Pub Date : 2024-05-14DOI: 10.1016/j.rbc.2024.100027
Homero Rubbo, Andrés Trostchansky
This review explores the interaction between nitric oxide-derived reactive species and unsaturated fatty acids, leading to the formation of electrophilic nitroalkenes, named nitro-fatty acids (NO2-FA). These species serve as endogenously produced anti-inflammatory signaling mediators, demonstrating protective effects in pre-clinical animal disease models. The discussion herein focuses on the cell signaling actions of NO2-FA, drawing insights from both existing knowledge and recent in vivo data. Additionally, this review addresses the potential pharmacological utility of NO2-FA and ongoing trials, highlighting their promising prospects based on the gathered information.
{"title":"Nitro-fatty acid signaling: Therapeutic potential in inflammatory diseases","authors":"Homero Rubbo, Andrés Trostchansky","doi":"10.1016/j.rbc.2024.100027","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100027","url":null,"abstract":"<div><p>This review explores the interaction between nitric oxide-derived reactive species and unsaturated fatty acids, leading to the formation of electrophilic nitroalkenes, named nitro-fatty acids (NO<sub>2</sub>-FA). These species serve as endogenously produced anti-inflammatory signaling mediators, demonstrating protective effects in pre-clinical animal disease models. The discussion herein focuses on the cell signaling actions of NO<sub>2</sub>-FA, drawing insights from both existing knowledge and recent <em>in vivo</em> data. Additionally, this review addresses the potential pharmacological utility of NO<sub>2</sub>-FA and ongoing trials, highlighting their promising prospects based on the gathered information.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000087/pdfft?md5=851897c0771f768914061f5f1797696a&pid=1-s2.0-S2773176624000087-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950376","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}
Pub Date : 2024-05-09DOI: 10.1016/j.rbc.2024.100026
Matías N. Möller , Darío A. Vitturi
Dinitrogen trioxide (N2O3) mediates low-molecular weight and protein S- and N-nitrosation, with recent reports suggesting a role in the formation of nitrating intermediates as well as in nitrite-dependent hypoxic vasodilatation. However, the reactivity of N2O3 in biological systems results in an extremely short half-life that renders this molecule essentially undetectable by currently available technologies. As a result, evidence for in vivo N2O3 formation derives from the detection of nitrosated products as well as from in vitro kinetic determinations, isotopic labeling studies, and spectroscopic analyses. This review will discuss mechanisms of N2O3 formation, reactivity and decomposition, as well as address the role of sub-cellular localization as a key determinant of its actions. Finally, evidence will be discussed supporting different roles for N2O3 as a biologically relevant signaling molecule.
{"title":"The chemical biology of dinitrogen trioxide","authors":"Matías N. Möller , Darío A. Vitturi","doi":"10.1016/j.rbc.2024.100026","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100026","url":null,"abstract":"<div><p>Dinitrogen trioxide (N<sub>2</sub>O<sub>3</sub>) mediates low-molecular weight and protein S- and N-nitrosation, with recent reports suggesting a role in the formation of nitrating intermediates as well as in nitrite-dependent hypoxic vasodilatation. However, the reactivity of N<sub>2</sub>O<sub>3</sub> in biological systems results in an extremely short half-life that renders this molecule essentially undetectable by currently available technologies. As a result, evidence for <em>in vivo</em> N<sub>2</sub>O<sub>3</sub> formation derives from the detection of nitrosated products as well as from <em>in vitro</em> kinetic determinations, isotopic labeling studies, and spectroscopic analyses. This review will discuss mechanisms of N<sub>2</sub>O<sub>3</sub> formation, reactivity and decomposition, as well as address the role of sub-cellular localization as a key determinant of its actions. Finally, evidence will be discussed supporting different roles for N<sub>2</sub>O<sub>3</sub> as a biologically relevant signaling molecule.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100026"},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000075/pdfft?md5=a6dcbb5b09dfa3f7a85e72ede30c0872&pid=1-s2.0-S2773176624000075-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140950371","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}
Pub Date : 2024-04-26DOI: 10.1016/j.rbc.2024.100025
Christopher J. Barry , Ché S. Pillay , Johann M. Rohwer
The peroxiredoxins are an important antioxidant protein family and their ability to neutralise oxidants is regularly investigated using horse radish peroxidase in a competition assay system. In this method, the rate constant of a peroxiredoxin is calculated from the fractional inhibition of horse radish peroxidase activity caused by competition with the peroxiredoxin for an oxidant substrate. We developed a model capable of simulating this assay and, using this model, demonstrate that the fractional inhibition calculation significantly and systematically mis-estimates the rate constant under fairly common conditions. We go on to develop a method for fitting simulated assay time-courses to experimental data directly, which significantly outperforms the fractional inhibition method yielding more accurate results. Based on our findings, we recommend using the direct fitting approach to determine peroxidase rate constants from horseradish peroxidase experiments.
