hrs, followed by exposure to 10μg/ml LPS 24 hrs. iNOS expression was measured at 6 hrs (versus 24) via Western Blot analysis under the exact conditions. For detection of S-nitrosylated proteins, a biotin switch method was employed at 24 hrs.
Results: Compared to controls hepatocytes treated with LPS had significantly decreased ATP production, increased cytochrome c release, increased caspase-3 release, increased iNOS expression, increased nitrotyrosine formation, and decreased protein S-nitrosylation. Pretreatment with 2.5 μM nitrite resulted in significant restoration of ATP production, reduced cytochrome c release, decreased caspase-c release, decreased iNOS expression, increased nitrotyrosine formation (not significant), and increased protein S-nitrosylation.
Discussion: SIRS and sepsis are characterized by excessive NO production resulting in undesirable effects and outcomes. Global inhibition of NO has also been associated with the same unfavorable effects thus demonstrates some requirement of NO for optimal vital organ performance. In our crude model of SIRS/sepsis, we demonstrated that hepatocyte cytoprotection is afforded with nitrite. The exact mechanism for this observation is not known, but appears to be multimodal and includes reductions in iNOS expression and modulation of critical mitochondrial processes. Future investigations should include large animal investigations that focus on nitrite’s effects on vital organ function and overall survival.

Title: Nitric Oxide: Signal Messenger and Cytotoxic Agent
Authors:
E.M. Sokolova and N.I. Neshev *
Affiliation: Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 Academician Semenov Avenue, Chernogolovka, Moscow region, 142432.
Email: neshev@icp.ac.ru
Abstract: Nitric oxide (II) or nitric monoxide is one of the five oxygen compounds of nitrogen which was known in the chemistry for a long time. However for the past decades this compound has acquired so wide fame in biology and medicine, that in the biological scientific literature it gained the simple denomination - nitric oxide, without any fear of misunderstandings. As it turned out, this simple molecule, which until recently was known to biologists only as a highly toxic environment pollutant, as long ago as at the dawn of evolution was included by nature in the biochemistry and physiology of multicellular organisms. Moreover, evolution secured to this small-sized molecule, not just one, but two important physiological functions: the function of a signal messenger in intercellular communication and the function of a cytotoxic agent in a system of nonspecific immunity. Our goal was to show what specific physical and/or chemical properties of nitric oxide were called forth by nature in the first and second cases, and which biochemical processes link the primary chemical action of NO with the final physiological response. Separately, various views on the role of hemoglobin in the NO-signaling system are discussed. In the final section of the review, the experience and prospects for application of NO-donors as pharmacological regulators of physiological functions are analyzed.

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