Redox Biochemistry and Chemistry最新文献_第3页

Amplex Red cellular uptake produces radical intermediates by myeloperoxidase and mediates oxidative stress 红细胞摄取通过髓过氧化物酶产生自由基中间体并介导氧化应激

Redox Biochemistry and Chemistry Pub Date : 2025-06-01 Epub Date: 2025-04-15 DOI: 10.1016/j.rbc.2025.100051

Huan Liu , Lusine Tonoyan , Béla Reiz , Arno G. Siraki

{"title":"Amplex Red cellular uptake produces radical intermediates by myeloperoxidase and mediates oxidative stress","authors":"Huan Liu , Lusine Tonoyan , Béla Reiz , Arno G. Siraki","doi":"10.1016/j.rbc.2025.100051","DOIUrl":"10.1016/j.rbc.2025.100051","url":null,"abstract":"<div><div>Amplex Red (AR) is commonly used to detect extracellular hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and is considered a cell-impermeable compound. However, it would appear capable of entering cells based on its phenoxazine substructure and the report of its mitochondrial membrane permeability. Additionally, myeloperoxidase (MPO) oxidation of AR produces a fluorescent compound, resorufin, which has been reported, though the mechanism is not well-studied. EPR spin trapping using glutathione (GSH) revealed that AR metabolism produced AR radicals and glutathionyl radicals (GS<sup>•</sup>). An intermediate metabolite, 3,7-dihydroxyphenoxazine, was observed by liquid chromatography-mass spectrometry (LC-MS), which supported AR radical disproportionation first and subsequently N-oxidation. Besides, in the presence of GSH, the formation of resorufin decreased significantly evidencing the reactivity of radical intermediates. Three types of AR-GS adduct were found using LC-MS and the resorufin GS-adduct was the dominant one. Regarding intracellular findings in HL-60 cells (that highly express MPO), LC-MS and fluorescence analysis showed AR penetrated the cell membrane and was oxidized by cellular MPO. Interestingly, we demonstrated that the oxidation of AR in HL-60 cells showed a significant time dependence; PF-1355, an MPO inhibitor, inhibited the oxidation of AR by MPO. Cell viability (ATP) revealed that 200 μM AR significantly decreased viability in HL-60 cells in 6 h. We also found that AR-mediated decreased total GSH and increased protein-radical formation. These findings revealed that AR is cell-permeable, and AR radicals induce cellular oxidative distress and lead to the formation of protein radicals, which correlate with the MPO-mediated mechanism of cytotoxicity.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"12 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851843","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}

引用次数: 0

Corrigendum to “Hypochlorous acid inactivates myeloperoxidase inside phagocytosing neutrophils” [Redox Biochem. Chem. 5–6 (2023) 100008] “次氯酸使吞噬中性粒细胞内的髓过氧化物酶失活”的勘误表[氧化还原生化]。化学。5-6 (2023)100008]

Redox Biochemistry and Chemistry Pub Date : 2025-06-01 Epub Date: 2025-05-21 DOI: 10.1016/j.rbc.2025.100053

Martina Paumann-Page , Louisa V. Ashby , Irada Khalilova , Nicholas J. Magon , Stefan Hofbauer , Louise N. Paton , Paul G. Furtmüller , Christian Obinger , Anthony J. Kettle

引用次数: 0

Enzymes of glycolysis and the pentose phosphate pathway as targets of oxidants: Role of redox reactions on the carbohydrate catabolism 糖酵解酶和戊糖磷酸途径作为氧化剂的目标：氧化还原反应在碳水化合物分解代谢中的作用

Redox Biochemistry and Chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-18 DOI: 10.1016/j.rbc.2025.100049

