Editorial

3 pages, 186 KiB

Open AccessEditorial

Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification

by Giancarlo Aldini and Alessandra A. Altomare

Antioxidants 2021, 10(5), 690; https://doi.org/10.3390/antiox10050690 - 28 Apr 2021

Cited by 2 | Viewed by 1513

Abstract

The Special issue is composed of 13 contributions: 9 research papers and 4 reviews [...] Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

Research

Jump to: Editorial, Review

14 pages, 2550 KiB

Open AccessEditor’s ChoiceArticle

Allysine and α-Aminoadipic Acid as Markers of the Glyco-Oxidative Damage to Human Serum Albumin under Pathological Glucose Concentrations

by Carolina Luna, Alexis Arjona, Carmen Dueñas and Mario Estevez

Antioxidants 2021, 10(3), 474; https://doi.org/10.3390/antiox10030474 - 17 Mar 2021

Cited by 13 | Viewed by 2675

Abstract

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such [...] Read more.

Understanding the molecular basis of the disease is of the utmost scientific interest as it contributes to the development of targeted strategies of prevention, diagnosis, and therapy. Protein carbonylation is a typical feature of glyco-oxidative stress and takes place in health disorders such as diabetes. Allysine as well as its oxidation product, the α-amino adipic acid (α-AA) have been found to be markers of diabetes risk whereas little is known about the chemistry involved in its formation under hyperglycemic conditions. To provide insight into this issue, human serum albumin was incubated in the presence of FeCl3 (25 μM) and increasing glucose concentrations for 32 h at 37 °C. These concentrations were selected to simulate (i) physiological fasting plasma concentration (4 mM), (ii) pathological pre-diabetes fasting plasma concentration (8 mM), and pathological diabetes fasting plasma concentration (12 mM) of glucose. While both allysine and α-AA were found to increase with increasing glucose concentrations, the carboxylic acid was only detected at pathological glucose concentrations and appeared to be a more reliable indicator of glyco-oxidative stress. The underlying chemical mechanisms of lysine glycation as well as of the depletion of tryptophan and formation of fluorescent and colored advanced glycation products are discussed. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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21 pages, 4352 KiB

Open AccessEditor’s ChoiceArticle

A Workflow towards the Reproducible Identification and Quantitation of Protein Carbonylation Sites in Human Plasma

by Juan Camilo Rojas Echeverri, Sanja Milkovska-Stamenova and Ralf Hoffmann

Antioxidants 2021, 10(3), 369; https://doi.org/10.3390/antiox10030369 - 01 Mar 2021

Cited by 12 | Viewed by 2891

Abstract

Protein carbonylation, a marker of excessive oxidative stress, has been studied in the context of multiple human diseases related to oxidative stress. The variety of post-translational carbonyl modifications (carbonyl PTMs) and their low concentrations in plasma challenge their reproducible identification and quantitation. However, [...] Read more.

Protein carbonylation, a marker of excessive oxidative stress, has been studied in the context of multiple human diseases related to oxidative stress. The variety of post-translational carbonyl modifications (carbonyl PTMs) and their low concentrations in plasma challenge their reproducible identification and quantitation. However, carbonyl-specific biotinylated derivatization tags (e.g., aldehyde reactive probe, ARP) allow for targeting carbonyl PTMs by enriching proteins and peptides carrying these modifications. In this study, an oxidized human serum albumin protein model (OxHSA) and plasma from a healthy donor were derivatized with ARP, digested with trypsin, and enriched using biotin-avidin affinity chromatography prior to nano reversed-phase chromatography coupled online to electrospray ionization tandem mass spectrometry with travelling wave ion mobility spectrometry (nRPC-ESI-MS/MS-TWIMS). The presented workflow addresses several analytical challenges by using ARP-specific fragment ions to reliably identify ARP peptides. Furthermore, the reproducible recovery and relative quantitation of ARP peptides were validated. Human serum albumin (HSA) in plasma was heavily modified by a variety of direct amino acid oxidation products and adducts from reactive carbonyl species (RCS), with most RCS modifications being detected in six hotspots, i.e., Lys10, Lys190, Lys199, Lys281, Lys432, and Lys525 of mature HSA. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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14 pages, 3036 KiB

