Redox Proteomics

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

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 6091

Special Issue Editor


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Guest Editor
Center for Neuroscience and Cell Biology, Parque Tecnológico de Cantanhede, University of Coimbra, Núcleo 04, Lote 8, 3060-197 Cantanhede, Portugal
Interests: cysteine oxidation; redox signaling; proteomic screenings; low molecular thiols; cysteine probes

Special Issue Information

Dear Colleagues,

Reactive oxygen/nitrogen species (ROS/NOS) are common by-products of the metabolism, which are associated, not only with deleterious effects and disease development, but also with a physiological role as second messengers in the regulation of several pathways. Among several amino acids, cysteine thiol groups are particularly susceptible to oxidation by those reactive species, with the modifications of these residues being related to modulation of protein function and biological processes. The redox state of cysteine residues can be rapidly and reversibly modified, making the cysteinome a good predictor of the overall cellular state and fate. Although low levels of oxidation are required for cellular functions, both the over-reduction and over-oxidation of the cysteines tends to lead to protein dysfunction and damage, which can be associated with a disease state or even cell death. In this sense, the characterization of the cysteinome can be of extreme importance in understanding the tight regulation between physiological and pathophysiological processes and to provide new targets for therapeutic purposes. 

In this Special Issue, we invite researchers to provide original research articles and review articles related to will the modulation of proteins by cysteine oxidation, including both large proteomics screenings and studies of a single target. Methodological articles focused on new strategies to study cysteine oxidation and works involving the study of low molecular thiols will also be considered. We want to make this Special Issue a valued overview of the developments in the cysteine oxidation field, highlighting its importance to gain new insight into redox signaling regulation

Dr. Sandra Anjo
Guest Editor

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Keywords

  • cysteine oxidation
  • redox signaling
  • redoxome proteomic screenings
  • redox biology
  • low molecular thiols
  • mass spectrometry methods
  • cysteine probes

Published Papers (3 papers)

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Research

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19 pages, 3671 KiB  
Article
BET Protein Inhibitor JQ1 Ameliorates Experimental Peritoneal Damage by Inhibition of Inflammation and Oxidative Stress
by Vanessa Marchant, Flavia Trionfetti, Lucia Tejedor-Santamaria, Sandra Rayego-Mateos, Dante Rotili, Giulio Bontempi, Alessandro Domenici, Paolo Menè, Antonello Mai, Catalina Martín-Cleary, Alberto Ortiz, Adrian M. Ramos, Raffaele Strippoli and Marta Ruiz-Ortega
Antioxidants 2023, 12(12), 2055; https://doi.org/10.3390/antiox12122055 - 29 Nov 2023
Cited by 1 | Viewed by 1028
Abstract
Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to [...] Read more.
Peritoneal dialysis (PD) is a current replacement therapy for end-stage kidney diseases (ESKDs). However, long-term exposure to PD fluids may lead to damage of the peritoneal membrane (PM) through mechanisms involving the activation of the inflammatory response and mesothelial-to-mesenchymal transition (MMT), leading to filtration failure. Peritoneal damage depends on a complex interaction among external stimuli, intrinsic properties of the PM, and subsequent activities of the local innate–adaptive immune system. Epigenetic drugs targeting bromodomain and extra-terminal domain (BET) proteins have shown beneficial effects on different experimental preclinical diseases, mainly by inhibiting proliferative and inflammatory responses. However the effect of BET inhibition on peritoneal damage has not been studied. To this aim, we have evaluated the effects of treatment with the BET inhibitor JQ1 in a mouse model of peritoneal damage induced by chlorhexidine gluconate (CHX). We found that JQ1 ameliorated the CHX-induced PM thickness and inflammatory cell infiltration. Moreover, JQ1 decreased gene overexpression of proinflammatory and profibrotic markers, together with an inhibition of the nuclear factor-κB (NF-κB) pathway. Additionally, JQ1 blocked the activation of nuclear factor erythroid 2-related factor 2 (NRF2) and restored changes in the mRNA expression levels of NADPH oxidases (NOX1 and NOX4) and NRF2/target antioxidant response genes. To corroborate the in vivo findings, we evaluated the effects of the BET inhibitor JQ1 on PD patients’ effluent-derived primary mesothelial cells and on the MeT-5A cell line. JQ1 inhibited tumor necrosis factor-α (TNF-α)-induced proinflammatory gene upregulation and restored MMT phenotype changes, together with the downmodulation of oxidative stress. Taken together, these results suggest that BET inhibitors may be a potential therapeutic option to ameliorate peritoneal damage. Full article
(This article belongs to the Special Issue Redox Proteomics)
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Review

