Nitric Oxide and Redox Mechanisms

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 April 2025) | Viewed by 4847

Special Issue Editors


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IRCCS Fondazione Bietti, 00198 Roma, Italy
Interests: haptoglobins; haptoglobin–hemoglobin complex; human HP protein ATP-dependent 26S protease; proteasome endopeptidase complex; ubiquitin; cytochrome C; cardiolipins; heme

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1. Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, 00146 Rome, Italy
2. Interdepartmental Laboratory of Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, I-00146 Rome, Italy
Interests: hemoglobin; albumin; biochemistry; molecular biology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, 00146 Rome, Italy
Interests: biochemistry; nitrobindin; cell stress; molecular biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nitric oxide (NO) is an essential signaling molecule present in most living organisms, including bacteria, fungi, plants, and animals. It participates in a wide range of biological processes, including vasomotor tone, neurotransmission, and immune response, and is highly reactive, able to give rise to reactive nitrogen and oxygen species that can modify a broad range of biomolecules.

The interplay between NO and redox mechanisms extends to diverse cellular processes, from regulating gene expression to mediating oxidative stress responses. Furthermore, the dysregulation of NO signaling or redox balance is implicated in numerous pathological conditions, such as cardiovascular diseases, neurodegenerative disorders, and cancer.

We invite authors to submit original research and review articles that will contribute to the understanding of the biochemical, cellular, and molecular mechanisms regulated by NO, attempting to uncover the intricate relationship between NO and redox mechanisms.

The contributions may include in silico, in vitro, and in vivo studies related to the following topics:

  • Heme–protein interactions in NO signaling pathways;
  • Redox control of heme-protein-dependent NO responses;
  • The interplay between NO and antioxidant systems;
  • NO and redox signaling in cancer biology;
  • The influence of NO on inflammatory redox pathways;
  • The role of NO in redox homeostasis.

Dr. Massimiliano Coletta
Prof. Dr. Paolo Ascenzi
Dr. Giovanna De Simone
Guest Editors

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Keywords

  • nitric oxide
  • ROS and RNS
  • nitrosative stress
  • NO signaling
  • redox mechanisms

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Published Papers (4 papers)

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Research

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19 pages, 3735 KiB  
Article
A Fluorescent Probe for Imaging and Treating S-Nitrosation Stress in OGD/R Cells
by Hui Ye, Chen Zhang, Lerong Li, Cunrui Li, Jiayue Yu, Duorui Ji, Zhuangzhuang Liang, Jianbing Wu and Zhangjian Huang
Antioxidants 2025, 14(3), 311; https://doi.org/10.3390/antiox14030311 - 4 Mar 2025
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Abstract
Protein S-nitrosation, a redox post-translational modification elicited by nitric oxide (NO), is essential for modulating diverse protein functions and signaling pathways. Dysregulation of S-nitrosation is implicated in various pathological processes, including oxygen-glucose deprivation/reperfusion (OGD/R) injury, a widely used model for ischemia-reperfusion diseases. The [...] Read more.
Protein S-nitrosation, a redox post-translational modification elicited by nitric oxide (NO), is essential for modulating diverse protein functions and signaling pathways. Dysregulation of S-nitrosation is implicated in various pathological processes, including oxygen-glucose deprivation/reperfusion (OGD/R) injury, a widely used model for ischemia-reperfusion diseases. The dynamic changes in S-nitrosothiols (SNOs) during ischemia-reperfusion highlight the need for theranostic strategies to monitor and modulate SNO levels based on pathological progression. However, to date, no theranostic strategies have been reported for addressing dysregulated SNO in disease models, particularly in OGD/R conditions. Here, we report the development of a selective probe P-EHC, which could specifically react with SNOs to release EHC, not only exhibiting turn-on fluorescence with high quantum yield and good water solubility but also demonstrating macrophage migration inhibitory factor (MIF) inhibitory activity. In an OGD/R model of SH-SY5Y cells, we observed elevated SNO levels by using live-cell confocal imaging. Treatment of P-EHC significantly reduced intracellular reactive oxygen species (ROS), lowered total NOx species, and improved cell viability in the OGD/R model. In summary, the simplicity and versatility of P-EHC suggest its broad applicability for monitoring SNO in various biological models and therapeutic contexts, particularly in ischemia-reperfusion diseases. Full article
(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)
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12 pages, 1199 KiB  
Article
The Interplay between Nitrosative Stress, Inflammation, and Antioxidant Defense in Patients with Lichen Planus
by Mircea Tampa, Ilinca Nicolae, Corina Daniela Ene, Cristina Iulia Mitran, Madalina Irina Mitran, Clara Matei and Simona Roxana Georgescu
Antioxidants 2024, 13(6), 670; https://doi.org/10.3390/antiox13060670 - 30 May 2024
Cited by 2 | Viewed by 1169
Abstract
Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune [...] Read more.
Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers—direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense. Full article
(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)
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Review

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38 pages, 2181 KiB  
Review
Is Inducible Nitric Oxide Synthase (iNOS) Promising as a New Target Against Pulmonary Hypertension?
by Piotr Ryszkiewicz, Eberhard Schlicker and Barbara Malinowska
Antioxidants 2025, 14(4), 377; https://doi.org/10.3390/antiox14040377 - 21 Mar 2025
Viewed by 443
Abstract
Pulmonary hypertension (PH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, associated also with inflammation and oxidative stress. Inducible nitric oxide synthase (iNOS) is one of the key mediators of inflammation and immune system activation. Although preclinical studies [...] Read more.
Pulmonary hypertension (PH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, associated also with inflammation and oxidative stress. Inducible nitric oxide synthase (iNOS) is one of the key mediators of inflammation and immune system activation. Although preclinical studies mostly suggest a detrimental role of iNOS overactivation in PH, there is a lack of exhaustive analyses and summaries. Therefore, this literature overview aims to fill this gap. The involvement of iNOS in the pathogenesis of the four main clinical groups of PH is discussed to assess whether targeting iNOS could be a promising way to treat PH. iNOS expression patterns in the organs primarily affected by PH are analyzed both in animals and in humans. Consequently, the effectiveness of pharmacological iNOS inhibition and/or iNOS gene deletion is discussed and compared, also with reference to the activity of constitutive NOS isoforms, particularly endothelial NOS (eNOS). Overall, our overview suggests that selective iNOS inhibitors could be considered as a novel treatment strategy for PH, as decreases in right ventricular and pulmonary artery pressure, the alleviation of ventricular hypertrophy, and improvements of pulmonary and cardiac function were observed, among others. Nevertheless, further research efforts in this area are needed. Full article
(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)
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21 pages, 2334 KiB  
Review
Nitric Oxide Binding Geometry in Heme-Proteins: Relevance for Signal Transduction
by Giovanna De Simone, Alessandra di Masi, Diego Sbardella, Paolo Ascenzi and Massimiliano Coletta
Antioxidants 2024, 13(6), 666; https://doi.org/10.3390/antiox13060666 - 29 May 2024
Cited by 1 | Viewed by 1812
Abstract
Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes [...] Read more.
Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes related to the different binding modes of NO to heme-Fe(II), as well as the modulatory effects of this diatomic messenger on heme-protein functions. Specifically, the ability of heme proteins to bind NO at either the distal or proximal side of the heme and the transient interchanging of the binding site is reported. This sheds light on the regulation of O2 supply to tissues with high metabolic activity, such as the retina, where a precise regulation of blood flow is necessary to meet the demand of nutrients. Full article
(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)
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