Open AccessArticle

4-Hydroxynonenal Contributes to Fibroblast Senescence in Skin Photoaging Evoked by UV-A Radiation

by Audrey Swiader, Caroline Camaré, Paul Guerby, Robert Salvayre and Anne Negre-Salvayre

Antioxidants 2021, 10(3), 365; https://doi.org/10.3390/antiox10030365 - 28 Feb 2021

Cited by 14 | Viewed by 3523

Abstract

Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and [...] Read more.

Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and lipid peroxidation. We previously reported that 4-hydroxynonenal (HNE), a lipid peroxidation-derived aldehyde, forms adducts on elastin in the skins of UV-A irradiated hairless mice, possibly contributing to actinic elastosis. In the present study, we investigated whether and how HNE promotes fibroblast senescence in skin photoaging. Dermal fibroblasts of skins from UV-A-exposed hairless mice exhibited an increased number of γH2AX foci characteristic of cell senescence, together with an accumulation of HNE adducts partly colocalizing with the cytoskeletal protein vimentin. Murine fibroblasts exposed to UV-A radiation (two cycles of 15 J/cm²), or HNE (30 µM, 4 h), exhibited senescence patterns characterized by an increased γH2AX foci expression, an accumulation of acetylated proteins, and a decreased expression of the sirtuin SIRT1. HNE adducts were detected on vimentin in cultured fibroblasts irradiated by UV-A or incubated with HNE. The HNE scavenger carnosine prevented both vimentin modification and fibroblast senescence evoked by HNE in vitro and in the skins of UV-A-exposed mice. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in fibroblast senescence, and confirm the protective effect of carnosine in skin photoaging. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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21 pages, 1863 KiB

Open AccessEditor’s ChoiceArticle

In-Depth AGE and ALE Profiling of Human Albumin in Heart Failure: Ex Vivo Studies

by Alessandra Altomare, Giovanna Baron, Marta Balbinot, Alma Martínez Fernández, Alessandro Pedretti, Beatrice Zoanni, Maura Brioschi, Piergiuseppe Agostoni, Marina Carini, Cristina Banfi and Giancarlo Aldini

Antioxidants 2021, 10(3), 358; https://doi.org/10.3390/antiox10030358 - 27 Feb 2021

Cited by 5 | Viewed by 3135

Abstract

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma [...] Read more.

Advanced glycation end-products (AGEs) and advanced lipoxidation end-products (ALEs), particularly carboxymethyl-lysine (CML), have been largely proposed as factors involved in the establishment and progression of heart failure (HF). Despite this evidence, the current literature lacks the comprehensive identification and characterization of the plasma AGEs/ALEs involved in HF (untargeted approach). This work provides the first ex vivo high-resolution mass spectrometry (HR-MS) profiling of AGEs/ALEs occurring in human serum albumin (HSA), the most abundant protein in plasma, characterized by several nucleophilic sites and thus representing the main protein substrate for AGE/ALE formation. A set of AGE/ALE adducts in pooled HF-HSA samples was defined, and a semi-quantitative analysis was carried out in order to finally select those presenting in increased amounts in the HF samples with respect to the control condition. These adducts were statistically confirmed by monitoring their content in individual HF samples by applying a targeted approach. Selected AGEs/ALEs proved to be mostly CML derivatives on Lys residues (i.e., CML-Lys12, CML-Lys378, CML-Lys402), and one deoxy-fructosyl derivative on the Lys 389 (DFK-Lys 389). The nature of CML adducts was finally confirmed using immunological methods and in vitro production of such adducts further confirmed by mass spectrometry. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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10 pages, 920 KiB

