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1.
Reactive oxygen species as mediators of oxygen signaling during fetal-to-neonatal circulatory transition.
Villamor, E, Moreno, L, Mohammed, R, Pérez-Vizcaíno, F, Cogolludo, A
Free radical biology & medicine. 2019;:82-96
Abstract
Reactive oxygen species (ROS) are frequently seen as pathological agents of oxidative stress. However, ROS are not always deleterious and can also act as cell signaling molecules. Vascular oxygen sensing and signaling during fetal-to-neonatal circulatory transition is a remarkable example of the physiological regulatory actions of ROS. The fetal relative hypoxic environment induces hypoxic pulmonary vasoconstriction (HPV) and ductus arteriosus (DA) relaxation favoring the presence of high pulmonary vascular resistance and right-to-left ductal shunt. At birth, the increase in oxygen tension causes relaxation of pulmonary arteries (PAs) and normoxic DA vasoconstriction (NDAV), thus diverting blood flow to the lungs. Although the response to changes in oxygen tension is diametrically opposite, the mechanisms responsible for HPV and NDAV appear to be the result of a similar interaction between triggering and modulating factors that lead to an increase in cytosolic Ca2+ concentration and Ca2+ sensitization of the contractile apparatus. Growing evidence points to an increase in ROS (mitochondria- and/or NADPH-derived superoxide and/or H2O2), leading to inhibition of voltage-gated K+ channels, membrane depolarization, and activation of voltage-gated L-type Ca2+ channels as critical events in the signaling pathway of both HPV and NDAV. Several groups of investigators have completed this pathway adding other elements such as neutral sphingomyelinase-derived ceramide, the sarcoplasmic/endoplasmic reticulum (through ryanodine and inositol 1,4,5-trisphosphate receptors), Rho kinase-mediated Ca2+ sensitization, or transient receptor potential channels. The present review focus on the role of ROS as mediators of the homeostatic oxygen sensing system during fetal and neonatal life not only in the PAs and DA but also in systemic arteries.
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2.
Cyanobacteria evolution: Insight from the fossil record.
Demoulin, CF, Lara, YJ, Cornet, L, François, C, Baurain, D, Wilmotte, A, Javaux, EJ
Free radical biology & medicine. 2019;:206-223
Abstract
Cyanobacteria played an important role in the evolution of Early Earth and the biosphere. They are responsible for the oxygenation of the atmosphere and oceans since the Great Oxidation Event around 2.4 Ga, debatably earlier. They are also major primary producers in past and present oceans, and the ancestors of the chloroplast. Nevertheless, the identification of cyanobacteria in the early fossil record remains ambiguous because the morphological criteria commonly used are not always reliable for microfossil interpretation. Recently, new biosignatures specific to cyanobacteria were proposed. Here, we review the classic and new cyanobacterial biosignatures. We also assess the reliability of the previously described cyanobacteria fossil record and the challenges of molecular approaches on modern cyanobacteria. Finally, we suggest possible new calibration points for molecular clocks, and strategies to improve our understanding of the timing and pattern of the evolution of cyanobacteria and oxygenic photosynthesis.
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Mechanisms of toxicity by and resistance to ferrous iron in anaerobic systems.
Bennett, BD, Gralnick, JA
Free radical biology & medicine. 2019;:167-171
Abstract
Iron is an essential element for nearly all life on Earth, primarily for its value as a redox active cofactor. Iron exists predominantly in two biologically relevant redox states: ferric iron, the oxidized state (Fe3+), and ferrous iron, the reduced state (Fe2+). Fe2+ is well known to facilitate electron transfer reactions that can lead to the generation of reactive oxygen species. Less is known about why iron is toxic to cells in the absence of oxygen, yet this phenomenon is critically important for our understanding of life on early Earth and in iron-rich ecosystems today. In this brief review, we will highlight our current understanding of anaerobic Fe2+ toxicity, focusing on molecular mechanistic studies in several model systems.
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4.
Oxygen Saturation and Retinopathy of Prematurity.
Higgins, RD
Clinics in perinatology. 2019;(3):593-599
Abstract
Retinopathy of prematurity (ROP) is a serious disease affecting premature infants. Rates of ROP increase with decreasing gestational age. Duration of oxygen exposure is correlated with ROP. Many studies evaluating oxygen have been performed to assess impact on ROP. This article describes recent findings for oxygen saturation target studies and suggests area of future study for ROP.
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Tolerance of roots to low oxygen: 'Anoxic' cores, the phytoglobin-nitric oxide cycle, and energy or oxygen sensing.