{"title":"Direct fitting improves the accuracy of the horse radish peroxidase competition assay for peroxidase activity","authors":"Christopher J. Barry , Ché S. Pillay , Johann M. Rohwer","doi":"10.1016/j.rbc.2024.100025","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100025","url":null,"abstract":"<div><p>The peroxiredoxins are an important antioxidant protein family and their ability to neutralise oxidants is regularly investigated using horse radish peroxidase in a competition assay system. In this method, the rate constant of a peroxiredoxin is calculated from the fractional inhibition of horse radish peroxidase activity caused by competition with the peroxiredoxin for an oxidant substrate. We developed a model capable of simulating this assay and, using this model, demonstrate that the fractional inhibition calculation significantly and systematically mis-estimates the rate constant under fairly common conditions. We go on to develop a method for fitting simulated assay time-courses to experimental data directly, which significantly outperforms the fractional inhibition method yielding more accurate results. Based on our findings, we recommend using the direct fitting approach to determine peroxidase rate constants from horseradish peroxidase experiments.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000063/pdfft?md5=d1ae63fed576a6bb22d227fdefdd47ca&pid=1-s2.0-S2773176624000063-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823817","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}
Pub Date : 2024-04-22DOI: 10.1016/j.rbc.2024.100024
Sebastian A. Suarez
This review focuses on HNO, a molecule of immense chemical and biological importance that has intrigued scientists for decades. Despite its elusive and transient nature, HNO may play an important role in various physiological processes, particularly in cardiovascular regulation. This review thoroughly examines the formation, chemical properties, and biological significance of HNO and highlights ongoing research efforts to unravel its mysteries. Challenges in studying HNO arise from its high reactivity, short half-life, and complex interactions with other nitrogen oxides, particularly nitric oxide. Detection and quantification of HNO in biological systems pose difficulties, prompting the development of advanced techniques. Active research into endogenous HNO formation is revealing intricate pathways within biological systems, the elucidation of which is crucial for exploiting its therapeutic potential. The multifaceted role of HNO in cardiovascular regulation, influencing vasorelaxation, blood pressure reduction, and enhanced cardiac contractility, underscores its profound impact on the circulatory system. Ongoing research holds promise for treating conditions such as hypertension and heart failure. As clinical applications expand, HNO research may unlock treatments for cardiovascular disease, inflammatory disorders, and cancer. The recent discovery of endogenous HNO production in plants adds a new dimension. While numerous clues have emerged, the scientific saga underscores that mysteries persist, evolve, and beckon to perpetual exploration in the realm of science.
