Redox Biochemistry and Chemistry最新文献

{"title":"Making sense of subcellular H2O2 in mammals","authors":"Markus Waldeck-Weiermair ,&nbsp;Taylor A. Covington ,&nbsp;Arvind K. Pandey ,&nbsp;Thomas Michel","doi":"10.1016/j.rbc.2026.100080","DOIUrl":"10.1016/j.rbc.2026.100080","url":null,"abstract":"<div><div>Hydrogen peroxide (H₂O₂) is a non-radical reactive oxygen species (ROS) that plays a crucial role in maintaining physiological cellular functions. Acting as a redox signaling molecule, H₂O₂ selectively oxidizes reactive thiol groups of protein cysteines, enabling dynamic regulation of protein function through reversible redox modifications. These redox-sensitive modulations are tightly controlled by compartmentalized oxidoreductase systems, which continuously maintain a balance between H₂O₂ production from endogenous sources such as NADPH oxidases and mitochondria, and its elimination by compartment-specific antioxidant enzymes. Importantly, intracellular H₂O₂ concentrations are highly heterogeneous and vary across subcellular locales, reflecting distinct redox environments and organelle-specific functional demands within the cell. Physiological, compartment-specific regulation of H₂O₂ supports redox signaling and adaptive metabolic responses, whereas disruption of spatially confined H₂O₂ homeostasis results in localized oxidative distress that contributes to cellular dysfunction and disease. Recent advances in genetically encoded biosensors, particularly improved roGFP- and HyPer-based designs, have enabled sensitive, real-time detection of subcellular H₂O₂ dynamics in living cells. These tools provide unprecedented insight into localized oxidative signaling and the spatial organization of redox stress under both physiological and pathological conditions. In this review, we summarize current strategies for monitoring H₂O₂ dynamics using genetically engineered biosensors, with a focus on compartment-specific H₂O₂ homeostasis in health and disease.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"16 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148184282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of the peptide bond and the presence of tryptophan on the photogeneration and photochemical properties of dityrosine","authors":"Karla P. García Beltrán ,&nbsp;Gemma M. Rodríguez-Muñiz ,&nbsp;Virginie Lhiaubet-Vallet ,&nbsp;Andrés H. Thomas ,&nbsp;M. Laura Dántola","doi":"10.1016/j.rbc.2025.100067","DOIUrl":"10.1016/j.rbc.2025.100067","url":null,"abstract":"<div><div>3,3′-Dityrosine, resulting from the formation of a carbon-carbon bond between two tyrosines (Tyr), is one of the most important modifications of the oxidatively generated damage to proteins. Its formation can induce structural changes in proteins, leading to the loss of their biological function. Interestingly, under UVA radiation, dityrosine can also act as an intrinsic photosensitizer that generates reactive oxygen species and induces chemical modifications in amino acids. Despite the biomedical importance of dityrosine, the information regarding its photosensitized generation and photochemical properties is limited due to the drawbacks inherent to its synthesis. In this work we studied the photosensitized formation of dityrosine, in the absence and presence of tryptophan (Trp), using pterin (Ptr) as endogenous type I sensitizer. Free Tyr and Tyr incorporated into specially designed peptides were used as target molecules. Our results indicate that the efficiency of dimerization is not affected by the presence of the peptide bond. Nonetheless, incorporation of dityrosine into a peptide chain appears to confer a certain degree of protection, making it more resistant to photosensitized degradation. Moreover, we demonstrated that, within a peptide chain, an adjacent Trp residue promotes the photoinduced dimerization of Tyr, likely due to electron transfer from the Tyr residue to the oxidized Trp. This effect is not observed when the two residues are more distant. Additionally, the presence of free Trp or Trp within the same peptide chain enhances the efficiency of the photosensitized degradation of the free and peptide dityrosine, respectively.