Redox-Regulation of α-Globin in Vascular Physiology

Interest in the structure, function, and evolutionary relations of circulating and intracellular globins dates back more than 60 years to the first determination of the three-dimensional structure of these proteins. Non-erythrocytic globins have been implicated in circulatory control through reactions that couple nitric oxide (NO) signaling with cellular oxygen availability and redox status. Small artery endothelial cells (ECs) express free α-globin, which causes vasoconstriction by degrading NO. This reaction converts reduced (Fe2+) α-globin to the oxidized (Fe3+) form, which is unstable, cytotoxic, and unable to degrade NO. Therefore, (Fe3+) α-globin must be stabilized and recycled to (Fe2+) α-globin to reinitiate the catalytic cycle. The molecular chaperone α-hemoglobin-stabilizing protein (AHSP) binds (Fe3+) α-globin to inhibit its degradation and facilitate its reduction. The mechanisms that reduce (Fe3+) α-globin in ECs are unknown, although endothelial nitric oxide synthase (eNOS) and cytochrome b5 reductase (CyB5R3) with cytochrome b5 type A (CyB5a) can reduce (Fe3+) α-globin in solution. Here, we examine the expression and cellular localization of eNOS, CyB5a, and CyB5R3 in mouse arterial ECs and show that α-globin can be reduced by either of two independent redox systems, CyB5R3/CyB5a and eNOS. Together, our findings provide new insights into the regulation of blood vessel contractility.

Cultivation of Cells in a Physiological Plasmax Medium Increases Mitochondrial Respiratory Capacity and Reduces Replication Levels of RNA Viruses

Changes in metabolic pathways are often associated with the development of various pathologies including cancer, inflammatory diseases, obesity and metabolic syndrome. Identification of the particular metabolic events that are dysregulated may yield strategies for pharmacologic intervention. However, such studies are hampered by the use of classic cell media that do not reflect the metabolite composition that exists in blood plasma and which cause non-physiological adaptations in cultured cells. In recent years two groups presented media that aim to reflect the composition of human plasma, namely human plasma-like medium (HPLM) and Plasmax. Here we describe that, in four different mammalian cell lines, Plasmax enhances mitochondrial respiration. This is associated with the formation of vast mitochondrial networks and enhanced production of reactive oxygen species (ROS). Interestingly, cells cultivated in Plasmax displayed significantly less lysosomes than when any standard media were used. Finally, cells cultivated in Plasmax support replication of various RNA viruses, such as hepatitis C virus (HCV) influenza A virus (IAV), severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and several others, albeit at lower levels and with delayed kinetics. In conclusion, studies of metabolism in the context of viral infections, especially those concerning mitochondria, lysosomes, or redox systems, should be performed in Plasmax medium.

Understanding Cellular Redox Homeostasis: A Challenge for Precision Medicine

Living organisms use a large repertoire of anabolic and catabolic reactions to maintain their physiological body functions, many of which include oxidation and reduction of substrates. The scientific field of redox biology tries to understand how redox homeostasis is regulated and maintained and which mechanisms are derailed in diverse pathological developments of diseases, where oxidative or reductive stress is an issue. The term “oxidative stress” is defined as an imbalance between the generation of oxidants and the local antioxidative defense. Key mediators of oxidative stress are reactive species derived from oxygen, nitrogen, and sulfur that are signal factors at physiological concentrations but can damage cellular macromolecules when they accumulate. However, therapeutical targeting of oxidative stress in disease has proven more difficult than previously expected. Major reasons for this are the very delicate cellular redox systems that differ in the subcellular compartments with regard to their concentrations and depending on the physiological or pathological status of cells and organelles (i.e., circadian rhythm, cell cycle, metabolic need, disease stadium). As reactive species are used as signaling molecules, non-targeted broad-spectrum antioxidants in many cases will fail their therapeutic aim. Precision medicine is called to remedy the situation.

Electrochemical properties of quinones, antraquinones and their derivatives – potential redox-systems for flow batteries

Practical interest in redox flow batteries has arisen in recent decades as a result of intensive development in the field of alternative energy (such as solar and wind) and the control of peak loads in industrial electrical networks. It turned out that large-scale energy storage systems used to compensate fluctuations in the process of solar and wind generation of energy in the production of electric vehicles and power supply systems for large households, are more profitable when working on redox flow batteries. Firstly, they are easy to scale, and secondly, the energy stored in such batteries is cheaper. In recent years, the interest of researchers in the redox behavior of simple and substituted quinones and anthraquinones used as potential components of electrochemical energy storage systems has grown significantly. The main advantages of organic redox systems are scalability, kinetic advantages over the used redox systems based on inorganic substances, reconstructability (a wide possibility of changing electrochemical and chemical properties by introducing various functional groups into organic molecules) and environmental safety. Therefore, in this work, the electrochemical behavior of some promising organic systems based on quinone, anthraquinone and their analogs to be used as redox systems of flow batteries was studied using the method of cyclic voltammetry.

