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Antioxidants
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NO Role in Evolution: Significance and Signaling
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NO Role in Evolution: Significance and Signaling

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "ROS, RNS and RSS".

Deadline for manuscript submissions: closed (20 August 2022) | Viewed by 21733

Special Issue Editors

Dr. Paola Corti

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Guest Editor
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
Interests: zebrafish; cardiovascular development; heart regeneration; globins, nitrite; nitrate; NO signaling; Cytoglobin; Globin X; Myoglobin; cell biology; vascular biology; redox signaling; CRISPr/Cas9; mutagenesis
Dr. Daniela Giordano

E-Mail Website
Guest Editor
Institute of Biosciences and BioResources (IBBR), Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, I-80131 Naples, Italy
Interests: antarctic and arctic marine environments; bacteria; fish; sponges; marine natural products; marine peptides/proteins; protein structure/function; hemoproteins; marine antioxidants; marine anti-UV; functional ingredients; cosmeceuticals; PUFA
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Bulent Mutus

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Guest Editor
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada
Interests: enzymology; protein structure-function; redox signalling; dynamic microscopy; cell biology; intravital fluorescent probes; nanosensors for nitric oxide; thiols and NOx; platelet biochemistry; flow devices; environmental sensor development; the use of biopolymers for the mitigation of environmental phosphate
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nitric Oxide (NO) is a signaling molecule that mediates diverse pathways in target cells playing an important role in many physiological processes. The importance of NO in cells is traceable back to the origin of life as a known bioproduct in almost all types of organisms, ranging from bacteria and fungi to plants and animal cells. Its function ranges from antimicrobial, tumoricidal and cytoprotective to tissue-damaging effect molecule, apoptotic and proliferative. The extent and variety of NO effects greatly depends on the system involved, due to the pleiotropic and versatile signaling functions of NO. Whether the NO sources are environmentally available in the form of nitrite, nitrate, nitroso species or whether NO is generated by specially evolved enzymes, as a ubiquitous molecular mediator in biology NO has shaped the evolution of organisms. 

Because the pathway of NO formation and signaling may be one of the oldest bioregulatory systems controlling human and animal physiology, the question arises why such molecule should serve so many purposes in regulating diverse and complex cellular functions. What’s the function of NO in the evolution of organisms? From a wider perspective, the study of the molecular basis of NO signaling in different systems can uncover the role of NO in human metabolism under normal conditions and in the context of environmental changes that can lead to cellular dysfunction and human disease. 

As Guest Editors of this Special Issue, we invite authors to submit original research articles as well as review articles that will contribute to broadening the understanding of the biochemical, cellular and molecular mechanisms regulated by NO. We are particularly interested in articles covering the significance of the evolved function of NO in biology. 

The potential topics include but are not limited to the following:

  • The early role of NO in evolution.
  • NO as a defense against pathogens.
  • NO as an endogenous messenger in multicellular organisms.
  • The concept of the NO microenvironment in animal physiology.
  • NO’s function in the morphogenesis and development of plants.
  • The multiplicity of NO synthetic pathways in organisms.
  • The diversification and lineage-specific expansion of NO signaling.

Dr. Paola Corti
Dr. Daniela Giordano
Prof. Dr. Bulent Mutus
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 submissions that pass pre-check are 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. Antioxidants 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 2900 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

  • Nitric Oxide
  • Evolution
  • ROS and RNS
  • NO signaling
  • Nitrosative stress
  • SNO
  • Nitrite
  • Nitrate
  • NO synthase
  • Soluble guanylyl cyclase

Published Papers (7 papers)