{"title":"Decoding the enigmatic last gasotransmitter. The intriguing journey of HNO: From hidden origins to clues on reactivity and detection","authors":"Sebastian A. Suarez","doi":"10.1016/j.rbc.2024.100024","DOIUrl":"10.1016/j.rbc.2024.100024","url":null,"abstract":"<div><p>This review focuses on HNO, a molecule of immense chemical and biological importance that has intrigued scientists for decades. Despite its elusive and transient nature, HNO may play an important role in various physiological processes, particularly in cardiovascular regulation. This review thoroughly examines the formation, chemical properties, and biological significance of HNO and highlights ongoing research efforts to unravel its mysteries. Challenges in studying HNO arise from its high reactivity, short half-life, and complex interactions with other nitrogen oxides, particularly nitric oxide. Detection and quantification of HNO in biological systems pose difficulties, prompting the development of advanced techniques. Active research into endogenous HNO formation is revealing intricate pathways within biological systems, the elucidation of which is crucial for exploiting its therapeutic potential. The multifaceted role of HNO in cardiovascular regulation, influencing vasorelaxation, blood pressure reduction, and enhanced cardiac contractility, underscores its profound impact on the circulatory system. Ongoing research holds promise for treating conditions such as hypertension and heart failure. As clinical applications expand, HNO research may unlock treatments for cardiovascular disease, inflammatory disorders, and cancer. The recent discovery of endogenous HNO production in plants adds a new dimension. While numerous clues have emerged, the scientific saga underscores that mysteries persist, evolve, and beckon to perpetual exploration in the realm of science.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000051/pdfft?md5=072377c74312656eca6afa81588537c0&pid=1-s2.0-S2773176624000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763633","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}
Pub Date : 2024-04-04DOI: 10.1016/j.rbc.2024.100022
Inga Sileikaite-Morvaközi , Ksenia Morozova , Nadezda A. Brazhe , Olga Sosnovtseva , Claus Desler , Thomas Mandrup-Poulsen , Michael J. Davies , Clare L. Hawkins
The production of reactive oxygen species and oxidative stress promote β-cell dysfunction and impair insulin secretion, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). The nucleobase guanine is highly sensitive to oxidation, which results in the formation of 8-oxoguanosine (8oxoG) and 8-oxodeoxyguanosine (8oxodG). The urinary excretion of 8oxoG is associated with the risk of mortality in people with T2DM, including from diabetic complications such as cardiovascular disease. However, the cellular mechanisms responsible for this association are poorly defined. Therefore, in this study, we examined the effect of 8oxoG, 8oxodG and other oxidized guanosine derivatives, on the INS-1E β-cell line. Exposure of INS-1E cells to 8oxoG and 8oxodG decreased metabolic activity and promoted cell death by apoptosis. The change in cell viability was similar to that induced by treatment of INS-1E cells with the inflammatory cytokines interleukin 1β (Il-1β) and tumour necrosis factor α (TNFα). Changes in mitochondrial membrane permeability and superoxide radical formation were also observed with 8oxoG, but there was no significant change in the oxidation state of mitochondrial cytochromes or hydrogen peroxide levels in the INS-1E cells. Interestingly, exposure to 8oxoG and 8-oxodG also increased the mRNA expression of stress response genes, including NADPH dehydrogenase quinone 1 (NQO1), and thioredoxin-interacting protein (TXNIP). Together, these results support a potential role of oxidized guanosine derivatives in the induction of β-cell dysfunction, which could be relevant to the pathogenesis of T2DM.
{"title":"Oxidized guanosines induce mitochondrial dysfunction and loss of viability in β-cells","authors":"Inga Sileikaite-Morvaközi , Ksenia Morozova , Nadezda A. Brazhe , Olga Sosnovtseva , Claus Desler , Thomas Mandrup-Poulsen , Michael J. Davies , Clare L. Hawkins","doi":"10.1016/j.rbc.2024.100022","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100022","url":null,"abstract":"<div><p>The production of reactive oxygen species and oxidative stress promote β-cell dysfunction and impair insulin secretion, thereby contributing to the pathogenesis of type 2 diabetes mellitus (T2DM). The nucleobase guanine is highly sensitive to oxidation, which results in the formation of 8-oxoguanosine (8oxoG) and 8-oxodeoxyguanosine (8oxodG). The urinary excretion of 8oxoG is associated with the risk of mortality in people with T2DM, including from diabetic complications such as cardiovascular disease. However, the cellular mechanisms responsible for this association are poorly defined. Therefore, in this study, we examined the effect of 8oxoG, 8oxodG and other oxidized guanosine derivatives, on the INS-1E β-cell line. Exposure of INS-1E cells to 8oxoG and 8oxodG decreased metabolic activity and promoted cell death by apoptosis. The change in cell viability was similar to that induced by treatment of INS-1E cells with the inflammatory cytokines interleukin 1β (Il-1β) and tumour necrosis factor α (TNFα). Changes in mitochondrial membrane permeability and superoxide radical formation were also observed with 8oxoG, but there was no significant change in the oxidation state of mitochondrial cytochromes or hydrogen peroxide levels in the INS-1E cells. Interestingly, exposure to 8oxoG and 8-oxodG also increased the mRNA expression of stress response genes, including NADPH dehydrogenase quinone 1 (NQO1), and thioredoxin-interacting protein (TXNIP). Together, these results support a potential role of oxidized guanosine derivatives in the induction of β-cell dysfunction, which could be relevant to the pathogenesis of T2DM.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100022"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000038/pdfft?md5=bdee5885ca4a34f13fa105f9aac9f767&pid=1-s2.0-S2773176624000038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140539119","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}
