The Redox Balance and Membrane Shedding in RBC Production, Maturation, and Senescence

Frontiers in Physiology ◽

10.3389/fphys.2021.604738 ◽

2021 ◽

Vol 12 ◽

Author(s):

Eitan Fibach

Keyword(s):

Oxidative Stress ◽

Blood Cells ◽

Redox System ◽

Redox Balance ◽

Reticuloendothelial System ◽

Cellular Processes ◽

Membrane Cytoskeleton ◽

Intracellular Ca ◽

Membrane Shedding ◽

Cellular Components

Membrane shedding in the form of extracellular vesicles plays a key role in normal physiology and pathology. Partial disturbance of the membrane–cytoskeleton linkage and increased in the intracellular Ca content are considered to be mechanisms underlying the process, but it is questionable whether they constitute the primary initiating steps. Homeostasis of the redox system, which depends on the equilibrium between oxidants and antioxidants, is crucial for many cellular processes. Excess oxidative power results in oxidative stress, which affects many cellular components, including the membrane. Accumulating evidence suggests that oxidative stress indirectly affects membrane shedding most probably by affecting the membrane–cytoskeleton and the Ca content. In red blood cells (RBCs), changes in both the redox system and membrane shedding occur throughout their life—from birth—their production in the bone marrow, to death—aging in the peripheral blood and removal by macrophages in sites of the reticuloendothelial system. Both oxidative stress and membrane shedding are disturbed in diseases affecting the RBC, such as the hereditary and acquired hemolytic anemias (i.e., thalassemia, sickle cell anemia, and autoimmune hemolytic anemia). Herein, I review some data-based and hypothetical possibilities that await experimental confirmation regarding some aspects of the interaction between the redox system and membrane shedding and its role in the normal physiology and pathology of RBCs.

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Methodologies to Assess the Bioactivity of an Herbal Extract on Immunity, Health, Welfare and Production Performance in the Chicken: The Case of Melissa officinalis L. Extract

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.759456 ◽

2021 ◽

Vol 8 ◽

Author(s):

Angélique Travel ◽

Angélique Petit ◽

Perrine Barat ◽

Anne Collin ◽

Camille Bourrier-Clairat ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Cells ◽

Ex Vivo ◽

Redox Balance ◽

Herbal Extracts ◽

Melissa Officinalis ◽

Starting Conditions ◽

Anti Inflammatory ◽

And Oxidative Stress

The potential of herbal extracts containing bioactive compounds to strengthen immunity could contribute to reducing antimicrobial use in poultry. This study aimed at developing a reliable and robust methodological pipeline to assess the ability of herbal extracts to strengthen chicken innate defenses, especially concerning inflammation and oxidative stress. This methodology was applied to Melissa officinalis L. (MEL) extract, recognized for its biological activities including antioxidant and anti-inflammatory properties. Different methods were used to (1). guarantee the quality of MEL extract and its capacity to stimulate the innate immune system; (2). evaluate the relevance of an ex vivo model to mimic inflammatory and oxidative stress challenges to replace LPS injection in chickens; (3). analyse the effects of feed supplemented with MEL extract on inflammation and oxidative stress induced ex vivo; (4). assess the effects of MEL extract on the redox balance, health, welfare and performance in broilers exposed to suboptimal starting conditions through a large-scale approach. The quality of MEL extract preparations, through phytochemical quantification of rosmarinic acid (RA), revealed varying concentrations of RA in the different MEL extracts. RA concentrations remained stable for at least 9 months and in feed three months after incorporating MEL extract. When incubated with chicken cell lines MEL extract showed potential metabolic activation and ability to stimulate immune functions but induced cytotoxicity at high concentrations. The original ex vivo model of inflammation developed on chicken blood cells enabled inflammation and oxidative stress biomarkers to be expressed and revealed antioxidative and anti-inflammatory properties of blood cells from chickens fed MEL extract. The experimental model of chicken suboptimal starting conditions validated beneficial effects of MEL extract on the redox balance and also evidenced improved performance during the growth phase, a tendency for fewer muscle defects but a higher severity of pododermatitis lesions without affecting other welfare indicators. This study grouped methods and tools that could be combined according to the plant extract, the needs of professionals working in poultry production systems and staff responsible for animal health, welfare and feeding.