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Research

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19 pages, 4197 KiB  
Article
Nitric Oxide Sensing by a Blue Fluorescent Protein
by Chiara Montali, Stefania Abbruzzetti, Arne Franzen, Giorgia Casini, Stefano Bruno, Pietro Delcanale, Sandra Burgstaller, Jeta Ramadani-Muja, Roland Malli, Thomas Gensch and Cristiano Viappiani
Antioxidants 2022, 11(11), 2229; https://doi.org/10.3390/antiox11112229 - 11 Nov 2022
Cited by 2 | Viewed by 1621
Abstract
S-Nitrosylation of cysteine residues is an important molecular mechanism for dynamic, post-translational regulation of several proteins, providing a ubiquitous redox regulation. Cys residues are present in several fluorescent proteins (FP), including members of the family of Aequorea victoria Green Fluorescent Protein (GFP)-derived FPs, [...] Read more.
S-Nitrosylation of cysteine residues is an important molecular mechanism for dynamic, post-translational regulation of several proteins, providing a ubiquitous redox regulation. Cys residues are present in several fluorescent proteins (FP), including members of the family of Aequorea victoria Green Fluorescent Protein (GFP)-derived FPs, where two highly conserved cysteine residues contribute to a favorable environment for the autocatalytic chromophore formation reaction. The effect of nitric oxide on the fluorescence properties of FPs has not been investigated thus far, despite the tremendous role FPs have played for 25 years as tools in cell biology. We have examined the response to nitric oxide of fluorescence emission by the blue-emitting fluorescent protein mTagBFP2. To our surprise, upon exposure to micromolar concentrations of nitric oxide, we observed a roughly 30% reduction in fluorescence quantum yield and lifetime. Recovery of fluorescence emission is observed after treatment with Na-dithionite. Experiments on related fluorescent proteins from different families show similar nitric oxide sensitivity of their fluorescence. We correlate the effect with S-nitrosylation of Cys residues. Mutation of Cys residues in mTagBFP2 removes its nitric oxide sensitivity. Similarly, fluorescent proteins devoid of Cys residues are insensitive to nitric oxide. We finally show that mTagBFP2 can sense exogenously generated nitric oxide when expressed in a living mammalian cell. We propose mTagBFP2 as the starting point for a new class of genetically encoded nitric oxide sensors based on fluorescence lifetime imaging. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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13 pages, 2241 KiB  
Article
Arginine-Dependent Nitric Oxide Generation and S-Nitrosation in the Non-Photosynthetic Unicellular Alga Polytomella parva
by Tatiana Lapina, Vladislav Statinov, Roman Puzanskiy and Elena Ermilova
Antioxidants 2022, 11(5), 949; https://doi.org/10.3390/antiox11050949 - 11 May 2022
Cited by 4 | Viewed by 1674
Abstract
Nitric oxide (NO) acts as a key signaling molecule in higher plants, regulating many physiological processes. Several photosynthetic algae from different lineages are also known to produce NO. However, it remains unclear whether this messenger is produced by non-photosynthetic algae. Among these organisms, [...] Read more.
Nitric oxide (NO) acts as a key signaling molecule in higher plants, regulating many physiological processes. Several photosynthetic algae from different lineages are also known to produce NO. However, it remains unclear whether this messenger is produced by non-photosynthetic algae. Among these organisms, the colorless alga Polytomella parva is a special case, as it has lost not only its plastid genome, but also nitrate reductase and nitrite reductase. Up to now, the question of whether NO synthesis occurs in the absence of functional nitrate reductase (NR) and the assimilation of nitrates/nitrites in P. parva has not been elucidated. Using spectrofluorometric assays and confocal microscopy with NO-sensitive fluorescence dye, we demonstrate L-arginine-dependent NO synthesis by P. parva cells. Based on a pharmacological approach, we propose the existence of arginine-dependent NO synthase-like activity in this non-photosynthetic alga. GC-MS analysis provides primary evidence that P. parva synthesizes putrescine, which is not an NO source in this alga. Moreover, the generated NO causes the S-nitrosation of protein cysteine thiol groups. Together, our data argue for NR-independent NO synthesis and its active role in S-nitrosation as an essential post-translational modification in P. parva. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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14 pages, 1658 KiB  
Article
Redox-Regulation of α-Globin in Vascular Physiology
by Laurent Kiger, Julia Keith, Abdullah Freiwan, Alfonso G. Fernandez, Heather Tillman, Brant E. Isakson, Mitchell J. Weiss and Christophe Lechauve
Antioxidants 2022, 11(1), 159; https://doi.org/10.3390/antiox11010159 - 14 Jan 2022
Cited by 4 | Viewed by 2081
Abstract
Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric [...] Read more.
Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that α-globin can be reduced by either of two independent redox systems, CyB5R3/CyB5a and eNOS. Together, our findings provide new insights into the regulation of blood vessel contractility. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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Review