Pub Date : 2024-04-04DOI: 10.1016/j.rbc.2024.100021
Bessie B. Ríos-González , Andrea Domán , Tamás Ditrói , Dorottya Garai , Leishka D. Crespo , Gary J. Gerfen , Paul G. Furtmüller , Péter Nagy , Juan López-Garriga
The biological chemistry of hydrogen sulfide (H2S) with physiologically important heme proteins is in the focus of redox biology research. In this study, we investigated the interactions of lactoperoxidase (LPO) with H2S in the presence and absence of molecular dioxygen (O2) or hydrogen peroxide (H2O2). Under anaerobic conditions, native LPO forms no heme-H2S complex upon sulfide exposure. However, under aerobic conditions or in the presence of H2O2 the formation of both ferrous and ferric sulfheme (sulfLPO) derivatives was observed based on the appearances of their characteristic optical absorptions at 638 nm and 727 nm, respectively. Interestingly, we demonstrate that LPO can catalytically oxidize H2S by H2O2 via intermediate formation of relatively short-lived ferrous and ferric sulfLPO derivatives. Pilot product analyses suggested that the turnover process generates oxidized sulfide species, which include sulfate (SO42−) and inorganic polysulfides (HSx−; x = 2–5). These results indicated that H2S can serve as a non-classical LPO substrate by inducing a reversible sulfheme-like modification of the heme porphyrin ring during turnover. Furthermore, electron paramagnetic resonance data suggest that H2S can act as a scavenger of H2O2 in the presence of LPO without detectable formation of any carbon-centered protein radical species, suggesting that H2S might be capable of protecting the enzyme from radical-mediated damage. We propose possible mechanisms, which explain our results as well as contrasting observations with other heme proteins, where either no sulfheme formation was observed or the generation of sulfheme derivatives provided a dead end for enzyme functions.
{"title":"Lactoperoxidase catalytically oxidize hydrogen sulfide via intermediate formation of sulfheme derivatives","authors":"Bessie B. Ríos-González , Andrea Domán , Tamás Ditrói , Dorottya Garai , Leishka D. Crespo , Gary J. Gerfen , Paul G. Furtmüller , Péter Nagy , Juan López-Garriga","doi":"10.1016/j.rbc.2024.100021","DOIUrl":"https://doi.org/10.1016/j.rbc.2024.100021","url":null,"abstract":"<div><p>The biological chemistry of hydrogen sulfide (H<sub>2</sub>S) with physiologically important heme proteins is in the focus of redox biology research. In this study, we investigated the interactions of lactoperoxidase (LPO) with H<sub>2</sub>S in the presence and absence of molecular dioxygen (O<sub>2</sub>) or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>). Under anaerobic conditions, native LPO forms no heme-H<sub>2</sub>S complex upon sulfide exposure. However, under aerobic conditions or in the presence of H<sub>2</sub>O<sub>2</sub> the formation of both ferrous and ferric sulfheme (sulfLPO) derivatives was observed based on the appearances of their characteristic optical absorptions at 638 nm and 727 nm, respectively. Interestingly, we demonstrate that LPO can catalytically oxidize H<sub>2</sub>S by H<sub>2</sub>O<sub>2</sub> via intermediate formation of relatively short-lived ferrous and ferric sulfLPO derivatives. Pilot product analyses suggested that the turnover process generates oxidized sulfide species, which include sulfate (SO<sub>4</sub><sup>2−</sup>) and inorganic polysulfides (HS<sub>x</sub><sup>−</sup>; x = 2–5). These results indicated that H<sub>2</sub>S can serve as a non-classical LPO substrate by inducing a reversible sulfheme-like modification of the heme porphyrin ring during turnover. Furthermore, electron paramagnetic resonance data suggest that H<sub>2</sub>S can act as a scavenger of H<sub>2</sub>O<sub>2</sub> in the presence of LPO without detectable formation of any carbon-centered protein radical species, suggesting that H<sub>2</sub>S might be capable of protecting the enzyme from radical-mediated damage. We propose possible mechanisms, which explain our results as well as contrasting observations with other heme proteins, where either no sulfheme formation was observed or the generation of sulfheme derivatives provided a dead end for enzyme functions.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"8 ","pages":"Article 100021"},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000026/pdfft?md5=c98d3efbf75f1105ec44b5dd1c758983&pid=1-s2.0-S2773176624000026-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140549042","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}
Pub Date : 2024-03-22DOI: 10.1016/j.rbc.2024.100020
Sara Goldstein , Amram Samuni
Nitrogen dioxide (•NO2) is a radical gas that forms part of air pollution and is produced chemically, photochemically and by ionizing radiation in aqueous and non-aqueous solutions as well as by various endogenous pathways in biological systems. This review describes the: (i) sources of •NO2; (ii) kinetics and mechanism of •NO2 reactions; (iii) •NO2 as a key player in cellular oxidative and nitrosative stress leading to pathological conditions, and (iv) use of diverse antioxidants to reduce •NO2 toxic effects.