Open AccessCommunication

Heme-Iron-Induced Production of 4-Hydroxynonenal in Intestinal Lumen May Have Extra-Intestinal Consequences through Protein-Adduct Formation

by Julia Keller, Sylvie Chevolleau, Maria-Helena Noguer-Meireles, Estelle Pujos-Guillot, Mylène Delosière, Céline Chantelauze, Charlotte Joly, Florence Blas-y-Estrada, Isabelle Jouanin, Denys Durand, Fabrice Pierre, Laurent Debrauwer, Vassilia Theodorou and Françoise Guéraud

Antioxidants 2020, 9(12), 1293; https://doi.org/10.3390/antiox9121293 - 17 Dec 2020

Cited by 9 | Viewed by 2436

Abstract

Some epidemiological studies show that heme iron consumption, in red meat, is associated to the development of several chronic diseases, including cancers and cardio-metabolic diseases. As heme iron intestinal absorption is finely regulated, we hypothesized that heme iron may act indirectly, through the [...] Read more.

Some epidemiological studies show that heme iron consumption, in red meat, is associated to the development of several chronic diseases, including cancers and cardio-metabolic diseases. As heme iron intestinal absorption is finely regulated, we hypothesized that heme iron may act indirectly, through the peroxidation of dietary lipids, in food or in the intestinal lumen during digestion. This heme-iron-induced lipid peroxidation provokes the generation of toxic lipid oxidation products that could be absorbed, such as 4-hydroxynonenal (HNE). In a first experiment, heme iron given to rats by oral gavage together with the linoleic-acid-rich safflower oil induced the formation of HNE in the intestinal lumen. The HNE major urinary metabolite was elevated in the urine of the treated rats, indicating that this compound has been absorbed. In a second experiment, we showed that stable isotope-labeled HNE given orally to rats was able to reach non-intestinal tissues as a bioactive form and to make protein-adducts in heart, liver and skeletal muscle tissues. The presence of HNE-protein adducts in those tissues suggests a putative biological role of diet-originating HNE in extra-intestinal organs. This finding could have major consequences on the onset/development of chronic diseases associated with red meat over-consumption, and more largely to peroxidation-prone food consumption. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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13 pages, 2722 KiB

Open AccessEditor’s ChoiceArticle

Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

by Amy K. Hauck, Tong Zhou, Ambuj Upadhyay, Yuxiang Sun, Michael B. O’Connor, Yue Chen and David A. Bernlohr

Antioxidants 2020, 9(12), 1210; https://doi.org/10.3390/antiox9121210 - 01 Dec 2020

Cited by 13 | Viewed by 2628

Abstract

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and [...] Read more.

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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14 pages, 2204 KiB

Open AccessArticle

Downregulation of the Glo1 Gene Is Associated with Reduced Adiposity and Ectopic Fat Accumulation in Spontaneously Hypertensive Rats

by Jan Šilhavý, Hana Malínská, Martina Hüttl, Irena Marková, Olena Oliyarnyk, Petr Mlejnek, Miroslava Šimáková, František Liška, Ludmila Kazdová, Radka Moravcová, Jiří Novotný and Michal Pravenec

Antioxidants 2020, 9(12), 1179; https://doi.org/10.3390/antiox9121179 - 26 Nov 2020

Cited by 5 | Viewed by 2379

Abstract

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the [...] Read more.

Methylglyoxal (MG), a potent precursor of advanced glycation end-products (AGE), is increased in metabolic disorders such as diabetes and obesity. MG and other dicarbonyl metabolites are detoxified by the glyoxalase system in which glyoxalase 1, coded by the Glo1 gene, serves as the rate-limiting enzyme. In this study, we analyzed the effects of Glo1 downregulation on glucose and lipid metabolism parameters in spontaneously hypertensive rats (SHR) by targeting the Glo1 gene (SHR-Glo1^+/− heterozygotes). Compared to SHR wild-type animals, SHR-Glo1^+/− rats showed significantly reduced Glo1 expression and lower GLO1 activity in tissues associated with increased MG levels. In contrast to SHR controls, SHR-Glo1^+/− rats exhibited lower relative weight of epididymal fat, reduced ectopic fat accumulation in the liver and heart, and decreased serum triglycerides. In addition, compared to controls, SHR-Glo1^+/− rats showed reduced serum insulin and increased basal and insulin stimulated incorporation of glucose into white adipose tissue lipids (lipogenesis). Reduced ectopic fat accumulation in the heart was associated with significantly increased pAMPK/AMPK ratio and GLUT4 activity. These results provide evidence that Glo1 downregulation in SHR is associated with reduced adiposity and ectopic fat accumulation, most likely mediated by AMPK activation in the heart. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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14 pages, 2786 KiB