Redox Systems, Oxidative Stress, and Antioxidant Defences in Health and Disease

Reactive oxygen and nitrogen species (RONS) play a key role in the regulation of cell survival [...]

Physicochemical and Analytical Implications of GATES/GEB Principles

The fundamental property of electrolytic systems involved with linear combination f12 = 2∙f(O) – f(H) of elemental balances: f1 = f(H) for Y1 = H, and f2 = f(O) for Y2 = O, is presented. The dependency/independency of the f12 on Charge Balance (f0 = ChB) and other elemental and/or core balances fk = f(Yk) (k = 3,…,K) is the general criterion distinguishing between non-redox and redox systems. The f12 related to a redox system is the primary form of a Generalized Electron Balance (GEB), formulated for redox systems within the Generalized Approach to Electrolytic System (GATES) as GATES/GEB ⊂ GATES. The set of K balances f0,f12,f3,…,fK is necessary/ sufficient/needed to solve an electrolytic redox system, while the K-1 balances f0,f3,…,fK are the set applied to solve an electrolytic non-redox system. The identity (0 = 0) procedure of checking the linear independency/ dependency property of f12 within the set f0,f12,f3,…,fK (i) provides the criterion distinguishing between the redox and non-redox systems and (ii) specifies Oxidation Numbers (ONs) of elements in particular components of the system, and in the species formed in the system. Some chemical concepts, such as oxidant, reductant, oxidation number, equivalent mass, stoichiometry, perceived as derivative within GATES, are indicated. All the information is gained on the basis of the titration Ce(SO4)2 (C) + H2SO4 (C1) + CO2 (C2) ⇨ FeSO4 (C0) + H2SO4 (C01) + CO2 (C02), simulated with use of the iterative computer program MATLAB.

REDOX PROCESSES IN THE REACTIONS OF N-ARYLSULFONYL-1,4-NAPHTНOQUINONЕIMINES WITH CERTAIN NUCLEOPHILES

Quinone-hydroquinone pairs are prototypes of organic redox systems, and studies of the electrochemical behavior of these compounds are of great interest for research. Electrochemical behavior associated with the equilibrium of electron-proton transfer provides information about the molecular structure and environment of the process. Apart from chemical aspects, quinones play an important role in the biochemistry of living cells. Quinone derivatives, used as drugs for several types of human cancers, have been found to have their biological activity related to their redox behavior. Quinoneimines-aminophenols form similar pairs. In nucleophilic addition reactions of N‑substituted p-quinoneimines, parallel redox processes are often observed, and the higher the redox potential of quinoneimine, the greater the likelihood of such processes. Naphthoquinoneimines with aromatic amines and acylhydrazines follow the scheme of 1,4-addition, but as reaction products are oxidized products -4-arylsulfonylamido‑2-arylamino(2-aroylamino)-1,4-naphthoquinoneimines. The oxidant may be the original naphthoquinoneimine and oxygen. Studies have shown that oxygen in the reaction of 1,4-naphthoquinoneimines with acylhydrazines is the only oxidant that oxidizes the product of 1,4-addition, as evidenced by the study of redox potentials. Both oxidized and reduced form of the compounds, as naphthoquinoneimine and the corresponding aminonaphthol, are used to determine the redox potential by direct potentiometry. Due to the instability of the reduced form in the case of the pair naphthoquinoneimine-aminonaphthol, we used only the reduced form, which is oxidized in the cell by oxygen. The redox potential of the naphthoquinoneimine-aminonaphthol galvanic pair was determined as the average value between the potential Emax, which was established in the system upon complete oxidation of the starting substance, that is, when only naphthoquinone imine remains in the system, and the potential Emin, which was registered at the beginning of the process in the system with the reduced form – the corresponding aminonaphthol. This is the method of direct potentiometry in the variant of the middle potential.

A Regulatory Network of Heat Shock Modules-Photosynthesis-Redox Systems in Response to Cold Stress Across a Latitudinal Gradient in Bermudagrass

Bermudagrass (Cynodon dactylon Pers.) is a wild Poaceae turfgrass with various genotypes and phenotypes. In this study, 16 wild bermudagrass germplasms were collected from 16 different sites along latitudinal gradients, and different temperature treatments were compiled and used for physiological and transcriptome analysis. To explore the correlation between the key differentially expressed genes and physiological indicators, a total of 14,654 DEGs were integrated from the comparison of different temperature treatments and used for weighted gene co-expression network analysis. Through comparative transcriptome analysis and gene annotation, the results showed that differential gene expression profiles in networks are associated with the plant growth, photosystem, redox system, and transcriptional regulation to cold stress in bermudagrass. In particular, genes encoding HSP70/90 and HsfA3/A8 are not only regulated by temperature stress, but also directly or indirectly interplay with the processes of peroxide scavenging and chlorophyll synthesis under cold stress. Besides, through a weight evaluation analysis of various physiological indexes, we identified an accession of wild bermudagrass with relatively strong cold resistance. These results provide important clues and resources to further study the responses to low-temperature stress in bermudagrass.