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International Journal of Molecular... Sep 2015Magnesium (Mg) is the second most abundant cation in living cells. Over 300 enzymes are known to be Mg-dependent, and changes in the Mg concentration significantly... (Review)
Review
Magnesium (Mg) is the second most abundant cation in living cells. Over 300 enzymes are known to be Mg-dependent, and changes in the Mg concentration significantly affects the membrane potential. As Mg becomes deficient, starch accumulation and chlorosis, bridged by the generation of reactive oxygen species, are commonly found in Mg-deficient young mature leaves. These defects further cause the inhibition of photosynthesis and finally decrease the biomass. Recently, transcriptome analysis has indicated the transcriptinal downregulation of chlorophyll apparatus at the earlier stages of Mg deficiency, and also the potential involvement of complicated networks relating to hormonal signaling and circadian oscillation. However, the processes of the common symptoms as well as the networks between Mg deficiency and signaling are not yet fully understood. Here, for the purpose of defining the missing pieces, several problems are considered and explained by providing an introduction to recent reports on physiological and transcriptional responses to Mg deficiency. In addition, it has long been unclear whether the Mg deficiency response involves the modulation of Mg2+ transport system. In this review, the current status of research on Mg2+ transport and the relating transporters are also summarized. Especially, the rapid progress in physiological characterization of the plant MRS2 gene family as well as the fundamental investigation about the molecular mechanism of the action of bacterial CorA proteins are described.
Topics: Biological Transport; Cation Transport Proteins; Cations, Divalent; Gene Expression Regulation, Plant; Magnesium; Plant Leaves; Plant Proteins; Plants
PubMed: 26404266
DOI: 10.3390/ijms160923076 -
PloS One 2014Stirred-suspension bioreactors are a promising modality for large-scale culture of 3D aggregates of pluripotent stem cells and their progeny. Yet, cells within these...
Stirred-suspension bioreactors are a promising modality for large-scale culture of 3D aggregates of pluripotent stem cells and their progeny. Yet, cells within these clusters experience limitations in the transfer of factors and particularly O2 which is characterized by low solubility in aqueous media. Cultured stem cells under different O2 levels may exhibit significantly different proliferation, viability and differentiation potential. Here, a transient diffusion-reaction model was built encompassing the size distribution and ultrastructural characteristics of embryonic stem cell (ESC) aggregates. The model was coupled to experimental data from bioreactor and static cultures for extracting the effective diffusivity and kinetics of consumption of O2 within mouse (mESC) and human ESC (hESC) clusters. Under agitation, mESC aggregates exhibited a higher maximum consumption rate than hESC aggregates. Moreover, the reaction-diffusion model was integrated with a population balance equation (PBE) for the temporal distribution of ESC clusters changing due to aggregation and cell proliferation. Hypoxia was found to be negligible for ESCs with a smaller radius than 100 µm but became appreciable for aggregates larger than 300 µm. The integrated model not only captured the O2 profile both in the bioreactor bulk and inside ESC aggregates but also led to the calculation of the duration that fractions of cells experience a certain range of O2 concentrations. The approach described in this study can be employed for gaining a deeper understanding of the effects of O2 on the physiology of stem cells organized in 3D structures. Such frameworks can be extended to encompass the spatial and temporal availability of nutrients and differentiation factors and facilitate the design and control of relevant bioprocesses for the production of stem cell therapeutics.
Topics: Animals; Biological Transport; Bioreactors; Cell Aggregation; Cell Culture Techniques; Cell Hypoxia; Cell Proliferation; Cells, Cultured; Human Embryonic Stem Cells; Humans; Mice; Mouse Embryonic Stem Cells; Oxygen; Oxygen Consumption
PubMed: 25032842
DOI: 10.1371/journal.pone.0102486 -
Advances in Experimental Medicine and... 2016The 'Pathway for Oxygen' is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external...
The 'Pathway for Oxygen' is captured in a set of models describing quantitative relationships between fluxes and driving forces for the flux of oxygen from the external air source to the mitochondrial sink at cytochrome oxidase. The intervening processes involve convection, membrane permeation, diffusion of free and heme-bound O2 and enzymatic reactions. While this system's basic elements are simple: ventilation, alveolar gas exchange with blood, circulation of the blood, perfusion of an organ, uptake by tissue, and consumption by chemical reaction, integration of these pieces quickly becomes complex. This complexity led us to construct a tutorial on the ideas and principles; these first PathwayO2 models are simple but quantitative and cover: (1) a 'one-alveolus lung' with airway resistance, lung volume compliance, (2) bidirectional transport of solute gasses like O2 and CO2, (3) gas exchange between alveolar air and lung capillary blood, (4) gas solubility in blood, and circulation of blood through the capillary syncytium and back to the lung, and (5) blood-tissue gas exchange in capillaries. These open-source models are at Physiome.org and provide background for the many respiratory models there.