Open AccessArticle

Profiling of Low-Molecular-Weight Carbonyls and Protein Modifications in Flavored Milk

by Michele Wölk, Theres Schröter, Ralf Hoffmann and Sanja Milkovska-Stamenova

Antioxidants 2020, 9(11), 1169; https://doi.org/10.3390/antiox9111169 - 23 Nov 2020

Cited by 9 | Viewed by 2633

Abstract

Thermal treatments of dairy products favor oxidations, Maillard reactions, and the formation of sugar or lipid oxidation products. Additives including flavorings might enhance these reactions or even induce further reactions. Here we aimed to characterize protein modifications in four flavored milk drinks using [...] Read more.

Thermal treatments of dairy products favor oxidations, Maillard reactions, and the formation of sugar or lipid oxidation products. Additives including flavorings might enhance these reactions or even induce further reactions. Here we aimed to characterize protein modifications in four flavored milk drinks using samples along the production chain—raw milk, pasteurization, mixing with flavorings, heat treatment, and the commercial product. Therefore, milk samples were analyzed using a bottom up proteomics approach and a combination of data-independent (MS^E) and data-dependent acquisition methods (DDA). Twenty-one small carbonylated lipids were identified by shotgun lipidomics triggering 13 protein modifications. Additionally, two Amadori products, 12 advanced glycation end products (AGEs), and 12 oxidation-related modifications were targeted at the protein level. The most common modifications were lactosylation, formylation, and carboxymethylation. The numbers and distribution of modification sites present in raw milk remained stable after pasteurization and mixing with flavorings, while the final heat treatment significantly increased lactosylation and hexosylation in qualitative and quantitative terms. The processing steps did not significantly affect the numbers of AGE-modified, oxidized/carbonylated, and lipid-carbonylated sites in proteins. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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15 pages, 4357 KiB

Open AccessArticle

Adverse Effects of Methylglyoxal on Transcriptome and Metabolic Changes in Visceral Adipose Tissue in a Prediabetic Rat Model

by Martina Hüttl, Irena Markova, Denisa Miklankova, Pavol Makovicky, Terezie Pelikanova, Ondrej Šeda, Lucie Šedová and Hana Malinska

Antioxidants 2020, 9(9), 803; https://doi.org/10.3390/antiox9090803 - 31 Aug 2020

Cited by 7 | Viewed by 2809

Abstract

Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic [...] Read more.

Excessive methylglyoxal (MG) production contributes to metabolic and vascular changes by increasing inflammatory processes, disturbing regulatory mechanisms and exacerbating tissue dysfunction. MG accumulation in adipocytes leads to structural and functional changes. We used transcriptome analysis to investigate the effect of MG on metabolic changes in the visceral adipose tissue of hereditary hypetriglyceridaemic rats, a non-obese model of metabolic syndrome. Compared to controls, 4-week intragastric MG administration impaired glucose tolerance (p < 0.05) and increased glycaemia (p < 0.01) and serum levels of MCP-1 and TNFα (p < 0.05), but had no effect on serum adiponectin or leptin. Adipose tissue insulin sensitivity and lipolysis were impaired (p < 0.05) in MG-treated rats. In addition, MG reduced the expression of transcription factor Nrf2 (p < 0.01), which controls antioxidant and lipogenic genes. Increased expression of Mcp-1 and TNFα (p < 0.05) together with activation of the SAPK/JNK signaling pathway can promote chronic inflammation in adipose tissue. Transcriptome network analysis revealed the over-representation of genes involved in insulin signaling (Irs1, Igf2, Ide), lipid metabolism (Nr1d1, Lpin1, Lrpap1) and angiogenesis (Dusp10, Tp53inp1). Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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Review