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25 pages, 1229 KiB  
Review
Using Redox Proteomics to Gain New Insights into Neurodegenerative Disease and Protein Modification
by Paula Cadenas-Garrido, Ailén Schonvandt-Alarcos, Lourdes Herrera-Quintana, Héctor Vázquez-Lorente, Alicia Santamaría-Quiles, Jon Ruiz de Francisco, Marina Moya-Escudero, David Martín-Oliva, Sandra M. Martín-Guerrero, César Rodríguez-Santana, Jerónimo Aragón-Vela and Julio Plaza-Diaz
Antioxidants 2024, 13(1), 127; https://doi.org/10.3390/antiox13010127 - 20 Jan 2024
Viewed by 1474
Abstract
Antioxidant defenses in biological systems ensure redox homeostasis, regulating baseline levels of reactive oxygen and nitrogen species (ROS and RNS). Oxidative stress (OS), characterized by a lack of antioxidant defenses or an elevation in ROS and RNS, may cause a modification of biomolecules, [...] Read more.
Antioxidant defenses in biological systems ensure redox homeostasis, regulating baseline levels of reactive oxygen and nitrogen species (ROS and RNS). Oxidative stress (OS), characterized by a lack of antioxidant defenses or an elevation in ROS and RNS, may cause a modification of biomolecules, ROS being primarily absorbed by proteins. As a result of both genome and environment interactions, proteomics provides complete information about a cell’s proteome, which changes continuously. Besides measuring protein expression levels, proteomics can also be used to identify protein modifications, localizations, the effects of added agents, and the interactions between proteins. Several oxidative processes are frequently used to modify proteins post-translationally, including carbonylation, oxidation of amino acid side chains, glycation, or lipid peroxidation, which produces highly reactive alkenals. Reactive alkenals, such as 4-hydroxy-2-nonenal, are added to cysteine (Cys), lysine (Lys), or histidine (His) residues by a Michael addition, and tyrosine (Tyr) residues are nitrated and Cys residues are nitrosylated by a Michael addition. Oxidative and nitrosative stress have been implicated in many neurodegenerative diseases as a result of oxidative damage to the brain, which may be especially vulnerable due to the large consumption of dioxygen. Therefore, the current methods applied for the detection, identification, and quantification in redox proteomics are of great interest. This review describes the main protein modifications classified as chemical reactions. Finally, we discuss the importance of redox proteomics to health and describe the analytical methods used in redox proteomics. Full article
(This article belongs to the Special Issue Redox Proteomics)
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18 pages, 1205 KiB  
Review
The 4-Hydroxynonenal–Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?
by Lidija Milkovic, Neven Zarkovic, Zlatko Marusic, Kamelija Zarkovic and Morana Jaganjac
Antioxidants 2023, 12(4), 856; https://doi.org/10.3390/antiox12040856 - 01 Apr 2023
Cited by 17 | Viewed by 2962
Abstract
It is well known that oxidative stress and lipid peroxidation (LPO) play a role in physiology and pathology. The most studied LPO product with pleiotropic capabilities is 4-hydroxynonenal (4-HNE). It is considered as an important mediator of cellular signaling processes and a second [...] Read more.
It is well known that oxidative stress and lipid peroxidation (LPO) play a role in physiology and pathology. The most studied LPO product with pleiotropic capabilities is 4-hydroxynonenal (4-HNE). It is considered as an important mediator of cellular signaling processes and a second messenger of reactive oxygen species. The effects of 4-HNE are mainly attributed to its adduction with proteins. Whereas the Michael adducts thus formed are preferred in an order of potency of cysteine > histidine > lysine over Schiff base formation, it is not known which proteins are the preferred targets for 4-HNE under what physiological or pathological conditions. In this review, we briefly discuss the methods used to identify 4-HNE–protein adducts, the progress of mass spectrometry in deciphering the specific protein targets, and their biological relevance, focusing on the role of 4-HNE protein adducts in the adaptive response through modulation of the NRF2/KEAP1 pathway and ferroptosis. Full article
(This article belongs to the Special Issue Redox Proteomics)
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