Involvement of the MetO/Msr System in Two Acer Species That Display Contrasting Characteristics during Germination

The levels of methionine sulfoxide (MetO) and the abundances of methionine sulfoxide reductases (Msrs) were reported as important for the desiccation tolerance of Acer seeds. To determine whether the MetO/Msrs system is related to reactive oxygen species (ROS) and involved in the regulation of germination in orthodox and recalcitrant seeds, Norway maple and sycamore were investigated. Changes in water content, MetO content, the abundance of MsrB1 and MsrB2 in relation to ROS content and the activity of reductases depending on nicotinamide adenine dinucleotides were monitored. Acer seeds differed in germination speed—substantially higher in sycamore—hydration dynamics, levels of hydrogen peroxide, superoxide anion radicals (O2•−) and hydroxyl radicals (•OH), which exhibited peaks at different stages of germination. The MetO level dynamically changed, particularly in sycamore embryonic axes, where it was positively correlated with the levels of O2•− and the abundance of MsrB1 and negatively with the levels of •OH and the abundance of MsrB2. The MsrB2 abundance increased upon sycamore germination; in contrast, it markedly decreased in Norway maple. We propose that the ROS–MetO–Msr redox system, allowing balanced Met redox homeostasis, participates in the germination process in sycamore, which is characterized by a much higher speed compared to Norway maple.

Download Full-text

Peptide-Bound Methionine Sulfoxide (MetO) Levels and MsrB2 Abundance Are Differentially Regulated during the Desiccation Phase in Contrasted Acer Seeds

Antioxidants ◽

10.3390/antiox9050391 ◽

2020 ◽

Vol 9 (5) ◽

pp. 391 ◽

Cited By ~ 3

Author(s):

Natalia Wojciechowska ◽

Shirin Alipour ◽

Ewelina Stolarska ◽

Karolina Bilska ◽

Pascal Rey ◽

...

Keyword(s):

Desiccation Tolerance ◽

Methionine Sulfoxide ◽

Redox Status ◽

Embryonic Axes ◽

Seed Desiccation ◽

Methionine Sulfoxide Reductases ◽

Norway Maple ◽

Orthodox Seeds ◽

Oxidation Of Methionine ◽

Reduced Forms

Norway maple and sycamore produce desiccation-tolerant (orthodox) and desiccation-sensitive (recalcitrant) seeds, respectively. Drying affects reduction and oxidation (redox) status in seeds. Oxidation of methionine to methionine sulfoxide (MetO) and reduction via methionine sulfoxide reductases (Msrs) have never been investigated in relation to seed desiccation tolerance. MetO levels and the abundance of Msrs were investigated in relation to levels of reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion radical and hydroxyl radical (•OH), and the levels of ascorbate and glutathione redox couples in gradually dried seeds. Peptide-bound MetO levels were positively correlated with ROS concentrations in the orthodox seeds. In particular, •OH affected MetO levels as well as the abundance of MsrB2 solely in the embryonic axes of Norway maple seeds. In this species, MsrB2 was present in oxidized and reduced forms, and the latter was favored by reduced glutathione and ascorbic acid. In contrast, sycamore seeds accumulated higher ROS levels. Additionally, MsrB2 was oxidized in sycamore throughout dehydration. In this context, the three elements •OH level, MetO content and MsrB2 abundance, linked together uniquely to Norway maple seeds, might be considered important players of the redox network associated with desiccation tolerance.