Eduardo Fuentes-Lemus , Karen Usgame , Angélica Fierro , Camilo López-Alarcón

{"title":"Enzymes of glycolysis and the pentose phosphate pathway as targets of oxidants: Role of redox reactions on the carbohydrate catabolism","authors":"Eduardo Fuentes-Lemus , Karen Usgame , Angélica Fierro , Camilo López-Alarcón","doi":"10.1016/j.rbc.2025.100049","DOIUrl":"10.1016/j.rbc.2025.100049","url":null,"abstract":"<div><div>Redox reactions can modulate metabolic and signaling pathways with consequences on cellular adaptation to different stimuli. The abundance and structural features of some metabolic enzymes make these targets of oxidants, including one- and two-electron oxidant molecules, altering their structure and/or function. Therefore, redox processes play an important role in physiology and pathology. In particular, the oxidative post-translational modification of the enzymes that participate in glycolysis and the pentose phosphate pathway (PPP) can modulate the carbon flux affecting synthesis of nucleotides, as well as production of adenosine triphosphate (ATP) and reducing equivalents (in the form of nicotinamide adenine dinucleotide phosphate, NADPH). Specifically, generation of NADPH, a cofactor important for cell homeostasis, is key to the management of the redox status of cells towards oxidative insults. In this review we discuss the available literature on the impact of oxidative post-translational modifications on key glycolytic and PPP enzymes with an analysis of the consequences these may have for cell metabolic adaptation. We also discuss the contributions of new experimental and <em>in silico</em> approaches to the redox biochemistry field, which have significantly illuminated the intricate relationship between the pathways involved in carbohydrate metabolism and how these could be regulated by redox reactions.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100049"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Formation of protein-derived electrophiles in ribonuclease A by biologically relevant oxidants 生物相关氧化剂在核糖核酸酶A中形成蛋白质衍生的亲电试剂

Redox Biochemistry and Chemistry Pub Date : 2025-03-01 Epub Date: 2025-02-07 DOI: 10.1016/j.rbc.2025.100048

Ana C. Lopez , Silvina Acosta , Mauricio Mastrogiovanni , Williams Porcal , María Magdalena Portela , Rosario Durán , Rafael Radi , Ana Denicola , Matias N. Möller

{"title":"Formation of protein-derived electrophiles in ribonuclease A by biologically relevant oxidants","authors":"Ana C. Lopez , Silvina Acosta , Mauricio Mastrogiovanni , Williams Porcal , María Magdalena Portela , Rosario Durán , Rafael Radi , Ana Denicola , Matias N. Möller","doi":"10.1016/j.rbc.2025.100048","DOIUrl":"10.1016/j.rbc.2025.100048","url":null,"abstract":"<div><div>Oxidative modifications in proteins have been extensively studied and found to increase in diabetes, cardiovascular diseases, neurodegenerative diseases, and aging. Some of the most studied modifications include the nitration of tyrosine and the formation of carbonyls in proteins. Tyrosine can also be oxidized to 3-(1-hydroxy-4-oxocyclohexa-2,5-dien-1-yl)-L-alanine (HOCHDA) by several biologically relevant systems, a product that is electrophilic and reactive to biological nucleophiles such as glutathione. Herein, we characterized the reaction of a peptide containing HOCHDA with fluorescein-tagged glutathione by HPLC and mass spectrometry. To explore the possibility that the formation of oxidation-derived electrophiles occurs in proteins, we oxidized the tyrosine-rich, small protein, ribonuclease A, by different biologically relevant oxidizing systems and used fluorescein-tagged glutathione as the nucleophilic reagent. Oxidation of ribonuclease A with singlet oxygen, known to generate HOCHDA efficiently, generated an electrophile that reacted with fluorescein-tagged glutathione and was resistant to reduction by dithiothreitol. The amount of fluorescein-glutathione attached to the protein was quantified by gel filtration HPLC. Other oxidants such as peroxyl radical (from AAPH), ferryl (from hydrogen peroxide reaction with Fe(II):EDTA), and peroxynitrite, also generated a modified protein that reacted with fluorescein-glutathione. Analysis by LC-MS/MS indicated the formation of mono-oxygenated tyrosyl residues and di-oxygenated histidyl residues after exposure of the protein to AAPH which are good candidates to be the electrophilic centers. The formation of electrophiles was a common feature in the reactions of oxidants with ribonuclease A and may constitute an underappreciated mechanism of protein oxidative modification.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100048"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Properties of disulfide radical anions and their reactions in chemistry and biology 二硫自由基阴离子的性质及其在化学和生物学中的反应

Redox Biochemistry and Chemistry Pub Date : 2025-03-01 Epub Date: 2024-12-05 DOI: 10.1016/j.rbc.2024.100046