Armstrong, W, Beckett, PM, Colmer, TD, Setter, TL, Greenway, H
Journal of plant physiology. 2019;:92-108
Abstract
Acclimation by plants to hypoxia and anoxia is of importance in various ecological systems, and especially for roots in waterlogged soil. We present evidence for acclimation by roots via 'anoxic' cores rather than being triggered by O2 sensors. The evidence for 'anoxic' cores comes from radial O2 profiles across maize roots and associated metabolic changes such as increases in the 'anaerobic enzymes' ADH and PDC in the 'anoxic' core, and inhibition of Cl- transport to the xylem. These cores are predicted to develop within 15-20 min after sudden transfer of a root to hypoxia, so that the cores are 'anoxically-shocked'. We suggest that 'anoxic' cores could emanate a signal(s), such as ACC the precursor of ethylene and/or propagation of a 'Ca2+ wave', to other tissue zones. There, the signalling would result in acclimation of the tissues to energy crisis metabolism. An O2 diffusion model for tissues with an 'anoxic' core, indicates that the phytoglobin-nitric oxide (Pgb-NO) cycle would only be engaged in a thin 'shell' (annulus) of tissue surrounding the 'anoxic' core, and so would only contribute small amounts of ATP on a whole organ basis (e.g. whole roots). A key feature within this annulus of tissue, where O2 is likely to be limiting, is that the ratio (ATP formed) / (O2 consumed) is 5-6, both when the NAD(P)H of glycolysis is converted to NAD(P)+ by the Pgb-NO cycle or by the TCA cycle linked to the electron transport chain. The main function of the Pgb-NO cycle may be the modulating of NO levels and O2 scavenging, thus preventing oxidative damage. We speculate that an 'anoxic' core in hypoxic plant organs may have a particularly high tolerance to anoxia because cells might receive a prolonged supply of carbohydrates and/or ATP from the regions still receiving sufficient O2 for oxidative phosphorylation. Severely hypoxic or 'anoxic' cores are well documented, but much research on responses of roots to hypoxia is still based on bulk tissue analyses. More research is needed on the interaction between 'anoxic' cores and tissues still receiving sufficient O2 for oxidative phosphorylation, both during a hypoxic exposure and during subsequent anoxia of the tissue/organ as a whole.
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6.
Role and regulation of class-C flavodiiron proteins in photosynthetic organisms.
Alboresi, A, Storti, M, Cendron, L, Morosinotto, T
The Biochemical journal. 2019;(17):2487-2498
Abstract
The regulation of photosynthesis is crucial to efficiently support the assimilation of carbon dioxide and to prevent photodamage. One key regulatory mechanism is the pseudo-cyclic electron flow (PCEF) mediated by class-C flavodiiron proteins (FLVs). These enzymes use electrons coming from Photosystem I (PSI) to reduce oxygen to water, preventing over-reduction in the acceptor side of PSI. FLVs are widely distributed among organisms performing oxygenic photosynthesis and they have been shown to be fundamental in many different conditions such as fluctuating light, sulfur deprivation and plant submersion. Moreover, since FLVs reduce oxygen they can help controlling the redox status of the cell and maintaining the microoxic environment essential for processes such as nitrogen fixation in cyanobacteria. Despite these important roles identified in various species, the genes encoding for FLV proteins have been lost in angiosperms where their activity could have been at least partially compensated by a more efficient cyclic electron flow (CEF). The present work reviews the information emerged on FLV function, analyzing recent structural data that suggest FLV could be regulated through a conformational change.
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7.
Artificial Oxygen Carriers-Past, Present, and Future-a Review of the Most Innovative and Clinically Relevant Concepts.
Ferenz, KB, Steinbicker, AU
The Journal of pharmacology and experimental therapeutics. 2019;(2):300-310
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Abstract
Blood transfusions are a daily practice in hospitals. Since these products are limited in availability and have various, harmful side effects, researchers have pursued the goal to develop artificial blood components for about 40 years. Development of oxygen therapeutics and stem cells are more recent goals. Medline (https://www.ncbi.nlm.nih.gov/pubmed/?holding=ideudelib), ClinicalTrials.gov (https://clinicaltrials.gov), EU Clinical Trials Register (https://www.clinicaltrialsregister.eu), and Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au) were searched up to July 2018 using search terms related to artificial blood products in order to identify new and ongoing research over the last 5 years. However, for products that are already well known and important to or relevant in gaining a better understanding of this field of research, the reader is punctually referred to some important articles published over 5 years ago. This review includes not only clinically relevant substances such as heme-oxygenating carriers, perfluorocarbon-based oxygen carriers, stem cells, and organ conservation, but also includes interesting preclinically advanced compounds depicting the pipeline of potential new products. In- depth insights into specific benefits and limitations of each substance, including the biochemical and physiologic background are included. "Fancy" ideas such as iron-based substances, O2 microbubbles, cyclodextranes, or lugworms are also elucidated. To conclude, this systematic up-to-date review includes all actual achievements and ongoing clinical trials in the field of artificial blood products to pursue the dream of artificial oxygen carrier supply. Research is on the right track, but the task is demanding and challenging.