{"title":"Chemistry of nitrogen dioxide and its biological implicatios","authors":"Sara Goldstein , Amram Samuni","doi":"10.1016/j.rbc.2024.100020","DOIUrl":"10.1016/j.rbc.2024.100020","url":null,"abstract":"<div><p>Nitrogen dioxide (<sup>•</sup>NO<sub>2</sub>) is a radical gas that forms part of air pollution and is produced chemically, photochemically and by ionizing radiation in aqueous and non-aqueous solutions as well as by various endogenous pathways in biological systems. This review describes the: (<em>i</em>) sources of <sup>•</sup>NO<sub>2</sub>; (<em>ii</em>) kinetics and mechanism of <sup>•</sup>NO<sub>2</sub> reactions; (<em>iii</em>) <sup>•</sup>NO<sub>2</sub> as a key player in cellular oxidative and nitrosative stress leading to pathological conditions, and <em>(iv)</em> use of diverse antioxidants to reduce <sup>•</sup>NO<sub>2</sub> toxic effects.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176624000014/pdfft?md5=1281d8224d83c88cf2e2284ffe34567c&pid=1-s2.0-S2773176624000014-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140268890","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}
Pub Date : 2023-12-12DOI: 10.1016/j.rbc.2023.100019
Diana A. Averill-Bates, André Tanel
Interest in the molecular actions of acrolein has increased in light of growing knowledge that implicates this reactive aldehyde in a wide range of pathophysiologies including neurodegenerative diseases, various lung disorders including chronic obstructive pulmonary disease, atherosclerosis, and certain cancers. This is rendered complex because acrolein exists in mixtures of environmental pollutants. Reactive α,β-unsaturated aldehydes like acrolein are major components of common environmental pollutants like cigarettes, automobile exhaust, and smoke from wood, coal, forest and house fires. It is a natural constituent of several foods and is generated in the human body during inflammation or oxidation of unsaturated lipids. Acrolein is also a toxic metabolic product of the widely used anticancer drug cyclophosphamide and is generated from the enzymatic oxidation of polyamines. It is a toxic by-product of lipid peroxidation and has been implicated as a mediator of oxidative damage in cells and tissues. The purpose of this review is to assess the literature about the activation of cell signalling pathways and transcription factors, and cell survival and cell death pathways by acrolein. Several reports show that anti-apoptosis processes dominate at lower dose exposures to acrolein, whereas pro-apoptotic processes and necrosis dominate at higher dose exposures. There has been improved understanding about the deleterious molecular and cellular mechanisms that are triggered in cells in response to acrolein injury. However, more progress is required to define the contributions of acrolein to human diseases and to design efficient therapeutic strategies based on the biochemical modulation of acrolein activity.