Chryssostomos Chatgilialoglu , Bronisław Marciniak , Krzysztof Bobrowski

{"title":"Properties of disulfide radical anions and their reactions in chemistry and biology","authors":"Chryssostomos Chatgilialoglu , Bronisław Marciniak , Krzysztof Bobrowski","doi":"10.1016/j.rbc.2024.100046","DOIUrl":"10.1016/j.rbc.2024.100046","url":null,"abstract":"<div><div>Disulfide radical anions (RSSR<sup>•−</sup>) derive both from the direct electron attachment to disulfide-containing compounds and the reaction of thiyl radicals with thiolate, being also reversible (RS<sup>•</sup> + RS<sup>−</sup> ⇆ RSSR<sup>•−</sup>). The investigation of these reactive intermediates started in 1960s by pulse radiolysis (PR) technique and electron spin resonance (ESR) spectroscopy, and more recently, their generation was studied in organic chemistry and biological mechanisms. The present review addresses a compendium on structural, chemical and spectroscopical properties of disulfide radical anions, as well as their involvement in synthetical and biological processes. Particular emphasis is given to disulfide moieties as reactive sites in proteins, and to the generation of small sulfur-centered radicals, connected to the discovery of a mechanism of tandem protein-lipid damage. Other important biologically related processes involving disulfide radical anions are treated in the review, such as: its formation from the glutathione thiyl radical GS<sup>•</sup> (GS<sup>•</sup> + GS<sup>−</sup> ⇆ GSSG<sup>•−</sup>), resulting from the antioxidant reactivity of glutathione (GSH/GS<sup>–</sup>), and the reduction of a ketone moiety by the disulfide radical anion at the active site of the enzymes ribonucleotide reductase (RNRs), the latter used for establishing a bioinspired reduction process in organic synthesis.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"11 ","pages":"Article 100046"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Small molecule probes for peroxynitrite detection 用于检测过亚硝酸盐的小分子探针

Redox Biochemistry and Chemistry Pub Date : 2024-12-01 Epub Date: 2024-07-26 DOI: 10.1016/j.rbc.2024.100034

Aleksandra Grzelakowska , Balaraman Kalyanaraman , Jacek Zielonka

{"title":"Small molecule probes for peroxynitrite detection","authors":"Aleksandra Grzelakowska , Balaraman Kalyanaraman , Jacek Zielonka","doi":"10.1016/j.rbc.2024.100034","DOIUrl":"10.1016/j.rbc.2024.100034","url":null,"abstract":"<div><p>Peroxynitrite (ONOO<sup>−</sup>/ONOOH) is a short-lived but highly reactive species that is formed in the diffusion-controlled reaction between nitric oxide and the superoxide radical anion. It can oxidize certain biomolecules and has been considered as a key cellular oxidant formed under various pathophysiological conditions. It is crucial to selectively detect and quantify ONOO<sup>−</sup> to determine its role in biological processes. In this review, we discuss various approaches used to detect ONOO<sup>−</sup> in cell-free and cellular systems with the major emphasis on small-molecule chemical probes. We review the chemical principles and mechanisms responsible for the formation of the detectable products, and plausible limitations of the probes. We recommend the use of boronate-based chemical probes for ONOO<sup>−</sup>, as they react directly and rapidly with ONOO<sup>−</sup>, they produce minor but ONOO<sup>−</sup>‒specific products, and the reaction kinetics and mechanism have been rigorously characterized. Specific experimental approaches and protocols for the detection of ONOO<sup>−</sup> in cell-free, cellular, and <em>in vivo</em> systems using boronate-based molecular probes are provided (as shown in Boxes 1-6).</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100034"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000154/pdfft?md5=a4723535d75e5476ac6136a1e8cdeac7&pid=1-s2.0-S2773176624000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reaction of peroxynitrite with thiols, hydrogen sulfide and persulfides 过亚硝酸与硫醇、硫化氢和过硫化物的反应

Redox Biochemistry and Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-08 DOI: 10.1016/j.rbc.2024.100039

Madia Trujillo , Ernesto Cuevasanta , Lucía Turell , Dayana Benchoam , Gerardo Ferrer-Sueta , Ari Zeida , Celia Quijano , Sebastián Carballal , Rafael Radi , Beatriz Alvarez