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uratylated albumin activates endothelial cells to induce monocyte adhesion and the release of pro-inflammatory cytokines","authors":"Railmara Pereira da Silva ,&nbsp;Beatriz Pereira da Silva ,&nbsp;Antônio Paulo Siqueira Pratti ,&nbsp;Bianca Dempsey ,&nbsp;Caroline Dutra Lacerda ,&nbsp;Gustavo Penteado Battesini Carretero ,&nbsp;Álbert Souza Peixoto ,&nbsp;Litiele Cezar Cruz ,&nbsp;Camilla Adan ,&nbsp;Iolanda Midea Cuccovia ,&nbsp;Flavia Carla Meotti","doi":"10.1016/j.rbc.2026.100071","DOIUrl":"10.1016/j.rbc.2026.100071","url":null,"abstract":"<div><div>Albumin, the most abundant serum protein in mammals, is critical for transporting low-water-soluble metabolites, ions, and xenobiotics, as well as maintaining osmotic balance. This protein is highly susceptible to post-translational modifications, which can alter its structure and function. Reactive oxygen species (ROS) play a significant role in inducing such modifications, leading to protein dysfunction and contributing to inflammatory and cardiovascular pathologies. Previous studies have demonstrated a link between uric acid (UA) oxidation products, particularly urate hydroperoxide (HOOU), and albumin modifications through a process termed uratylation. These albumin adducts result from the addition of a 140 Da product mass predominantly on lysine and amine from N-terminal residues. Therefore, the aim of this study was to investigate the structural and functional consequences of uratylation on albumin and its effects on endothelial cells. Uratylation promotes a decrease in enthalpy change of denaturation of albumin and binding of Anilino-Naphthalene-Sulfonic acid (ANS), suggesting slight changes in protein structure. Uratylated albumin reduced human umbilical vein endothelial cell (HUVEC) migration, increased intercellular adhesion molecule-1 (ICAM-1) expression and, consequently, monocyte adhesion (THP-1), indicating endothelial activation. Furthermore, the presence of uratylated albumin stimulated the release of tumor necrosis factor-α (TNF-α). These findings provide novel insights into the mechanistic pathways connecting uric acid oxidation, post-translational modification on albumin and inflammation, highlighting the potential role of uratylated albumin in endothelial dysfunction and atherogenesis.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo studies of redox biochemistry in vertebrate tissues - present successes and future horizons","authors":"Lev L. Naumov ,&nbsp;Anastasia D. Sergeeva ,&nbsp;Veronika A. Katrukha ,&nbsp;Alexander I. Kostyuk ,&nbsp;Nadezda A. Brazhe ,&nbsp;Dmitry S. Bilan ,&nbsp;Yulia V. Khramova","doi":"10.1016/j.rbc.2025.100069","DOIUrl":"10.1016/j.rbc.2025.100069","url":null,"abstract":"<div><div>Over the past decades, the field of redox biology has witnessed a profound expansion in the catalog of known redox-active compounds, revealing their critical roles in cellular signaling and homeostasis. Paralleling this discovery, the toolbox of genetically encoded fluorescent indicators (GEFIs) has evolved to enable real-time, specific monitoring of these molecules within living cells. This review synthesizes key studies employing GEFIs to investigate redox dynamics in vertebrate models, covering a spectrum of physiological and pathophysiological contexts. A critical analysis of the architectural designs, operational mechanisms, and performance parameters—including advantages and inherent limitations—of prominent GEFIs is provided. Finally, we explore the constraints of traditional fluorescence imaging methodologies in complex <em>in vivo</em> settings and consider label-free methods for detecting redox events using Raman spectroscopy, FLIM.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145842805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detecting oxidants in muscle in vivo: A perspective on “State of the art in vivo reactive oxygen species measurements in skeletal muscle using fluorescent probes”","authors":"Malcolm J. Jackson","doi":"10.1016/j.rbc.2026.100073","DOIUrl":"10.1016/j.rbc.2026.100073","url":null,"abstract":"","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100073"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating real time intracellular redox toxicology using live-cell imaging approaches","authors":"Edward R. Pennington ,&nbsp;Emma Kinerson ,&nbsp;Syed Masood ,&nbsp;Elizabeth M. Corteselli ,&nbsp;James M. Samet","doi":"10.1016/j.rbc.2026.100070","DOIUrl":"10.1016/j.rbc.2026.100070","url":null,"abstract":"<div><div>Intracellular oxidative stress is a common mechanism of cellular dysregulation as a result of supraphysiological levels of reactive oxygen species (ROS). Imbalances in redox homeostasis underly adverse responses arising from