scholarly journals Looking Back at the Early Stages of Redox Biology

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1254
Author(s):  
Leopold Flohé
Keyword(s):  
Hydrogen Peroxide ◽  
Metabolic Regulation ◽  
Redox Regulation ◽  
Biological Systems ◽  
Nitrogen Monoxide ◽  
Lipid Hydroperoxides ◽  
Redox Biology ◽  
Glutathione Peroxidases ◽  
And Function ◽  
Heme Peroxidases

The beginnings of redox biology are recalled with special emphasis on formation, metabolism and function of reactive oxygen and nitrogen species in mammalian systems. The review covers the early history of heme peroxidases and the metabolism of hydrogen peroxide, the discovery of selenium as integral part of glutathione peroxidases, which expanded the scope of the field to other hydroperoxides including lipid hydroperoxides, the discovery of superoxide dismutases and superoxide radicals in biological systems and their role in host defense, tissue damage, metabolic regulation and signaling, the identification of the endothelial-derived relaxing factor as the nitrogen monoxide radical (more commonly named nitric oxide) and its physiological and pathological implications. The article highlights the perception of hydrogen peroxide and other hydroperoxides as signaling molecules, which marks the beginning of the flourishing fields of redox regulation and redox signaling. Final comments describe the development of the redox language. In the 18th and 19th century, it was highly individualized and hard to translate into modern terminology. In the 20th century, the redox language co-developed with the chemical terminology and became clearer. More recently, the introduction and inflationary use of poorly defined terms has unfortunately impaired the understanding of redox events in biological systems.

scholarly journals Looking Back at the Early Times of Redox Biology

2020 ◽  
Author(s):  
Leopold Flohe
Keyword(s):  
Hydrogen Peroxide ◽  
Metabolic Regulation ◽  
Redox Regulation ◽  
Biological Systems ◽  
Lipid Hydroperoxide ◽  
Nitrogen Monoxide ◽  
Redox Biology ◽  
Glutathione Peroxidases ◽  
And Function ◽  
Heme Peroxidases

The beginnings of redox biology are recalled with special emphasis on formation, metabolism and function of reactive oxygen and nitrogen species in mammalian systems. The review covers the early history of heme peroxidases and the metabolism of hydrogen peroxide, the discovery of selenium as integral part of glutathione peroxidases, which expanded the scope of the field to other hydroperoxides including lipid hydroperoxide, the discovery of superoxide dismutases and superoxide radicals in biological systems and their role in host defense, tissue damage, metabolic regulation and signaling, the identification of the endothelial-derived relaxing factor as the nitrogen monoxide radical and its physiological and pathological implications. The article highlights the perception of hydrogen peroxide and other hydroperoxides as signaling molecules, which marks the beginning of the flourishing fields of redox regulation and redox signaling. Final comments describe the development of the redox language. In the 18th and 19th century, it was highly individualized and hard to translate into modern terminology. In the 20th century, the redox language co-developed with the chemical terminology and became clearer. More recently, the introduction and inflationary use of poorly defined terms has unfortunately impaired the understanding of redox events in biological systems.

scholarly journals Selenium-Catalyzed Reduction of Hydroperoxides in Chemistry and Biology

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1560
Author(s):  
Laura Orian ◽  
Leopold Flohé
Keyword(s):  
Metabolic Regulation ◽  
Redox Regulation ◽  
Antioxidant Defense ◽  
Catalytic Efficiency ◽  
Antioxidant Defense System ◽  
Nucleophilic Attack ◽  
Glutathione Peroxidases ◽  
H2o2 Reduction ◽  
Thioredoxin Reductases ◽  
Peroxide Bond

Among the chalcogens, selenium is the key element for catalyzed H2O2 reduction. In organic synthesis, catalytic amounts of organo mono- and di-selenides are largely used in different classes of oxidations, in which H2O2 alone is poorly efficient. Biological hydroperoxide metabolism is dominated by peroxidases and thioredoxin reductases, which balance hydroperoxide challenge and contribute to redox regulation. When their selenocysteine is replaced by cysteine, the cellular antioxidant defense system is impaired. Finally, classes of organoselenides have been synthesized with the aim of mimicking the biological strategy of glutathione peroxidases, but their therapeutic application has so far been limited. Moreover, their therapeutic use may be doubted, because H2O2 is not only toxic but also serves as an important messenger. Therefore, over-optimization of H2O2 reduction may lead to unexpected disturbances of metabolic regulation. Common to all these systems is the nucleophilic attack of selenium to one oxygen of the peroxide bond promoting its disruption. In this contribution, we revisit selected examples from chemistry and biology, and, by using results from accurate quantum mechanical modelling, we provide an accurate unified picture of selenium’s capacity of reducing hydroperoxides. There is clear evidence that the selenoenzymes remain superior in terms of catalytic efficiency.