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Antioxidant Roles of SGLT2 Inhibitors in the Kidney

Biomolecules ◽

10.3390/biom12010143 ◽

2022 ◽

Vol 12 (1) ◽

pp. 143

Author(s):

Carmen Llorens-Cebrià ◽

Mireia Molina-Van den Bosch ◽

Ander Vergara ◽

Conxita Jacobs-Cachá ◽

Maria José Soler

Keyword(s):

Oxidative Stress ◽

Cell Function ◽

Redox System ◽

High Energy ◽

Sglt2 Inhibitors ◽

Enzymatic Reactions ◽

Cellular Processes ◽

Proximal Tubular ◽

Antioxidant Mechanisms

The reduction-oxidation (redox) system consists of the coupling and coordination of various electron gradients that are generated thanks to serial reduction-oxidation enzymatic reactions. These reactions happen in every cell and produce radical oxidants that can be mainly classified into reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS modulate cell-signaling pathways and cellular processes fundamental to normal cell function. However, overproduction of oxidative species can lead to oxidative stress (OS) that is pathological. Oxidative stress is a main contributor to diabetic kidney disease (DKD) onset. In the kidney, the proximal tubular cells require a high energy supply to reabsorb proteins, metabolites, ions, and water. In a diabetic milieu, glucose-induced toxicity promotes oxidative stress and mitochondrial dysfunction, impairing tubular function. Increased glucose level in urine and ROS enhance the activity of sodium/glucose co-transporter type 2 (SGLT2), which in turn exacerbates OS. SGLT2 inhibitors have demonstrated clear cardiovascular benefits in DKD which may be in part ascribed to the generation of a beneficial equilibrium between oxidant and antioxidant mechanisms.

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Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes

Biochemistry and Cell Biology ◽

10.1139/bcb-2016-0048 ◽

2016 ◽

Vol 94 (5) ◽

pp. 471-479 ◽

Cited By ~ 26

Author(s):

Abhishek Kumar Singh ◽

Sandeep Singh ◽

Geetika Garg ◽

Syed Ibrahim Rizvi

Keyword(s):

Oxidative Stress ◽

Defense Mechanism ◽

Osmotic Fragility ◽

Redox System ◽

Protein Carbonyl ◽

Ros Production ◽

Rat Erythrocytes ◽

Immunosuppressant Drug ◽

Reducing Ability ◽

Intracellular Ca

An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl2 (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca2+ influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl2. Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl2-induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca2+ influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.

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Redox Imbalance in T Cell-Mediated Skin Diseases

Mediators of Inflammation ◽

10.1155/2010/861949 ◽

2010 ◽

Vol 2010 ◽

pp. 1-9 ◽

Cited By ~ 30

Author(s):

Saveria Pastore ◽

Liudmila Korkina

Keyword(s):

Oxidative Stress ◽

Atopic Dermatitis ◽

Contact Dermatitis ◽

Skin Diseases ◽

Redox Balance ◽

Inflammatory Disorder ◽

Chronic Inflammatory Disorder ◽

Physical Chemical ◽

Chemical Oxidants ◽

Beneficial Outcome

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.

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Short-term Effects of Metformin on Cardiac and Peripheral Blood Cells Following Cecal Ligation and Puncture-induced Sepsis

Drug Research ◽

10.1055/a-1322-7478 ◽

2020 ◽

Author(s):

Tina Didari ◽

Shokoufeh Hassani ◽

Maryam Baeeri ◽

Mona Navaei-Nigjeh ◽

Mahban Rahimifard ◽

...

Keyword(s):

Oxidative Stress ◽

Weight Loss ◽

Blood Cells ◽

Cell Injury ◽

Antioxidant Properties ◽

Cecal Ligation ◽

Neutrophil Infiltration ◽

Cardiac Cells ◽

Cecal Ligation And Puncture ◽

Blood Profile

Abstract Aim of the study Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis. Methods For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted. Results In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group. Conclusions Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.

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Overexpression of DUF538 from Wild Arachis Enhances Plant Resistance to Meloidogyne spp.

Agronomy ◽

10.3390/agronomy11030559 ◽

2021 ◽

Vol 11 (3) ◽

pp. 559

Author(s):

Ana Claudia Guerra Araujo ◽

Patricia Messenberg Guimaraes ◽

Ana Paula Zotta Mota ◽

Larissa Arrais Guimaraes ◽

Bruna Medeiros Pereira ◽

...

Keyword(s):

Transgenic Plants ◽

Redox System ◽

Redox Balance ◽

Uncharacterized Protein ◽

Chlorophyll Breakdown ◽

Domain Of Unknown Function ◽

Expression Behavior ◽

Meloidogyne Spp ◽

Wild Peanut ◽

First Time

DUF538 proteins belong to a large group of uncharacterized protein families sharing the highly conserved Domain of Unknown Function (DUF). Attention has been given to DUF538 domain-containing proteins due to changes in their gene expression behavior and protein abundance during plant development and responses to stress. Putative roles attributed to DUF538 in plants under abiotic and biotic constraints include involvement in cell redox balance, chlorophyll breakdown and pectin degradation. Our previous transcriptome studies suggested that DUF538 is also involved in the resistance responses of wild Arachis species against the highly hazardous root-knot nematodes (RKNs). To clarify the role of the AsDUF538 gene from the wild peanut relative Arachis stenosperma in this interaction, we analyzed the effect of its overexpression on RKN infection in peanut and soybean hairy roots and Arabidopsis transgenic plants. AsDUF538 overexpression significantly reduced the infection in all three heterologous plant systems against their respective RKN counterparts. The distribution of AsDUF538 transcripts in RKN-infected Arachis roots and the effects of AsDUF538 overexpression on hormonal pathways and redox system in transgenic Arabidopsis were also evaluated. This is the first time that a DUF538 gene is functionally validated in transgenic plants and the earliest report on its role in plant defense against RKNs.

