Pub Date : 2023-07-14DOI: 10.1016/j.rbc.2023.100006
Alexander V. Peskin
It has been established that hydrogen peroxide (H2O2) acts as a signalling messenger by triggering the reversible oxidation of redox-regulated proteins via a redox-relay provided by peroxiredoxins (Prdxs). Exceptionally high reactivity of Prdxs with H2O2 exceeding other thiols by orders of magnitude places Prdxs as sensors of H2O2 and distributers of oxidizing equivalents to specific thiol targets which can't be oxidized by H2O2 directly. By this mechanism the oxidative stress response can be achieved.
Despite its involvement in oxidative stress responses, H2O2 is continuously generated as a normal metabolite necessary for regular cell functioning. The challenge lies in understanding how the Prdx-dependent redox relay can differentiate between basal levels of H2O2 and excessive amounts that lead to oxidative stress.
Peroxymonocarbonate, an oxidant formed when H2O2 reacts with CO2/HCO3−, emerges as a potent cellular oxidant. The peroxymonocarbonate formation could be catalysed and then consumed at localised sites by certain thiol proteins. This mechanism could prevent H2O2 from reacting with Prdx, thereby averting the redox-relayed activation of regulatory thiol proteins and subsequent oxidative stress response below a certain level of H2O2.
{"title":"Could CO2 be a player in a redox relay team?","authors":"Alexander V. Peskin","doi":"10.1016/j.rbc.2023.100006","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100006","url":null,"abstract":"<div><p>It has been established that hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) acts as a signalling messenger by triggering the reversible oxidation of redox-regulated proteins via a redox-relay provided by peroxiredoxins (Prdxs). Exceptionally high reactivity of Prdxs with H<sub>2</sub>O<sub>2</sub> exceeding other thiols by orders of magnitude places Prdxs as sensors of H<sub>2</sub>O<sub>2</sub> and distributers of oxidizing equivalents to specific thiol targets which can't be oxidized by H<sub>2</sub>O<sub>2</sub> directly. By this mechanism the oxidative stress response can be achieved.</p><p>Despite its involvement in oxidative stress responses, H<sub>2</sub>O<sub>2</sub> is continuously generated as a normal metabolite necessary for regular cell functioning. The challenge lies in understanding how the Prdx-dependent redox relay can differentiate between basal levels of H<sub>2</sub>O<sub>2</sub> and excessive amounts that lead to oxidative stress.</p><p>Peroxymonocarbonate, an oxidant formed when H<sub>2</sub>O<sub>2</sub> reacts with CO<sub>2</sub>/HCO<sub>3</sub><sup>−</sup>, emerges as a potent cellular oxidant. The peroxymonocarbonate formation could be catalysed and then consumed at localised sites by certain thiol proteins. This mechanism could prevent H<sub>2</sub>O<sub>2</sub> from reacting with Prdx, thereby averting the redox-relayed activation of regulatory thiol proteins and subsequent oxidative stress response below a certain level of H<sub>2</sub>O<sub>2</sub>.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726774","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}
Pub Date : 2023-07-01DOI: 10.1016/j.rbc.2023.100003
Kailash Manda , Kei Ohkubo , Yoshimi Shoji , A. K. M. Raushan Kabir Zoardar , Masato Kamibayashi , Toshihiko Ozawa , Kazunori Anzai , Ikuo Nakanishi
Melatonin (N-acetyl-5-methoxytryptamine, MLT), an evolutionarily conserved indoleamine, is known to act as an antioxidant. However, the evidence indicating the role of MLT as a powerful chain-breaking antioxidant by scavenging peroxyl radical remains controversial. The radical-scavenging rate of MLT determined in this study in methanol using galvinoxyl radical (GO•) was much lower than that of an α-tocopherol model compound. The acceleration of the GO•-scavenging reaction by MLT was observed in the presence of magnesium ion (Mg2+), a bio-related redox-inactive metal ion, suggesting that this reaction may proceed via a rate-determining electron transfer followed by proton transfer. The coordination of Mg2+ to the carbonyl oxygen in the one-electron reduced species of GO• (GO–) may stabilize the product, resulting in the acceleration of the electron-transfer process. We also demonstrated that prophylactically administrated MLT efficiently inhibited the lipid peroxide-derived protein modification, which can be detected by a sensitive marker, Nε-(hexanoyl)lysine adduct, in the plasma of X-irradiated mice. The relatively weak GO•-scavenging activity of MLT suggests that the ameliorative effect of MLT against in vivo lipid peroxidation does not result from the direct scavenging of lipid peroxyl radicals by MLT. Therefore, the observed superior protective efficiency of MLT against in vivo lipid peroxidation may partly support the earlier studies, which reported the synergistic antioxidative effect of the metabolites of MLT.