{"title":"Reaction of peroxynitrite with thiols, hydrogen sulfide and persulfides","authors":"Madia Trujillo , Ernesto Cuevasanta , Lucía Turell , Dayana Benchoam , Gerardo Ferrer-Sueta , Ari Zeida , Celia Quijano , Sebastián Carballal , Rafael Radi , Beatriz Alvarez","doi":"10.1016/j.rbc.2024.100039","DOIUrl":"10.1016/j.rbc.2024.100039","url":null,"abstract":"<div><p>Three decades of research on the biochemistry of peroxynitrite (ONOOH/ONOO<sup>−</sup>) have established that this stealthy oxidant is formed in biological systems, and that its main targets are carbon dioxide (CO<sub>2</sub>), metalloproteins and thiols (RSH). Peroxynitrous acid reacts directly with thiols (precisely, with thiolates, RS<sup>−</sup>), forming sulfenic acids (RSOH). In addition, the free radicals derived from peroxynitrite, mainly carbonate radical anion (<span><math><msup><msub><mi>CO</mi><mn>3</mn></msub><mrow><mo>•</mo><mo>−</mo></mrow></msup></math></span>) and nitrogen dioxide (<span><math><msup><msub><mi>NO</mi><mn>2</mn></msub><mrow><mo>•</mo></mrow></msup></math></span>) formed from the reaction of peroxynitrite anion with CO<sub>2</sub>, oxidize thiols to thiyl radicals (RS<sup>•</sup>). These two pathways are under kinetic competition. The primary products of thiol oxidation can follow different decay routes; sulfenic acids usually react with other thiols forming disulfides, while thiyl radicals can react with oxygen, with other thiols and with other reductants such as ascorbic acid. Peroxynitrite is also able to oxidize hydrogen sulfide (H<sub>2</sub>S/HS<sup>−</sup>) and persulfides (RSSH/RSS<sup>−</sup>). Among the different biological thiols, peroxiredoxins stand out as main peroxynitrite reductases due to their very high rate constants of reaction with peroxynitrite together with their abundance. Rooted in kinetic concepts, evidence is emerging for the role of peroxiredoxins in peroxynitrite detoxification, with potential implications in diseases in which peroxynitrite is involved.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100039"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000208/pdfft?md5=d3ba6f796dbd6aef9cd2c5262abce81f&pid=1-s2.0-S2773176624000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxynitrite: A tale of two radicals 亚硝酸过氧化物两个自由基的故事

Redox Biochemistry and Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-03 DOI: 10.1016/j.rbc.2024.100038

Patricia L. Bounds , Willem H. Koppenol

引用次数: 0

Perceptions of peroxynitrite reactivity – Then and now 对过氧化亚硝酸盐反应性的认识--过去和现在

Redox Biochemistry and Chemistry Pub Date : 2024-12-01 Epub Date: 2024-08-20 DOI: 10.1016/j.rbc.2024.100041

Sergei V. Lymar , James K. Hurst

{"title":"Perceptions of peroxynitrite reactivity – Then and now","authors":"Sergei V. Lymar , James K. Hurst","doi":"10.1016/j.rbc.2024.100041","DOIUrl":"10.1016/j.rbc.2024.100041","url":null,"abstract":"<div><div>Many chemical and biological reactions involving peroxynitrite<span><span><sup>3</sup></span></span> occur by unusual rate laws that are independent of the identity of the reacting partner. The true nature of these reactions and the identities of actual reactive species have been the subject of considerable debate ever since the notion that peroxynitrite is an important component of oxidative stress was first introduced in the early 1990s. We present herein a succinct historical review of this topic written from the perspective that intermediary inorganic free radicals are the causative agents in these reactions. This viewpoint provides a complete self-consistent rationalization of all verified data from multiple laboratories, whereas other explanations have been unable to do so. Recognition of the radical nature of peroxynitrite decomposition has also allowed a reassessment of the quantitative mechanism of CO<sub>2</sub>-catalyzed peroxynitrite decomposition. Detailed analyses indicate that the constant for rate-limiting formation of the putative reactive carbon dioxide adduct (<span><math><msup><mrow><msub><mtext>ONOOCO</mtext><mn>2</mn></msub></mrow><mo>−</mo></msup></math></span>)<span><span><sup>3</sup></span></span> is actually ∼20% less than previously recognized and CO<sub>2</sub> turnover numbers for catalysis (that is, the number of reaction cycles that CO<sub>2</sub> undergoes before being removed as bicarbonate) are relatively large and dependent upon the [CO<sub>2</sub>]/[ONOO<sup>−</sup>] ratio in the reaction environment.</div></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"10 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial: Special issue celebrating the work of Prof. Christine C. Winterbourn 社论：特刊庆祝克里斯汀C.温特伯恩教授的工作

Redox Biochemistry and Chemistry Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1016/j.rbc.2024.100045

Michael J. Davies (Joint Editor-in-Chief), Rafael Radi (Joint Editor-in-Chief)

引用次数: 0