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21 pages, 3431 KiB  
Review
Strategies of Pathogens to Escape from NO-Based Host Defense
by Giovanna De Simone, Alessandra di Masi and Paolo Ascenzi
Antioxidants 2022, 11(11), 2176; https://doi.org/10.3390/antiox11112176 - 3 Nov 2022
Cited by 4 | Viewed by 1679
Abstract
Nitric oxide (NO) is an essential signaling molecule present in most living organisms including bacteria, fungi, plants, and animals. NO participates in a wide range of biological processes including vasomotor tone, neurotransmission, and immune response. However, NO is highly reactive and can give [...] Read more.
Nitric oxide (NO) is an essential signaling molecule present in most living organisms including bacteria, fungi, plants, and animals. NO participates in a wide range of biological processes including vasomotor tone, neurotransmission, and immune response. However, NO is highly reactive and can give rise to reactive nitrogen and oxygen species that, in turn, can modify a broad range of biomolecules. Much evidence supports the critical role of NO in the virulence and replication of viruses, bacteria, protozoan, metazoan, and fungi, thus representing a general mechanism of host defense. However, pathogens have developed different mechanisms to elude the host NO and to protect themselves against oxidative and nitrosative stress. Here, the strategies evolved by viruses, bacteria, protozoan, metazoan, and fungi to escape from the NO-based host defense are overviewed. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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35 pages, 3017 KiB  
Review
The Breast Cancer Protooncogenes HER2, BRCA1 and BRCA2 and Their Regulation by the iNOS/NOS2 Axis
by Katie Lin, Stavroula Baritaki, Silvia Vivarelli, Luca Falzone, Aurora Scalisi, Massimo Libra and Benjamin Bonavida
Antioxidants 2022, 11(6), 1195; https://doi.org/10.3390/antiox11061195 - 17 Jun 2022
Cited by 10 | Viewed by 4132
Abstract
The expression of inducible nitric oxide synthase (iNOS; NOS2) and derived NO in various cancers was reported to exert pro- and anti-tumorigenic effects depending on the levels of expression and the tumor types. In humans, the breast cancer level of iNOS was reported [...] Read more.
The expression of inducible nitric oxide synthase (iNOS; NOS2) and derived NO in various cancers was reported to exert pro- and anti-tumorigenic effects depending on the levels of expression and the tumor types. In humans, the breast cancer level of iNOS was reported to be overexpressed, to exhibit pro-tumorigenic activities, and to be of prognostic significance. Likewise, the expression of the oncogenes HER2, BRCA1, and BRCA2 has been associated with malignancy. The interrelationship between the expression of these protooncogenes and oncogenes and the expression of iNOS is not clear. We have hypothesized that there exist cross-talk signaling pathways between the breast cancer protooncogenes, the iNOS axis, and iNOS-mediated NO mutations of these protooncogenes into oncogenes. We review the molecular regulation of the expression of the protooncogenes in breast cancer and their interrelationships with iNOS expression and activities. In addition, we discuss the roles of iNOS, HER2, BRCA1/2, and NO metabolism in the pathophysiology of cancer stem cells. Bioinformatic analyses have been performed and have found suggested molecular alterations responsible for breast cancer aggressiveness. These include the association of BRCA1/2 mutations and HER2 amplifications with the dysregulation of the NOS pathway. We propose that future studies should be undertaken to investigate the regulatory mechanisms underlying the expression of iNOS and various breast cancer oncogenes, with the aim of identifying new therapeutic targets for the treatment of breast cancers that are refractory to current treatments. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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22 pages, 3241 KiB  
Review
Nitric Oxide Production and Regulation in the Teleost Cardiovascular System
by Daniela Giordano, Cinzia Verde and Paola Corti
Antioxidants 2022, 11(5), 957; https://doi.org/10.3390/antiox11050957 - 12 May 2022
Cited by 6 | Viewed by 3273
Abstract
Nitric Oxide (NO) is a free radical with numerous critical signaling roles in vertebrate physiology. Similar to mammals, in the teleost system the generation of sufficient amounts of NO is critical for the physiological function of the cardiovascular system. At the same time, [...] Read more.
Nitric Oxide (NO) is a free radical with numerous critical signaling roles in vertebrate physiology. Similar to mammals, in the teleost system the generation of sufficient amounts of NO is critical for the physiological function of the cardiovascular system. At the same time, NO amounts are strictly controlled and kept within basal levels to protect cells from NO toxicity. Changes in oxygen tension highly influence NO bioavailability and can modulate the mechanisms involved in maintaining the NO balance. While NO production and signaling appears to have general similarities with mammalian systems, the wide range of environmental adaptations made by fish, particularly with regards to differing oxygen availabilities in aquatic habitats, creates a foundation for a variety of in vivo models characterized by different implications of NO production and signaling. In this review, we present the biology of NO in the teleost cardiovascular system and summarize the mechanisms of NO production and signaling with a special emphasis on the role of globin proteins in NO metabolism. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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20 pages, 2346 KiB  
Review
The Role of Nitric Oxide in Stem Cell Biology
by Estefanía Caballano-Infantes, Gladys Margot Cahuana, Francisco Javier Bedoya, Carmen Salguero-Aranda and Juan R. Tejedo
Antioxidants 2022, 11(3), 497; https://doi.org/10.3390/antiox11030497 - 3 Mar 2022
Cited by 9 | Viewed by 5971
Abstract
Nitric oxide (NO) is a gaseous biomolecule endogenously synthesized with an essential role in embryonic development and several physiological functions, such as regulating mitochondrial respiration and modulation of the immune response. The dual role of NO in embryonic stem cells (ESCs) has been [...] Read more.
Nitric oxide (NO) is a gaseous biomolecule endogenously synthesized with an essential role in embryonic development and several physiological functions, such as regulating mitochondrial respiration and modulation of the immune response. The dual role of NO in embryonic stem cells (ESCs) has been previously reported, preserving pluripotency and cell survival or inducing differentiation with a dose-dependent pattern. In this line, high doses of NO have been used in vitro cultures to induce focused differentiation toward different cell lineages being a key molecule in the regenerative medicine field. Moreover, optimal conditions to promote pluripotency in vitro are essential for their use in advanced therapies. In this sense, the molecular mechanisms underlying stemness regulation by NO have been studied intensively over the current years. Recently, we have reported the role of low NO as a hypoxia-like inducer in pluripotent stem cells (PSCs), which supports using this molecule to maintain pluripotency under normoxic conditions. In this review, we stress the role of NO levels on stem cells (SCs) fate as a new approach for potential cell therapy strategies. Furthermore, we highlight the recent uses of NO in regenerative medicine due to their properties regulating SCs biology. Full article
(This article belongs to the Special Issue NO Role in Evolution: Significance and Signaling)
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