Download Full-text

Role of mitochondrial superoxide dismutase in contraction-induced generation of reactive oxygen species in skeletal muscle extracellular space

AJP Cell Physiology ◽

10.1152/ajpcell.00322.2003 ◽

2004 ◽

Vol 286 (5) ◽

pp. C1152-C1158 ◽

Cited By ~ 51

Author(s):

A. McArdle ◽

J. van der Meulen ◽

G. L. Close ◽

D. Pattwell ◽

H. Van Remmen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Hydroxyl Radical ◽

Hydroxyl Radicals ◽

Extracellular Space ◽

Superoxide Anion ◽

Reactive Oxygen ◽

Oxygen Species ◽

Superoxide Anions ◽

Wild Type ◽

Mnsod Activity

Contractions of skeletal muscles produce increases in concentrations of superoxide anions and activity of hydroxyl radicals in the extracellular space. The sources of these reactive oxygen species are not clear. We tested the hypothesis that, after a demanding isometric contraction protocol, the major source of superoxide and hydroxyl radical activity in the extracellular space of muscles is mitochondrial generation of superoxide anions and that, with a reduction in MnSOD activity, concentration of superoxide anions in the extracellular space is unchanged but concentration of hydroxyl radicals is decreased. For gastrocnemius muscles from adult (6–8 mo old) wild-type ( Sod2+/+) mice and knockout mice heterozygous for the MnSOD gene ( Sod2+/-), concentrations of superoxide anions and hydroxyl radical activity were measured in the extracellular space by microdialysis. A 15-min protocol of 180 isometric contractions induced a rapid, equivalent increase in reduction of cytochrome c as an index of superoxide anion concentrations in the extracellular space of Sod2+/+ and Sod2+/- mice, whereas hydroxyl radical activity measured by formation of 2,3-dihydroxybenzoate from salicylate increased only in the extracellular space of muscles of Sod2+/+ mice. The lack of a difference in increase in superoxide anion concentration in the extracellular space of Sod2+/+ and Sod2+/- mice after the contraction protocol supported the hypothesis that superoxide anions were not directly derived from mitochondria. In contrast, the data obtained suggest that the increase in hydroxyl radical concentration in the extracellular space of muscles from wild-type mice after the contraction protocol most likely results from degradation of hydrogen peroxide generated by MnSOD activity.

Download Full-text

Localization and Dynamics of the Methionine Sulfoxide Reductases MsrB1 and MsrB2 in Beech Seeds

International Journal of Molecular Sciences ◽

10.3390/ijms22010402 ◽

2021 ◽

Vol 22 (1) ◽

pp. 402

Author(s):

Natalia Wojciechowska ◽

Agnieszka Bagniewska-Zadworna ◽

Julia Minicka ◽

Kornel M. Michalak ◽

Ewa M. Kalemba

Keyword(s):

Stress Responses ◽

Management Practices ◽

Seed Viability ◽

Methionine Sulfoxide ◽

Embryonic Axes ◽

Long Term Storage ◽

Protein Storage Vacuoles ◽

Methionine Sulfoxide Reductases ◽

Term Storage

Beech seeds are produced irregularly, and there is a need for long-term storage of these seeds for forest management practices. Accumulated reactive oxygen species broadly oxidize molecules, including amino acids, such as methionine, thereby contributing to decreased seed viability. Methionine oxidation can be reversed by the activity of methionine sulfoxide reductases (Msrs), which are enzymes involved in the regulation of many developmental processes and stress responses. Two types of Msrs, MsrB1 and MsrB2, were investigated in beech seeds to determine their abundance and localization. MsrB1 and MsrB2 were detected in the cortical cells and the outer area of the vascular cylinder of the embryonic axes as well as in the epidermis and parenchyma cells of cotyledons. The abundances of MsrB1 and MsrB2 decreased during long-term storage. Ultrastructural analyses have demonstrated the accumulation of these proteins in protein storage vacuoles and in the cytoplasm, especially in close proximity to the cell membrane. In silico predictions of possible Msr interactions supported our findings. In this study, we investigate the contribution of MsrB1 and MsrB2 locations in the regulation of seed viability and suggest that MsrB2 is linked with the longevity of beech seeds via association with proper utilization of storage material.

Download Full-text

Trypanothione metabolism as Drug Target for Trypanosomatids.