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8.
Water oxidation in photosystem II.
Lubitz, W, Chrysina, M, Cox, N
Photosynthesis research. 2019;(1):105-125
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Abstract
Biological water oxidation, performed by a single enzyme, photosystem II, is a central research topic not only in understanding the photosynthetic apparatus but also for the development of water splitting catalysts for technological applications. Great progress has been made in this endeavor following the report of a high-resolution X-ray crystallographic structure in 2011 resolving the cofactor site (Umena et al. in Nature 473:55-60, 2011), a tetra-manganese calcium complex. The electronic properties of the protein-bound water oxidizing Mn4OxCa complex are crucial to understand its catalytic activity. These properties include: its redox state(s) which are tuned by the protein matrix, the distribution of the manganese valence and spin states and the complex interactions that exist between the four manganese ions. In this short review we describe how magnetic resonance techniques, particularly EPR, complemented by quantum chemical calculations, have played an important role in understanding the electronic structure of the cofactor. Together with isotope labeling, these techniques have also been instrumental in deciphering the binding of the two substrate water molecules to the cluster. These results are briefly described in the context of the history of biological water oxidation with special emphasis on recent work using time resolved X-ray diffraction with free electron lasers. It is shown that these data are instrumental for developing a model of the biological water oxidation cycle.
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Energy metabolism in anaerobic eukaryotes and Earth's late oxygenation.
Zimorski, V, Mentel, M, Tielens, AGM, Martin, WF
Free radical biology & medicine. 2019;:279-294
Abstract
Eukaryotes arose about 1.6 billion years ago, at a time when oxygen levels were still very low on Earth, both in the atmosphere and in the ocean. According to newer geochemical data, oxygen rose to approximately its present atmospheric levels very late in evolution, perhaps as late as the origin of land plants (only about 450 million years ago). It is therefore natural that many lineages of eukaryotes harbor, and use, enzymes for oxygen-independent energy metabolism. This paper provides a concise overview of anaerobic energy metabolism in eukaryotes with a focus on anaerobic energy metabolism in mitochondria. We also address the widespread assumption that oxygen improves the overall energetic state of a cell. While it is true that ATP yield from glucose or amino acids is increased in the presence of oxygen, it is also true that the synthesis of biomass costs thirteen times more energy per cell in the presence of oxygen than in anoxic conditions. This is because in the reaction of cellular biomass with O2, the equilibrium lies very far on the side of CO2. The absence of oxygen offers energetic benefits of the same magnitude as the presence of oxygen. Anaerobic and low oxygen environments are ancient. During evolution, some eukaryotes have specialized to life in permanently oxic environments (life on land), other eukaryotes have remained specialized to low oxygen habitats. We suggest that the Km of mitochondrial cytochrome c oxidase of 0.1-10 μM for O2, which corresponds to about 0.04%-4% (avg. 0.4%) of present atmospheric O2 levels, reflects environmental O2 concentrations that existed at the time that the eukaryotes arose.
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Retinal oximetry: Metabolic imaging for diseases of the retina and brain.
Stefánsson, E, Olafsdottir, OB, Eliasdottir, TS, Vehmeijer, W, Einarsdottir, AB, Bek, T, Torp, TL, Grauslund, J, Eysteinsson, T, Karlsson, RA, et al
Progress in retinal and eye research. 2019;:1-22
Abstract
Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment. Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular edema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia. Glaucomatous retinal atrophy is associated with reduced oxygen consumption resulting in reduced arteriovenous difference and higher retinal venous saturation. The oximetry findings correlate with worse visual field, thinner nerve fiber layer and smaller optic disc rim. This provides an objective biomarker for glaucomatous damage. In retinitis pigmentosa, an association exists between advanced atrophy, worse visual field and higher retinal venous oxygen saturation, lower arteriovenous difference. This biomarker may allow measurement of severity and progression of retinitis pigmentosa and other atrophic retinal diseases. Retinal oximetry offers visible light imaging of systemic and central nervous system vessels. It senses hypoxia in cardiac and pulmonary diseases. Oximetry biomarkers have been discovered in Alzheimer's disease and multiple sclerosis and oxygen levels in the retina correspond well with brain.