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An unusual thioredoxin system in the facultative parasite Acanthamoeba castellanii

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-03786-x ◽

2021 ◽

Vol 78 (7) ◽

pp. 3673-3689

Author(s):

David Leitsch ◽

Alvie Loufouma Mbouaka ◽

Martina Köhsler ◽

Norbert Müller ◽

Julia Walochnik

Keyword(s):

Oxidative Stress ◽

Stop Codon ◽

Acanthamoeba Castellanii ◽

Methionine Sulfoxide ◽

Redox System ◽

Methionine Sulfoxide Reductase ◽

Methionine Sulfoxide Reductase A ◽

Protein Levels ◽

Thioredoxin System ◽

Facultative Parasite

AbstractThe free-living amoeba Acanthamoeba castellanii occurs worldwide in soil and water and feeds on bacteria and other microorganisms. It is, however, also a facultative parasite and can cause serious infections in humans. The annotated genome of A. castellanii (strain Neff) suggests the presence of two different thioredoxin reductases (TrxR), of which one is of the small bacterial type and the other of the large vertebrate type. This combination is highly unusual. Similar to vertebrate TrxRases, the gene coding for the large TrxR in A. castellanii contains a UGA stop codon at the C-terminal active site, suggesting the presence of selenocysteine. We characterized the thioredoxin system in A. castellanii in conjunction with glutathione reductase (GR), to obtain a more complete understanding of the redox system in A. castellanii and the roles of its components in the response to oxidative stress. Both TrxRases localize to the cytoplasm, whereas GR localizes to the cytoplasm and the large organelle fraction. We could only identify one thioredoxin (Trx-1) to be indeed reduced by one of the TrxRases, i.e., by the small TrxR. This thioredoxin, in turn, could reduce one of the two peroxiredoxins tested and also methionine sulfoxide reductase A (MsrA). Upon exposure to hydrogen peroxide and diamide, only the small TrxR was upregulated in expression at the mRNA and protein levels, but not the large TrxR. Our results show that the small TrxR is involved in the A. castellanii’s response to oxidative stress. The role of the large TrxR, however, remains elusive.

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Regulation of intracellular glutathione levels in erythrocytes infected with chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

Biochemical Journal ◽

10.1042/bj20020962 ◽

2002 ◽

Vol 368 (3) ◽

pp. 761-768 ◽

Cited By ~ 73

Author(s):

Svenja MEIERJOHANN ◽

Rolf D. WALTER ◽

Sylke MÜLLER

Keyword(s):

Oxidative Stress ◽

Red Blood Cells ◽

Blood Cells ◽

Differential Susceptibility ◽

Protozoan Parasite ◽

Chloroquine Resistance ◽

Glutathione Metabolism ◽

Glutathione Synthesis ◽

Intracellular Glutathione ◽

Glutamylcysteine Synthetase

Malaria is one of the most devastating tropical diseases despite the availability of numerous drugs acting against the protozoan parasite Plasmodium in its human host. However, the development of drug resistance renders most of the existing drugs useless. In the malaria parasite the tripeptide glutathione is not only involved in maintaining an adequate intracellular redox environment and protecting the cell against oxidative stress, but it has also been shown that it degrades non-polymerized ferriprotoporphyrin IX (FP IX) and is thus implicated in the development of chloroquine resistance. Glutathione levels in Plasmodium-infected red blood cells are regulated by glutathione synthesis, glutathione reduction and glutathione efflux. Therefore the effects of drugs that interfere with these metabolic processes were studied to establish possible differences in the regulation of the glutathione metabolism of a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodiumfalciparum. Growth inhibition of P. falciparum 3D7 by d,l-buthionine-(S,R)sulphoximine (BSO), an inhibitor of γ-glutamylcysteine synthetase (γ-GCS), and by Methylene Blue (MB), an inhibitor of gluta thione reductase (GR), was significantly more pronounced than inhibition of P.falciparum Dd2 growth by these drugs. These results correlate with the higher levels of total glutathione in P. falciparum Dd2. Short-term incubations of Percoll-enriched trophozoite-infected red blood cells in the presence of BSO, MB and N,N1-bis(2-chloroethyl)-N-nitrosourea and subsequent determinations of γ-GCS activities, GR activities and glutathione disulphide efflux revealed that maintenance of intracellular glutathione in P. falciparum Dd2 is mainly dependent on glutathione synthesis whereas in P. falciparum 3D7 it is regulated via GR. Generally, P. falciparum Dd2 appears to be able to sustain its intracellular glutathione more efficiently than P. falciparum 3D7. In agreement with these findings is the differential susceptibility to oxidative stress of both parasite strains elicited by the glucose/glucose oxidase system.

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