Current Pharmaceutical Design ◽

10.2174/1381612826666201211115329 ◽

2020 ◽

Vol 26 ◽

Author(s):

María Dolores Piñeyro ◽

Diego G Arias ◽

Adriana Parodi-Talice ◽

Sergio A Guerrero ◽

Carlos Robello

Keyword(s):

Methionine Sulfoxide ◽

Structural Data ◽

Redox System ◽

Redox Balance ◽

Rational Drug Design ◽

Sufficient Evidence ◽

Mammalian Host ◽

Neglected Diseases ◽

High Toxicity ◽

Methionine Sulfoxide Reductases

: Chagas Disease, African sleeping sickness, and leishmaniasis are neglected diseases caused by pathogenic trypanosomatid parasites, which have a considerable impact on morbidity and mortality in poor countries. The available drugs used as treatment have high toxicity, limited access, and can cause parasite drug resistance. Long-term treatments, added to their high toxicity, result in patients that give up therapy. Trypanosomatids presents a unique trypanothione based redox system, which is the main responsible for maintaining the redox balance. Therefore, inhibition of these essential and exclusive parasite’s metabolic pathways, absent from the mammalian host, could lead to development of more efficient and safe drugs. The system contains different redox cascades, where trypanothione and tryparedoxins, play together a central role in transferring reduced power to different enzymes, such as 2-Cys peroxiredoxins, non-selenium glutathione peroxidases, ascorbate peroxidases, glutaredoxins and methionine sulfoxide reductases, through NADPH as a source of electrons. There is sufficient evidence that this complex system is essential for parasite survival and infection. In this review, we explore what is known in terms of essentiality, kinetic and structural data, and development of inhibitors of enzymes from this trypanothione-based redox system. The recent advances and limitations in the development of lead inhibitory compounds targeting these enzymes are discussed. The combination of molecular biology, bioinformatics, genomics, and structural biology is fundamental since the knowledge of unique features of the trypanothione-dependent system will provide tools for rational drug design, in order to develop better treatments for these diseases

Download Full-text

The Oxidized Protein Repair Enzymes Methionine Sulfoxide Reductases and Their Roles in Protecting against Oxidative Stress, in Ageing and in Regulating Protein Function

Antioxidants ◽

10.3390/antiox7120191 ◽

2018 ◽

Vol 7 (12) ◽

pp. 191 ◽

Cited By ~ 9

Author(s):

Sofia Lourenço dos Santos ◽

Isabelle Petropoulos ◽

Bertrand Friguet

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Protein Function ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductase ◽

Methionine Oxidation ◽

Oxygen Species ◽

Sulfenic Acid ◽

Protein Repair ◽

Methionine Sulfoxide Reductases

Cysteine and methionine residues are the amino acids most sensitive to oxidation by reactive oxygen species. However, in contrast to other amino acids, certain cysteine and methionine oxidation products can be reduced within proteins by dedicated enzymatic repair systems. Oxidation of cysteine first results in either the formation of a disulfide bridge or a sulfenic acid. Sulfenic acid can be converted to disulfide or sulfenamide or further oxidized to sulfinic acid. Disulfide can be easily reversed by different enzymatic systems such as the thioredoxin/thioredoxin reductase and the glutaredoxin/glutathione/glutathione reductase systems. Methionine side chains can also be oxidized by reactive oxygen species. Methionine oxidation, by the addition of an extra oxygen atom, leads to the generation of methionine sulfoxide. Enzymatically catalyzed reduction of methionine sulfoxide is achieved by either methionine sulfoxide reductase A or methionine sulfoxide reductase B, also referred as to the methionine sulfoxide reductases system. This oxidized protein repair system is further described in this review article in terms of its discovery and biologically relevant characteristics, and its important physiological roles in protecting against oxidative stress, in ageing and in regulating protein function.