exposure to a wide variety of xenobiotics and environmental exposures. Observing oxidative cellular events in real time poses multiple analytical challenges, requiring sensitive and specific methodologies that are capable of detecting transient events with high spatiotemporal resolution. We review here the advantages that live-cell imaging offers as a non-destructive approach that is well suited for redox toxicology studies. The effectiveness of this approach is heavily reliant on the use of fluorescent redox sensitive probes, such as small molecule and genetically encoded sensors that report on specific ROS and redox couples. We discuss a variety of small molecule and genetically encoded sensors that are used in redox toxicology, as well as the caveats and limitations posed by their use.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary phenolic compounds as modulators of AGEs-induced photo-oxidation: A focus on the skin and eye lens","authors":"Felipe Ávila ,&nbsp;Denis Fuentealba ,&nbsp;Francisca Muñoz ,&nbsp;Alejandra San Martin ,&nbsp;Bertrand Friguet","doi":"10.1016/j.rbc.2025.100068","DOIUrl":"10.1016/j.rbc.2025.100068","url":null,"abstract":"<div><div>Advanced glycation end products (AGEs) are irreversible products formed when long-lived proteins undergo non-enzymatic reactions with reducing sugars or reactive metabolites. These products resist proteolytic degradation and therefore accumulate with age. Some AGEs act as chromophores, absorbing UVA-visible light and initiating photosensitized oxidation, a process implicated in photoaging of tissues such as the eye lens and skin. Dietary polyphenols, known for their antioxidant and antiglycation effects, may also modulate AGE-mediated photosensitized reactions, although this remains poorly understood. This article discusses the mechanisms through which AGEs contribute to photo-oxidative damage in light-exposed tissues and discusses the potential of dietary polyphenols to modulate these photo-induced processes.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"15 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic identification of protein radicals from myeloperoxidase-mediated mefenamic acid oxidation reveals a mechanism of NSAID-induced oxidative injury","authors":"Newton H. Tran ,&nbsp;Steven Lockhart ,&nbsp;Othman Eldalal ,&nbsp;Phuong G. Tran ,&nbsp;John-Paul R. Cooper ,&nbsp;Lusine Tonoyan ,&nbsp;Richard P. Fahlman ,&nbsp;Arno G. Siraki","doi":"10.1016/j.rbc.2025.100066","DOIUrl":"10.1016/j.rbc.2025.100066","url":null,"abstract":"<div><div>Mefenamic acid (MFA; Ponstel®, USA) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat inflammatory pain. Despite its effectiveness, it carries an FDA black box warning for serious adverse effects, including hepatotoxicity, agranulocytosis, and gastrointestinal injury. While these toxicities are often linked to oxidative distress, the molecular mechanisms remain poorly understood. A key interaction occurs between MFA and myeloperoxidase (MPO), a heme enzyme released from activated neutrophils during inflammation. MPO catalyzes MFA's one-electron oxidation, forming reactive metabolites that modify cellular macromolecules and potentially induce oxidative stress and immune-mediated cytotoxicity. This study examined whether MPO-mediated metabolism of MFA contributes to oxidative damage and cell death in HL-60 promyelocytic leukemia cells. Using compartment-specific spin probes and EPR spectroscopy, MFA was found to increase oxidant production in both cytosolic and mitochondrial compartments. MFA also caused an 80 % loss of mitochondrial membrane potential, activated the Nrf2 antioxidant response, and suppressed phospho-ERK1/2 signaling—changes significantly reversed by PF-1355, a selective MPO inhibitor. Immuno-spin trapping revealed a 133-fold increase in protein-centered radicals following MFA exposure, which was reduced by 97 % with MPO inhibition. Proteomic analysis identified MPO and HSPD1 among the most significantly modified proteins. These findings provide mechanistic insight that MPO-mediated oxidation of MFA generates reactive protein-free radicals, which disrupt redox signaling and protein integrity—ultimately contributing to mitochondrial dysfunction, oxidative stress, and cytotoxicity under inflammatory conditions. This mechanism provides insight into NSAID-induced oxidative injury and supports targeting MPO to improve drug safety under inflammatory conditions.