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25 pages, 1921 KiB

Open AccessReview

Protein Lipoxidation: Basic Concepts and Emerging Roles

by Álvaro Viedma-Poyatos, Patricia González-Jiménez, Ophélie Langlois, Idoia Company-Marín, Corinne M. Spickett and Dolores Pérez-Sala

Antioxidants 2021, 10(2), 295; https://doi.org/10.3390/antiox10020295 - 16 Feb 2021

Cited by 25 | Viewed by 3690

Abstract

Protein lipoxidation is a non-enzymatic post-translational modification that consists of the covalent addition of reactive lipid species to proteins. This occurs under basal conditions but increases in situations associated with oxidative stress. Protein targets for lipoxidation include metabolic and signalling enzymes, cytoskeletal proteins, [...] Read more.

Protein lipoxidation is a non-enzymatic post-translational modification that consists of the covalent addition of reactive lipid species to proteins. This occurs under basal conditions but increases in situations associated with oxidative stress. Protein targets for lipoxidation include metabolic and signalling enzymes, cytoskeletal proteins, and transcription factors, among others. There is strong evidence for the involvement of protein lipoxidation in disease, including atherosclerosis, neurodegeneration, and cancer. Nevertheless, the involvement of lipoxidation in cellular regulatory mechanisms is less understood. Here we review basic aspects of protein lipoxidation and discuss several features that could support its role in cell signalling, including its selectivity, reversibility, and possibilities for regulation at the levels of the generation and/or detoxification of reactive lipids. Moreover, given the great structural variety of electrophilic lipid species, protein lipoxidation can contribute to the generation of multiple structurally and functionally diverse protein species. Finally, the nature of the lipoxidised proteins and residues provides a frameshift for a complex interplay with other post-translational modifications, including redox and redox-regulated modifications, such as oxidative modifications and phosphorylation, thus strengthening the importance of detailed knowledge of this process. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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30 pages, 1644 KiB

Open AccessReview

Protein Carbonylation and Lipid Peroxidation in Hematological Malignancies

by Alba Rodríguez-García, Roberto García-Vicente, María Luz Morales, Alejandra Ortiz-Ruiz, Joaquín Martínez-López and María Linares

Antioxidants 2020, 9(12), 1212; https://doi.org/10.3390/antiox9121212 - 01 Dec 2020

Cited by 33 | Viewed by 5387

Abstract

Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and [...] Read more.

Among the different mechanisms involved in oxidative stress, protein carbonylation and lipid peroxidation are both important modifications associated with the pathogenesis of several diseases, including cancer. Hematopoietic cells are particularly vulnerable to oxidative damage, as the excessive production of reactive oxygen species and associated lipid peroxidation suppress self-renewal and induce DNA damage and genomic instability, which can trigger malignancy. A richer understanding of the clinical effects of oxidative stress might improve the prognosis of these diseases and inform therapeutic strategies. The most common protein carbonylation and lipid peroxidation compounds, including hydroxynonenal, malondialdehyde, and advanced oxidation protein products, have been investigated for their potential effect on hematopoietic cells in several studies. In this review, we focus on the most important protein carbonylation and lipid peroxidation biomarkers in hematological malignancies, their role in disease development, and potential treatment implications. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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20 pages, 775 KiB

Open AccessEditor’s ChoiceReview

The Advanced Lipoxidation End-Product Malondialdehyde-Lysine in Aging and Longevity

by Mariona Jové, Natàlia Mota-Martorell, Irene Pradas, Meritxell Martín-Gari, Victoria Ayala and Reinald Pamplona

Antioxidants 2020, 9(11), 1132; https://doi.org/10.3390/antiox9111132 - 15 Nov 2020

Cited by 51 | Viewed by 5535

Abstract

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this [...] Read more.