{"title":"In vitro radical-scavenging mechanism of melatonin and its in vivo protective effect against radiation-induced lipid peroxidation","authors":"Kailash Manda , Kei Ohkubo , Yoshimi Shoji , A. K. M. Raushan Kabir Zoardar , Masato Kamibayashi , Toshihiko Ozawa , Kazunori Anzai , Ikuo Nakanishi","doi":"10.1016/j.rbc.2023.100003","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100003","url":null,"abstract":"<div><p>Melatonin (<em>N</em>-acetyl-5-methoxytryptamine, MLT), an evolutionarily conserved indoleamine, is known to act as an antioxidant. However, the evidence indicating the role of MLT as a powerful chain-breaking antioxidant by scavenging peroxyl radical remains controversial. The radical-scavenging rate of MLT determined in this study in methanol using galvinoxyl radical (GO<sup>•</sup>) was much lower than that of an α-tocopherol model compound. The acceleration of the GO<sup>•</sup>-scavenging reaction by MLT was observed in the presence of magnesium ion (Mg<sup>2+</sup>), a bio-related redox-inactive metal ion, suggesting that this reaction may proceed via a rate-determining electron transfer followed by proton transfer. The coordination of Mg<sup>2+</sup> to the carbonyl oxygen in the one-electron reduced species of GO<sup>•</sup> (GO<sup>–</sup>) may stabilize the product, resulting in the acceleration of the electron-transfer process. We also demonstrated that prophylactically administrated MLT efficiently inhibited the lipid peroxide-derived protein modification, which can be detected by a sensitive marker, <em>N</em><sup>ε</sup>-(hexanoyl)lysine adduct, in the plasma of X-irradiated mice. The relatively weak GO<sup>•</sup>-scavenging activity of MLT suggests that the ameliorative effect of MLT against in vivo lipid peroxidation does not result from the direct scavenging of lipid peroxyl radicals by MLT. Therefore, the observed superior protective efficiency of MLT against in vivo lipid peroxidation may partly support the earlier studies, which reported the synergistic antioxidative effect of the metabolites of MLT.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"3 ","pages":"Article 100003"},"PeriodicalIF":0.0,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49750806","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}
Pub Date : 2023-06-16DOI: 10.1016/j.rbc.2023.100005
Rosangela S. Santos , Márcia S.F. Franco , Felipe G. Ravagnani , Adriano B. Chaves-Filho , Sayuri Miyamoto , Mauricio S. Baptista , Mikhail S. Shchepinov , Marcos Y. Yoshinaga
Polyunsaturated fatty acids (PUFA) are particularly susceptible to free radical-induced lipid peroxidation (LPO). Specific deuteration at bis-allylic positions of PUFA (D-PUFA) has been recently proposed as a way to inhibit the LPO. Here, a high mass resolution untargeted lipidomic analysis protocol was applied to examine the changes in the lipidome of keratinocytes supplemented with bis-allylic deuterated linoleic acid (D2-LA). Incorporation of D2-LA occurs preferentially in membrane phospholipids such as phosphatidylcholine and phosphatidylethanolamine, followed by triglycerides. However, the relative contribution of D2-LA among membrane lipids is highest in cardiolipin (60%) followed by its precursor phosphatidylglycerol (50%). Cardiolipins are enriched in PUFA and exclusively located in mitochondrial membranes, thus representing major targets for lipid peroxidation. These findings indicate that D2-LA supplementation is linked to the preservation of mitochondrial function under oxidative stress. Finally, our study highlights the suitability of high mass resolution lipidomic analysis to investigate lipid metabolism at the level of individual molecular species in stable isotope tracing experiments.