{"title":"Activation of cellular signalling pathways and apoptosis by the aldehyde acrolein – A major environmental hazard","authors":"Diana A. Averill-Bates, André Tanel","doi":"10.1016/j.rbc.2023.100019","DOIUrl":"10.1016/j.rbc.2023.100019","url":null,"abstract":"<div><p>Interest in the molecular actions of acrolein has increased in light of growing knowledge that implicates this reactive aldehyde in a wide range of pathophysiologies including neurodegenerative diseases, various lung disorders including chronic obstructive pulmonary disease, atherosclerosis, and certain cancers. This is rendered complex because acrolein exists in mixtures of environmental pollutants. Reactive α,β-unsaturated aldehydes like acrolein are major components of common environmental pollutants like cigarettes, automobile exhaust, and smoke from wood, coal, forest and house fires. It is a natural constituent of several foods and is generated in the human body during inflammation or oxidation of unsaturated lipids. Acrolein is also a toxic metabolic product of the widely used anticancer drug cyclophosphamide and is generated from the enzymatic oxidation of polyamines. It is a toxic by-product of lipid peroxidation and has been implicated as a mediator of oxidative damage in cells and tissues. The purpose of this review is to assess the literature about the activation of cell signalling pathways and transcription factors, and cell survival and cell death pathways by acrolein. Several reports show that anti-apoptosis processes dominate at lower dose exposures to acrolein, whereas pro-apoptotic processes and necrosis dominate at higher dose exposures. There has been improved understanding about the deleterious molecular and cellular mechanisms that are triggered in cells in response to acrolein injury. However, more progress is required to define the contributions of acrolein to human diseases and to design efficient therapeutic strategies based on the biochemical modulation of acrolein activity.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100019"},"PeriodicalIF":0.0,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176623000184/pdfft?md5=9c33fed1db3a45958274b57c9b23009a&pid=1-s2.0-S2773176623000184-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138988898","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}
Pub Date : 2023-11-28DOI: 10.1016/j.rbc.2023.100018
Xing Zhang , Shuqi Xu , Christine Y. Chuang , Brian J. Day , Clare L. Hawkins , Michael J. Davies
The leukocyte-derived enzyme myeloperoxidase (MPO) is a key component of the innate immune response and mediates the killing of pathogens via the generation of the powerful oxidant hypochlorous acid (HOCl). Unintended or excessive formation of this species can however result in damage to host tissues, and this is linked with multiple pathologies associated with acute or chronic inflammation. The active (Compound I) form of MPO is promiscuous and can oxidize multiple alternative anions, in addition to the Cl− used to generate HOCl. These alternative substrates may therefore modulate MPO-mediated HOCl damage. In the current study we examined the hypothesis that selenocyanate (SeCN−), the selenium analogue of thiocyanate (SCN−, a well-established competitive MPO substrate) would inhibit HOCl-mediated damage to human plasma fibronectin (hpFN) or the extracellular matrix laid down by human coronary artery smooth muscle cells. SeCN− modulated HOCl and MPO-mediated damage, in a dose-dependent manner. These data are consistent with SeCN− acting as both a competitive substrate for Compound I of MPO (with IC50 ∼23 μM), and as a direct scavenger of HOCl. Inhibition of protein damage by SeCN− was also detected in the presence of the physiological anions Br−, I− and SCN− at the concentrations typically present in human plasma, consistent with a high affinity of SeCN− for MPO Compound I. In addition, the protective effects of SeCN− and SCN−, as competitive MPO substrates, were additive. Together these data indicate that modest concentrations of SeCN− can, like its sulfur analogue SCN−, act as an effective modulator of inflammation-induced damage.