The nonenzymatic adduction of malondialdehyde (MDA) to the protein amino groups leads to the formation of malondialdehyde-lysine (MDALys). The degree of unsaturation of biological membranes and the intracellular oxidative conditions are the main factors that modulate MDALys formation. The low concentration of this modification in the different cellular components, found in a wide diversity of tissues and animal species, is indicative of the presence of a complex network of cellular protection mechanisms that avoid its cytotoxic effects. In this review, we will focus on the chemistry of this lipoxidation-derived protein modification, the specificity of MDALys formation in proteins, the methodology used for its detection and quantification, the MDA-lipoxidized proteome, the metabolism of MDA-modified proteins, and the detrimental effects of this protein modification. We also propose that MDALys is an indicator of the rate of aging based on findings which demonstrate that (i) MDALys accumulates in tissues with age, (ii) the lower the concentration of MDALys the greater the longevity of the animal species, and (iii) its concentration is attenuated by anti-aging nutritional and pharmacological interventions. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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39 pages, 3806 KiB

Open AccessReview

A Comprehensive Review on Source, Types, Effects, Nanotechnology, Detection, and Therapeutic Management of Reactive Carbonyl Species Associated with Various Chronic Diseases

by Shivkanya Fuloria, Vetriselvan Subramaniyan, Sundram Karupiah, Usha Kumari, Kathiresan Sathasivam, Dhanalekshmi Unnikrishnan Meenakshi, Yuan Seng Wu, Rhanye Mac Guad, Kaviraja Udupa and Neeraj Kumar Fuloria

Antioxidants 2020, 9(11), 1075; https://doi.org/10.3390/antiox9111075 - 02 Nov 2020

Cited by 30 | Viewed by 4055

Abstract

Continuous oxidation of carbohydrates, lipids, and amino acids generate extremely reactive carbonyl species (RCS). Human body comprises some important RCS namely hexanal, acrolein, 4-hydroxy-2-nonenal, methylglyoxal, malondialdehyde, isolevuglandins, and 4-oxo-2- nonenal etc. These RCS damage important cellular components including proteins, nucleic acids, and lipids, [...] Read more.

Continuous oxidation of carbohydrates, lipids, and amino acids generate extremely reactive carbonyl species (RCS). Human body comprises some important RCS namely hexanal, acrolein, 4-hydroxy-2-nonenal, methylglyoxal, malondialdehyde, isolevuglandins, and 4-oxo-2- nonenal etc. These RCS damage important cellular components including proteins, nucleic acids, and lipids, which manifests cytotoxicity, mutagenicity, multitude of adducts and crosslinks that are connected to ageing and various chronic diseases like inflammatory disease, atherosclerosis, cerebral ischemia, diabetes, cancer, neurodegenerative diseases and cardiovascular disease. The constant prevalence of RCS in living cells suggests their importance in signal transduction and gene expression. Extensive knowledge of RCS properties, metabolism and relation with metabolic diseases would assist in development of effective approach to prevent numerous chronic diseases. Treatment approaches for RCS associated diseases involve endogenous RCS metabolizers, carbonyl metabolizing enzyme inducers, and RCS scavengers. Limited bioavailability and bio efficacy of RCS sequesters suggest importance of nanoparticles and nanocarriers. Identification of RCS and screening of compounds ability to sequester RCS employ several bioassays and analytical techniques. Present review describes in-depth study of RCS sources, types, properties, identification techniques, therapeutic approaches, nanocarriers, and their role in various diseases. This study will give an idea for therapeutic development to combat the RCS associated chronic diseases. Full article

(This article belongs to the Special Issue Reactive Carbonyl Species and Protein Adducts: Identification Strategies, Biological Mechanisms and Molecular Approaches for Their Detoxification)

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