{"title":"Intracellular distribution of bis-allylic deuterated linoleic acid into the lipidome of human keratinocytes","authors":"Rosangela S. Santos , Márcia S.F. Franco , Felipe G. Ravagnani , Adriano B. Chaves-Filho , Sayuri Miyamoto , Mauricio S. Baptista , Mikhail S. Shchepinov , Marcos Y. Yoshinaga","doi":"10.1016/j.rbc.2023.100005","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100005","url":null,"abstract":"<div><p>Polyunsaturated fatty acids (PUFA) are particularly susceptible to free radical-induced lipid peroxidation (LPO). Specific deuteration at bis-allylic positions of PUFA (D-PUFA) has been recently proposed as a way to inhibit the LPO. Here, a high mass resolution untargeted lipidomic analysis protocol was applied to examine the changes in the lipidome of keratinocytes supplemented with bis-allylic deuterated linoleic acid (D<sub>2</sub>-LA). Incorporation of D<sub>2</sub>-LA occurs preferentially in membrane phospholipids such as phosphatidylcholine and phosphatidylethanolamine, followed by triglycerides. However, the relative contribution of D<sub>2</sub>-LA among membrane lipids is highest in cardiolipin (60%) followed by its precursor phosphatidylglycerol (50%). Cardiolipins are enriched in PUFA and exclusively located in mitochondrial membranes, thus representing major targets for lipid peroxidation. These findings indicate that D<sub>2</sub>-LA supplementation is linked to the preservation of mitochondrial function under oxidative stress. Finally, our study highlights the suitability of high mass resolution lipidomic analysis to investigate lipid metabolism at the level of individual molecular species in stable isotope tracing experiments.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2023-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726689","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}
Pub Date : 2023-05-09DOI: 10.1016/j.rbc.2023.100004
Peter Wardman
The absorption of ionizing radiation initiates redox reactions, producing chemical species resulting from single electron loss or electron gain. Radiation chemists have developed methods to study individual redox species selectively and to monitor their reactions in real time. This has provided an enormous resource of kinetic, thermodynamic and spectroscopic information concerning the characteristics and reactions of free radicals and their redox reactions, mainly in aqueous solution. While the techniques are specialized and exploiting them is certainly more difficult than initiating redox changes by simple mixing of two chemicals or adding a reagent to a biological target, it is useful to gain an understanding of the basic mechanisms and approaches involved in exploiting radiation chemistry in the wider context of redox reactions in biochemistry, chemistry, and biology. This should enable readers both to appreciate the reliance which can be placed on the kinetic and other information resulting from such studies, as well as identify potential new applications of the technique which might be exploited in their research, by seeking partners who have access to the necessary specialized equipment or just basic irradiation facilities. This review outlines how radiation can be used to initiate selective redox reactions, mainly in water, and helps point readers to resources which should be useful in considering such reactions in a wider context.