{"title":"Selenocyanate (SeCN−) acts as an efficient competitive substrate for myeloperoxidase and decreases biological damage induced by hypochlorous acid","authors":"Xing Zhang , Shuqi Xu , Christine Y. Chuang , Brian J. Day , Clare L. Hawkins , Michael J. Davies","doi":"10.1016/j.rbc.2023.100018","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100018","url":null,"abstract":"<div><p>The leukocyte-derived enzyme myeloperoxidase (MPO) is a key component of the innate immune response and mediates the killing of pathogens via the generation of the powerful oxidant hypochlorous acid (HOCl). Unintended or excessive formation of this species can however result in damage to host tissues, and this is linked with multiple pathologies associated with acute or chronic inflammation. The active (Compound I) form of MPO is promiscuous and can oxidize multiple alternative anions, in addition to the Cl<sup>−</sup> used to generate HOCl. These alternative substrates may therefore modulate MPO-mediated HOCl damage. In the current study we examined the hypothesis that selenocyanate (SeCN<sup>−</sup>), the selenium analogue of thiocyanate (SCN<sup>−</sup>, a well-established competitive MPO substrate) would inhibit HOCl-mediated damage to human plasma fibronectin (hpFN) or the extracellular matrix laid down by human coronary artery smooth muscle cells. SeCN<sup>−</sup> modulated HOCl and MPO-mediated damage, in a dose-dependent manner. These data are consistent with SeCN<sup>−</sup> acting as both a competitive substrate for Compound I of MPO (with IC<sub>50</sub> ∼23 μM), and as a direct scavenger of HOCl. Inhibition of protein damage by SeCN<sup>−</sup> was also detected in the presence of the physiological anions Br<sup>−</sup>, I<sup>−</sup> and SCN<sup>−</sup> at the concentrations typically present in human plasma, consistent with a high affinity of SeCN<sup>−</sup> for MPO Compound I. In addition, the protective effects of SeCN<sup>−</sup> and SCN<sup>−</sup>, as competitive MPO substrates, were additive. Together these data indicate that modest concentrations of SeCN<sup>−</sup> can, like its sulfur analogue SCN<sup>−</sup>, act as an effective modulator of inflammation-induced damage.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"7 ","pages":"Article 100018"},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773176623000172/pdfft?md5=4ce4a3466ab4e55a3ca75be7e8b6ea2f&pid=1-s2.0-S2773176623000172-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138549547","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}
Pub Date : 2023-09-27DOI: 10.1016/j.rbc.2023.100015
Dorian M. Cheff , Helena Skröder , Evana Akhtar , Qing Cheng , Matthew D. Hall , Rubhana Raqib , Maria Kippler , Marie Vahter , Elias S.J. Arnér
Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (rs = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and C-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (rs = −0.395, p < 0.0001), and CRP levels also negatively impacted GPX1 activity (rs = −0.443, p < 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (rs = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.
{"title":"Arsenic exposure and increased C-reactive protein are independently associated with lower erythrocyte glutathione peroxidase activity in Bangladeshi children","authors":"Dorian M. Cheff , Helena Skröder , Evana Akhtar , Qing Cheng , Matthew D. Hall , Rubhana Raqib , Maria Kippler , Marie Vahter , Elias S.J. Arnér","doi":"10.1016/j.rbc.2023.100015","DOIUrl":"https://doi.org/10.1016/j.rbc.2023.100015","url":null,"abstract":"<div><p>Toxic metal contaminants present in food and water have widespread effects on health and disease. Chalcophiles, such as arsenic, cadmium, and mercury, show a high affinity to selenium and exposure to these metals could have a modulating effect on enzymes dependent on selenocysteine in their active sites. The aim of this study was to assess the influence of these metals on the activity of the selenoprotein glutathione peroxidase 1 (GPX1) in erythrocytes of 100 children residing in rural Bangladesh, where drinking water often contains arsenic. GPX1 expression, as measured using high-throughput immunoblotting, showed little correlation with GPX activity (<em>r</em><sub><em>s</em></sub> = 0.02, p = 0.87) in blood samples. Toxic metals and selenium measured in erythrocytes using inductively coupled plasma mass spectrometry (ICP-MS) and <em>C</em>-reactive protein (CRP) measured in plasma, were all considered as effectors of this divergence in GPX enzymatic activity. Arsenic concentrations in erythrocytes were most influential for GPX1 activity (<em>r</em><sub><em>s</em></sub> = −0.395, p < 0.0001), and CRP levels also negatively impacted GPX1 activity (<em>r</em><sub><em>s</em></sub> = −0.443, p < 0.0001). These effects appear independent of each other as arsenic concentrations and CRP showed no correlation (<em>r</em><sub><em>s</em></sub> = 0.124, p = 0.2204). Erythrocyte selenium, cadmium, and mercury did not show any correlation with GPX1 activity, nor with CRP or arsenic. Our findings suggest that childhood exposure to inorganic arsenic, as well as inflammation triggering the release of CRP, may negatively affect GPX1 activity in erythrocytes.</p></div>","PeriodicalId":101065,"journal":{"name":"Redox Biochemistry and Chemistry","volume":"5 ","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49726672","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}