Small-Molecule-Based Fluorescent Sensors for Selective Detection of Reactive Oxygen Species in Biological Systems

2019 ◽  
Vol 88 (1) ◽  
pp. 605-633 ◽  
Author(s):  
Xiaoyu Bai ◽  
Kenneth King-Hei Ng ◽  
Jun Jacob Hu ◽  
Sen Ye ◽  
Dan Yang
Keyword(s):  
Reactive Oxygen Species ◽  
Small Molecule ◽  
Redox Regulation ◽  
Biological Systems ◽  
Reactive Oxygen ◽  
Fluorescent Sensors ◽  
Ros Generation ◽  
Oxygen Species ◽  
Redox Biology ◽  
Health And Disease

Reactive oxygen species (ROS) encompass a collection of intricately linked chemical entities characterized by individually distinct physicochemical properties and biological reactivities. Although excessive ROS generation is well known to underpin disease development, it has become increasingly evident that ROS also play central roles in redox regulation and normal physiology. A major challenge in uncovering the relevant biological mechanisms and deconvoluting the apparently paradoxical roles of distinct ROS in human health and disease lies in the selective and sensitive detection of these transient species in the complex biological milieu. Small-molecule-based fluorescent sensors enable molecular imaging of ROS with great spatial and temporal resolution and have thus been appreciated as excellent tools for aiding discoveries in modern redox biology. We review a selection of state-of-the-art sensors with demonstrated utility in biological systems. By providing a systematic overview based on underlying chemical sensing mechanisms, we wish to highlight the strengths and weaknesses in prior sensor works and propose some guiding principles for the development of future probes.

scholarly journals Destroy and Exploit: Catalyzed Removal of Hydroperoxides from the Endoplasmic Reticulum

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas Ramming ◽  
Christian Appenzeller-Herzog
Keyword(s):  
Hydrogen Peroxide ◽  
Endoplasmic Reticulum ◽  
Second Messengers ◽  
Eukaryotic Cells ◽  
Lipid Hydroperoxides ◽  
Common Theme ◽  
Oxidative Protein Folding ◽  
Glutathione Peroxidases

Peroxidases are enzymes that reduce hydroperoxide substrates. In many cases, hydroperoxide reduction is coupled to the formation of a disulfide bond, which is transferred onto specific acceptor molecules, the so-called reducing substrates. As such, peroxidases control the spatiotemporal distribution of diffusible second messengers such as hydrogen peroxide (H2O2) and generate new disulfides. Members of two families of peroxidases, peroxiredoxins (Prxs) and glutathione peroxidases (GPxs), reside in different subcellular compartments or are secreted from cells. This review discusses the properties and physiological roles of PrxIV, GPx7, and GPx8 in the endoplasmic reticulum (ER) of higher eukaryotic cells where H2O2and—possibly—lipid hydroperoxides are regularly produced. Different peroxide sources and reducing substrates for ER peroxidases are critically evaluated. Peroxidase-catalyzed detoxification of hydroperoxides coupled to the productive use of disulfides, for instance, in the ER-associated process of oxidative protein folding, appears to emerge as a common theme. Nonetheless,in vitroandin vivostudies have demonstrated that individual peroxidases serve specific, nonoverlapping roles in ER physiology.

Signal-regulated oxidation of proteins via MICAL

2020 ◽  
Vol 48 (2) ◽  
pp. 613-620
Author(s):  
Clara Ortegón Salas ◽  
Katharina Schneider ◽  
Christopher Horst Lillig ◽  
Manuela Gellert
Keyword(s):  
Signal Transduction ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Redox Regulation ◽  
Signal Transduction Pathways ◽  
Cellular Functions ◽  
Intracellular Signals ◽  
Amino Acid Side Chains ◽  
Specific Receptors ◽  
Sulfur Containing

Processing of and responding to various signals is an essential cellular function that influences survival, homeostasis, development, and cell death. Extra- or intracellular signals are perceived via specific receptors and transduced in a particular signalling pathway that results in a precise response. Reversible post-translational redox modifications of cysteinyl and methionyl residues have been characterised in countless signal transduction pathways. Due to the low reactivity of most sulfur-containing amino acid side chains with hydrogen peroxide, for instance, and also to ensure specificity, redox signalling requires catalysis, just like phosphorylation signalling requires kinases and phosphatases. While reducing enzymes of both cysteinyl- and methionyl-derivates have been characterised in great detail before, the discovery and characterisation of MICAL proteins evinced the first examples of specific oxidases in signal transduction. This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions.

scholarly journals Detection of metal ions in biological systems: A review

2020 ◽  
Vol 39 (1) ◽  
pp. 231-246 ◽  
Author(s):  
Xian Zheng ◽  
Wenyu Cheng ◽  
Chendong Ji ◽  
Jin Zhang ◽  
Meizhen Yin
Keyword(s):  
Metal Ions ◽  
Metal Ion ◽  
Metabolic Regulation ◽  
Organic Dyes ◽  
Biological Systems ◽  
High Sensitivity ◽  
Transportation Energy ◽  
Material Transportation ◽  
High Fluorescence ◽  
Metal Ion Detection