Download Full-text

Methionine Sulfoxide Reductases of Archaea

Antioxidants ◽

10.3390/antiox7100124 ◽

2018 ◽

Vol 7 (10) ◽

pp. 124 ◽

Cited By ~ 7

Author(s):

Julie Maupin-Furlow

Keyword(s):

Hydrothermal Vents ◽

Methionine Sulfoxide ◽

Oxygen Species ◽

Protein Targets ◽

Methionine Sulfoxide Reductases ◽

Low Concentrations ◽

Evolutionarily Conserved ◽

Domains Of Life ◽

And Function ◽

Sulfur Containing

Methionine sulfoxide reductases are found in all domains of life and are important in reversing the oxidative damage of the free and protein forms of methionine, a sulfur containing amino acid particularly sensitive to reactive oxygen species (ROS). Archaea are microbes of a domain of life distinct from bacteria and eukaryotes. Archaea are well known for their ability to withstand harsh environmental conditions that range from habitats of high ROS, such as hypersaline lakes of intense ultraviolet (UV) radiation and desiccation, to hydrothermal vents of low concentrations of dissolved oxygen at high temperature. Recent evidence reveals the methionine sulfoxide reductases of archaea function not only in the reduction of methionine sulfoxide but also in the ubiquitin-like modification of protein targets during oxidative stress, an association that appears evolutionarily conserved in eukaryotes. Here is reviewed methionine sulfoxide reductases and their distribution and function in archaea.

Download Full-text

Dietary Oxidative Distress: A Review of Nutritional Challenges as Models for Poultry, Swine and Fish

Antioxidants ◽

10.3390/antiox10040525 ◽

2021 ◽

Vol 10 (4) ◽

pp. 525

Author(s):

Elodie Bacou ◽

Carrie Walk ◽

Sebastien Rider ◽

Gilberto Litta ◽

Estefania Perez-Calvo

Keyword(s):

Redox Homeostasis ◽

Redox System ◽

Fats And Oils ◽

Feed Additives ◽

Farm Animals ◽

Oxygen Species ◽

Productive Performance ◽

Meal Protein ◽

Feeding Diets ◽

Systemic Responses

The redox system is essential for maintaining cellular homeostasis. When redox homeostasis is disrupted through an increase of reactive oxygen species or a decrease of antioxidants, oxidative distress occurs resulting in multiple tissue and systemic responses and damage. Poultry, swine and fish, raised in commercial conditions, are exposed to different stressors that can affect their productivity. Some dietary stressors can generate oxidative distress and alter the health status and subsequent productive performance of commercial farm animals. For several years, researchers used different dietary stressors to describe the multiple and detrimental effects of oxidative distress in animals. Some of these dietary challenge models, including oxidized fats and oils, exposure to excess heavy metals, soybean meal, protein or amino acids, and feeding diets contaminated with mycotoxins are discussed in this review. A better understanding of the oxidative distress mechanisms associated with dietary stressors allows for improved understanding and evaluation of feed additives as mitigators of oxidative distress.

Download Full-text

Methionine Redox Homeostasis in Protein Quality Control

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.665492 ◽

2021 ◽

Vol 8 ◽

Author(s):

Laurent Aussel ◽

Benjamin Ezraty

Keyword(s):

Oxidative Stress ◽

Quality Control ◽

Protein Function ◽

Protein Quality ◽

Redox Homeostasis ◽

Protein Quality Control ◽

Methionine Sulfoxide ◽

Methionine Sulfoxide Reductases ◽

Methionine Residues ◽

And Function

Bacteria live in different environments and are subject to a wide variety of fluctuating conditions. During evolution, they acquired sophisticated systems dedicated to maintaining protein structure and function, especially during oxidative stress. Under such conditions, methionine residues are converted into methionine sulfoxide (Met-O) which can alter protein function. In this review, we focus on the role in protein quality control of methionine sulfoxide reductases (Msr) which repair oxidatively protein-bound Met-O. We discuss our current understanding of the importance of Msr systems in rescuing protein function under oxidative stress and their ability to work in coordination with chaperone networks. Moreover, we highlight that bacterial chaperones, like GroEL or SurA, are also targeted by oxidative stress and under the surveillance of Msr. Therefore, integration of methionine redox homeostasis in protein quality control during oxidative stress gives a complete picture of this bacterial adaptive mechanism.