{"title":"Initiating redox reactions by ionizing radiation: A versatile, selective and quantitative tool","authors":"Peter Wardman","doi":"10.1016/j.rbc.2023.100004","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100004","url":null,"abstract":"<div><p>The absorption of ionizing radiation initiates redox reactions, producing chemical species resulting from single electron loss or electron gain. Radiation chemists have developed methods to study individual redox species selectively and to monitor their reactions in real time. This has provided an enormous resource of kinetic, thermodynamic and spectroscopic information concerning the characteristics and reactions of free radicals and their redox reactions, mainly in aqueous solution. While the techniques are specialized and exploiting them is certainly more difficult than initiating redox changes by simple mixing of two chemicals or adding a reagent to a biological target, it is useful to gain an understanding of the basic mechanisms and approaches involved in exploiting radiation chemistry in the wider context of redox reactions in biochemistry, chemistry, and biology. This should enable readers both to appreciate the reliance which can be placed on the kinetic and other information resulting from such studies, as well as identify potential new applications of the technique which might be exploited in their research, by seeking partners who have access to the necessary specialized equipment or just basic irradiation facilities. This review outlines how radiation can be used to initiate selective redox reactions, mainly in water, and helps point readers to resources which should be useful in considering such reactions in a wider context.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2023-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726688","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}
Pub Date : 2023-04-01DOI: 10.1016/j.rbc.2022.100001
{"title":"In Memoriam: Emeritus Professor Robin L. Willson","authors":"","doi":"10.1016/j.rbc.2022.100001","DOIUrl":"https://doi.org/10.1016/j.rbc.2022.100001","url":null,"abstract":"","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49724544","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}
Pub Date : 2023-04-01DOI: 10.1016/j.rbc.2023.100002
Nicholas J. Magon, Rufus Turner, Anthony J. Kettle, Christine C. Winterbourn
Cysteine residues are the most favored targets for oxidation by hypochlorous acid and other reactive halogen species. The end-products of cysteine oxidation are usually considered to be reversibly formed disulfides and the more highly oxidized sulfinic and sulfonic acids. However, reactive halogen species are capable of generating additional products in which cysteine is cross-linked to other amino acids. Here we have treated a range of peptides with hypochlorous acid (HOCl) and hypobromous acid (HOBr), and used mass spectrometry to demonstrate sulfenamide, sulfinamide and sulfonamide formation with lysine residues, as well as –S(O)- and –S(O2)- linkages with tyrosine, tryptophan and arginine residues. The -(SO2)- products were more prevalent with HOCl than HOBr, reflecting its higher oxidizing ability. There was also considerable variation between peptides in efficiency of cross-linking compared with other modifications. The –S(O)- and –S(O2)- forms were much more resistant than the disulfide to reduction by dithiothreitol. Using calprotectin as a representative cysteine-containing protein, we show that a range of products containing each of these cross-links is formed when the protein is treated with HOCl. Two of the identified cysteine-lysine calprotectin cross-links were also detected in bronchoalveolar lavage fluid from children with cystic fibrosis. Our results imply that cross-linked species would be formed when cysteine-containing proteins are exposed to reactive halogen species, with the nature of the specific products depending on structural features around the cysteine residue. Cross-linking could have a modulatory effect on protein function or be detrimental in causing oligomerization and aggregation.
{"title":"Cross-linking between cysteine and lysine, tryptophan or tyrosine in peptides and proteins treated with hypochlorous acid and other reactive halogens","authors":"Nicholas J. Magon, Rufus Turner, Anthony J. Kettle, Christine C. Winterbourn","doi":"10.1016/j.rbc.2023.100002","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100002","url":null,"abstract":"<div><p>Cysteine residues are the most favored targets for oxidation by hypochlorous acid and other reactive halogen species. The end-products of cysteine oxidation are usually considered to be reversibly formed disulfides and the more highly oxidized sulfinic and sulfonic acids. However, reactive halogen species are capable of generating additional products in which cysteine is cross-linked to other amino acids. Here we have treated a range of peptides with hypochlorous acid (HOCl) and hypobromous acid (HOBr), and used mass spectrometry to demonstrate sulfenamide, sulfinamide and sulfonamide formation with lysine residues, as well as –S(O)- and –S(O<sub>2</sub>)- linkages with tyrosine, tryptophan and arginine residues. The -(SO<sub>2</sub>)- products were more prevalent with HOCl than HOBr, reflecting its higher oxidizing ability. There was also considerable variation between peptides in efficiency of cross-linking compared with other modifications. The –S(O)- and –S(O<sub>2</sub>)- forms were much more resistant than the disulfide to reduction by dithiothreitol. Using calprotectin as a representative cysteine-containing protein, we show that a range of products containing each of these cross-links is formed when the protein is treated with HOCl. Two of the identified cysteine-lysine calprotectin cross-links were also detected in bronchoalveolar lavage fluid from children with cystic fibrosis. Our results imply that cross-linked species would be formed when cysteine-containing proteins are exposed to reactive halogen species, with the nature of the specific products depending on structural features around the cysteine residue. Cross-linking could have a modulatory effect on protein function or be detrimental in causing oligomerization and aggregation.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49737345","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}