Abstract Metal ions are widely present in biological systems and participate in many critical biochemical processes such as material transportation, energy conversion, information transmission and metabolic regulation, making them indispensable substance in our body. They can cause health problems when deficiency or excess occurs. To understand various metabolic processes and facilitate diseases diagnosis, it is very important to measure the content and monitor the distribution of metal ions in individual cells, tissues and whole organisms. Among the various methods for metal ion detection, fluorescent sensors with organic dyes have attracted tremendous attention due to many advantages such as high fluorescence quantum yield, facile modification approaches and biocompatibility in addition to operation ease, high sensitivity, fast detection speed, and real-time detection. This review summarizes the recent progress on the detection and imaging of the metal ions in biological systems including Na+, K+, Ca2+, Mg2+, Fe2+/Fe3+, Zn2+, and Cu2+ provides an opinion on remaining challenges to be addressed in this field.

scholarly journals Embryonic Origin and Subclonal Evolution of Tumor-Associated Macrophages Imply Preventive Care for Cancer

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 903
Author(s):  
Xiao-Mei Zhang ◽  
De-Gao Chen ◽  
Shengwen Calvin Li ◽  
Bo Zhu ◽  
Zhong-Jun Li
Keyword(s):  
Metabolic Regulation ◽  
Transcriptional Profiling ◽  
Tumor Development ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Functional Heterogeneity ◽  
Tumor Associated Macrophages ◽  
Metabolic Remodeling ◽  
And Function ◽  
Mapping Models

Macrophages are widely distributed in tissues and function in homeostasis. During cancer development, tumor-associated macrophages (TAMs) dominatingly support disease progression and resistance to therapy by promoting tumor proliferation, angiogenesis, metastasis, and immunosuppression, thereby making TAMs a target for tumor immunotherapy. Here, we started with evidence that TAMs are highly plastic and heterogeneous in phenotype and function in response to microenvironmental cues. We pointed out that efforts to tear off the heterogeneous “camouflage” in TAMs conduce to target de facto protumoral TAMs efficiently. In particular, several fate-mapping models suggest that most tissue-resident macrophages (TRMs) are generated from embryonic progenitors, and new paradigms uncover the ontogeny of TAMs. First, TAMs from embryonic modeling of TRMs and circulating monocytes have distinct transcriptional profiling and function, suggesting that the ontogeny of TAMs is responsible for the functional heterogeneity of TAMs, in addition to microenvironmental cues. Second, metabolic remodeling helps determine the mechanism of phenotypic and functional characteristics in TAMs, including metabolic bias from macrophages’ ontogeny in macrophages’ functional plasticity under physiological and pathological conditions. Both models aim at dissecting the ontogeny-related metabolic regulation in the phenotypic and functional heterogeneity in TAMs. We argue that gleaning from the single-cell transcriptomics on subclonal TAMs’ origins may help understand the classification of TAMs’ population in subclonal evolution and their distinct roles in tumor development. We envision that TAM-subclone-specific metabolic reprogramming may round-up with future cancer therapies.

scholarly journals Cloning, Expression, and Purification of a Nitric Oxide Synthase-Like Protein fromBacillus cereus

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Heather J. Montgomery ◽  
Andrea L. Dupont ◽  
Hilary E. Leivo ◽  
J. Guy Guillemette
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Nitric Oxide Synthase ◽  
Expression And Purification ◽  
Spectral Shifts ◽  
Reconstituted System ◽  
Low Levels ◽  
And Function ◽  
Oxide Synthase ◽  
Reductase Domain

The nitric oxide synthase-like protein fromBacillus cereus(bcNOS) has been cloned, expressed, and characterized. This small hemeprotein (356 amino acids in length) has a mass of 43 kDa and forms a dimer. The recombinant protein showed similar spectral shifts to the mammalian NOS proteins and could bind the substrates L-arginine andNG-hydroxy-L-arginine as well as the ligand imidazole. Low levels of activity were recorded for the hydrogen peroxide-dependent oxidation ofNG-hydroxy-L-arginine and L-arginine by bcNOS, while a reconstituted system with the rat neuronal NOS reductase domain showed no activity. The recombinant bcNOS protein adds to the complement of bacterial NOS-like proteins that are used for the investigation of the mechanism and function of NO in microorganisms.

Repeat proteins challenge the concept of structural domains

2015 ◽  
Vol 43 (5) ◽  
pp. 844-849 ◽  
Author(s):  
Rocío Espada ◽  
R. Gonzalo Parra ◽  
Manfred J. Sippl ◽  
Thierry Mora ◽  
Aleksandra M. Walczak ◽  
...  
Keyword(s):  
Biological Systems ◽  
Modular Structure ◽  
Structural Domains ◽  
Repeat Array ◽  
Repeat Units ◽  
Repeat Proteins ◽  
Folding Dynamics ◽  
And Function

Structural domains are believed to be modules within proteins that can fold and function independently. Some proteins show tandem repetitions of apparent modular structure that do not fold independently, but rather co-operate in stabilizing structural forms that comprise several repeat-units. For many natural repeat-proteins, it has been shown that weak energetic links between repeats lead to the breakdown of co-operativity and the appearance of folding sub-domains within an apparently regular repeat array. The quasi-1D architecture of repeat-proteins is crucial in detailing how the local energetic balances can modulate the folding dynamics of these proteins, which can be related to the physiological behaviour of these ubiquitous biological systems.

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