Download Full-text

Integration of MsrB1 and MsrB2 in the Redox Network during the Development of Orthodox and Recalcitrant Acer Seeds

Antioxidants ◽

10.3390/antiox9121250 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1250

Author(s):

Ewelina Stolarska ◽

Karolina Bilska ◽

Natalia Wojciechowska ◽

Agnieszka Bagniewska-Zadworna ◽

Pascal Rey ◽

...

Keyword(s):

Nicotinamide Adenine Dinucleotide ◽

Methionine Sulfoxide ◽

Redox Status ◽

Acer Pseudoplatanus ◽

Acer Platanoides ◽

Cellular Redox ◽

Methionine Sulfoxide Reductases ◽

Norway Maple ◽

Cellular Redox Environment ◽

Cell Redox Status

Two related tree species, Norway maple (Acer platanoides L.) and sycamore (Acer pseudoplatanus L.), produce desiccation-tolerant (orthodox) and desiccation-sensitive (recalcitrant) seeds, respectively. We compared the seeds of these two species to characterize the developmentally driven changes in the levels of peptide-bound methionine sulfoxide (MetO) and the abundance of methionine sulfoxide reductases (Msrs) B1 and B2, with respect to the cellular redox environment. Protein oxidation at the Met level was dynamic only in Norway maple seeds, and the reduced MsrB2 form was detected only in this species. Cell redox status, characterized by the levels of reduced and oxidized ascorbate, glutathione, and nicotinamide adenine dinucleotide (NAD)/phosphate (NADP), was clearly more reduced in the Norway maple seeds than in the sycamore seeds. Clear correlations between MetO levels, changes in water content and redox status were reported in orthodox Acer seeds. The abundance of Msrs was correlated in both species with redox determinants, mainly ascorbate and glutathione. Our data suggest that MsrB2 is associated with the acquisition of desiccation tolerance and that ascorbate might be involved in the redox pathway enabling the regeneration of Msr via intermediates that are not known yet.

Download Full-text

Protein Formulations Containing Polysorbates: Are Metal Chelators Needed at All?

Antioxidants ◽

10.3390/antiox9050441 ◽

2020 ◽

Vol 9 (5) ◽

pp. 441 ◽

Cited By ~ 3

Author(s):

Ema Valentina Brovč ◽

Stane Pajk ◽

Roman Šink ◽

Janez Mravljak

Keyword(s):

Reactive Oxygen Species ◽

Hydroxyl Radicals ◽

Ethylenediaminetetraacetic Acid ◽

Peptide Mapping ◽

Reactive Oxygen ◽

Redox System ◽

Oxygen Species ◽

Post Translational Modifications ◽

Catalysed Oxidation ◽

Reduced Rate

Proteins are prone to post-translational modifications at specific sites, which can affect their physicochemical properties, and consequently also their safety and efficacy. Sources of post-translational modifications include oxygen and reactive oxygen species. Additionally, catalytic amounts of Fe(II) or Cu(I) can promote increased activities of reactive oxygen species, and thus catalyse the production of particularly reactive hydroxyl radicals. When oxidative post-translational modifications are detected in the biopharmaceutical industry, it is common practice to add chelators to the formulation. However, the resultant complexes with metals can be even more damaging. Indeed, this is supported here using an ascorbate redox system assay and peptide mapping. Ethylenediaminetetraacetic acid (EDTA) addition strongly accelerated the formation of hydroxyl radicals in an iron-ascorbate system, while diethylenetriaminepentaacetic acid (DTPA) addition did not. When Fe(III) was substituted with Cu(II), EDTA addition almost stopped hydroxyl radical production, whereas DTPA addition showed continued production, but at a reduced rate. Further, EDTA accelerated metal-catalysed oxidation of proteins, and thus did not protect them from Fe-mediated oxidative damage. As every formulation is unique, justification for EDTA or DTPA addition should be based on experimental data and not common practice.

Download Full-text