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"14 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145578887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deacetylation of SOD3 by sirtuins restores furin cleavage","authors":"Emily C. Mitchem ,&nbsp;Peter S. Harris ,&nbsp;Cole R. Michel ,&nbsp;Courtney D. McGinnis ,&nbsp;Shashikant Ray ,&nbsp;Krishna M.G. Mallela ,&nbsp;James R. Roede ,&nbsp;Steen V. Petersen ,&nbsp;Eva S. Nozik ,&nbsp;Kristofer S. Fritz","doi":"10.1016/j.rbc.2025.100062","DOIUrl":"10.1016/j.rbc.2025.100062","url":null,"abstract":"<div><div>Accumulation of superoxide radicals leads to disrupted redox signaling and oxidative damage. The primary extracellular scavenger of superoxide is extracellular superoxide dismutase (SOD3), a crucial enzyme in maintaining antioxidant status and proper immune function. SOD3 distribution to the extracellular matrix is determined by the presence of a C-terminal heparin-binding domain (HBD). This region can be removed through intracellular proteolytic processing by furin. Cleavage of the HBD has been shown to be modulated by post-translational cysteine redox status, regulating the secretion of SOD3. Interestingly, other members of the SOD family, SOD1 and SOD2, are known to be inhibited by lysine acetylation, a metabolically linked post-translational modification (PTM) that can alter protein structure, function, and localization. Yet, no reports describe the effect of acetylation on SOD3. Here, immunoblotting and mass spectrometry (MS) were used to quantify the global and site-specific acetylation of recombinant human SOD3. Interestingly, a predicted and targeted parallel reaction monitoring (PRM) MS-based approach was necessary to identify lysine acetylation within the C-terminal HBD of SOD3. Acetylation was found to prevent furin cleavage with no impact on SOD3 activity. Our results also reveal that SOD3 is robustly deacetylated by NAD⁺-dependent sirtuins (SIRT1 and SIRT3), with moderate activity against K220 and high activity against K211 and K212 in the HBD furin cleavage region. These sites of acetylation have not been previously reported, likely due to the peptide's unique hydrophilic nature. Overall, our findings reveal that sirtuin-directed deacetylation of SOD3 restored furin cleavage, defining an important link between redox homeostasis and acetylation-directed metabolic regulation of extracellular oxidative stress.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"14 ","pages":"Article 100062"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145364170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of P450-derived epoxy fatty acids in cardiovascular diseases","authors":"Matthew L. Edin,&nbsp;Joan P. Graves,&nbsp;Darryl C. Zeldin","doi":"10.1016/j.rbc.2025.100064","DOIUrl":"10.1016/j.rbc.2025.100064","url":null,"abstract":"<div><div>The cytochrome P450 (P450 or CYP) superfamily, while extensively recognized for xenobiotic metabolism, is also critically involved in the biosynthesis of lipid mediators from polyunsaturated fatty acids (PUFAs). Distinct from cyclooxygenase (COX) and lipoxygenase (LOX) pathways, P450 enzymes uniquely catalyze the metabolism of PUFAs such as arachidonic acid (AA), to epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) and mid-chain or ω-terminal hydroxyeicosatrienoic acids (HETEs). Eicosanoid biosynthesis is initiated by phospholipase A₂ (PLA₂)-mediated release of PUFAs from cellular membranes. Members of the CYP1-CYP4 subfamilies, including prominent human isoforms like CYP2C8, CYP2C9, and CYP2J2, exhibit significant epoxygenase activity, yielding regio- and stereo-specific EETs. These P450-derived oxylipins exert diverse physiological effects, influencing critical processes such as vascular tone, inflammation, angiogenesis, and ischemia-reperfusion injury. Their biological actions are often modulated by soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH), which hydrolyze EETs to less active dihydroxyeicosatrienoic acids (DHETs). Furthermore, P450s metabolize other PUFAs, including linoleic acid (LA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), generating distinct EpFAs with varying biological effects. Understanding the complex interplay of P450 isoforms, their substrate preferences, and the subsequent metabolic fates of their products is crucial for elucidating their functional roles in health and disease.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"14 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}