Topics: Biological Transport; Humans; Lung; Mitochondria; Models, Biological; Oxygen
PubMed: 26782201
DOI: 10.1007/978-1-4939-3023-4_13 -
International Journal of Molecular... Mar 2016Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits... (Review)
Review
Resveratrol (3,4',5-trihydroxy-trans-stilbene, RSV) has emerged as an important molecule in the biomedical area. This is due to its antioxidant and health benefits exerted in mammals. Nonetheless, early studies have also demonstrated its toxic properties toward plant-pathogenic fungi of this phytochemical. Both effects appear to be opposed and caused by different molecular mechanisms. However, the inhibition of cellular respiration is a hypothesis that might explain both toxic and beneficial properties of resveratrol, since this phytochemical: (1) decreases the production of energy of plant-pathogenic organisms, which prevents their proliferation; (2) increases adenosine monophosphate/adenosine diphosphate (AMP/ADP) ratio that can lead to AMP protein kinase (AMPK) activation, which is related to its health effects, and (3) increases the reactive oxygen species generation by the inhibition of electron transport. This pro-oxidant effect induces expression of antioxidant enzymes as a mechanism to counteract oxidative stress. In this review, evidence is discussed that supports the hypothesis that cellular respiration is the main target of resveratrol.
Topics: Animals; Antioxidants; Cell Respiration; Humans; Oxidative Stress; Resveratrol; Stilbenes
PubMed: 26999118
DOI: 10.3390/ijms17030368 -
International Journal of Molecular... Dec 2020In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in...
In eukaryotic algae, respiratory O uptake is enhanced after illumination, which is called light-enhanced respiration (LER). It is likely stimulated by an increase in respiratory substrates produced during photosynthetic CO assimilation and function in keeping the metabolic and redox homeostasis in the light in eukaryotic cells, based on the interactions among the cytosol, chloroplasts, and mitochondria. Here, we first characterize LER in photosynthetic prokaryote cyanobacteria, in which respiration and photosynthesis share their metabolisms and electron transport chains in one cell. From the physiological analysis, the cyanobacterium sp. PCC 6803 performs LER, similar to eukaryotic algae, which shows a capacity comparable to the net photosynthetic O evolution rate. Although the respiratory and photosynthetic electron transports share the interchain, LER was uncoupled from photosynthetic electron transport. Mutant analyses demonstrated that LER is motivated by the substrates directly provided by photosynthetic CO assimilation, but not by glycogen. Further, the light-dependent activation of LER was observed even with exogenously added glucose, implying a regulatory mechanism for LER in addition to the substrate amounts. Finally, we discuss the physiological significance of the large capacity of LER in cyanobacteria and eukaryotic algae compared to those in plants that normally show less LER.
Topics: Cell Respiration; Cyanobacteria; Electron Transport; Light; Oxidation-Reduction; Oxygen; Photosynthesis
PubMed: 33396191
DOI: 10.3390/ijms22010342 -
International Journal of Molecular... Feb 2022Changes in bacterial physiology caused by the combined action of the magnetic force and microgravity were studied in grown using a specially developed device aboard the... (Comparative Study)
Comparative Study
Changes in bacterial physiology caused by the combined action of the magnetic force and microgravity were studied in grown using a specially developed device aboard the International Space Station. The morphology and metabolism of grown under spaceflight (SF) or combined spaceflight and magnetic force (SF + MF) conditions were compared with ground cultivated bacteria grown under standard (control) or magnetic force (MF) conditions. SF, SF + MF, and MF conditions provided the up-regulation of Ag43 auto-transporter and cell auto-aggregation. The magnetic force caused visible clustering of non-sedimenting bacteria that formed matrix-containing aggregates under SF + MF and MF conditions. Cell auto-aggregation was accompanied by up-regulation of glyoxylate shunt enzymes and Vitamin B12 transporter BtuB. Under SF and SF + MF but not MF conditions nutrition and oxygen limitations were manifested by the down-regulation of glycolysis and TCA enzymes and the up-regulation of methylglyoxal bypass. Bacteria grown under combined SF + MF conditions demonstrated superior up-regulation of enzymes of the methylglyoxal bypass and down-regulation of glycolysis and TCA enzymes compared to SF conditions, suggesting that the magnetic force strengthened the effects of microgravity on the bacterial metabolism. This strengthening appeared to be due to magnetic force-dependent bacterial clustering within a small volume that reinforced the effects of the microgravity-driven absence of convectional flows.
Topics: Bacterial Outer Membrane Proteins; Bacteriological Techniques; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Glycolysis; Glyoxylates; Magnetic Phenomena; Membrane Transport Proteins; Oxygen; Pyruvaldehyde; Space Flight; Weightlessness
PubMed: 35163759
DOI: 10.3390/ijms23031837 -
ACS Nano Oct 2019Active transport of gas molecules is critical to preserve the physiological functions of organisms. Oxygen, as the most essential gas molecule, plays significant roles...
Active transport of gas molecules is critical to preserve the physiological functions of organisms. Oxygen, as the most essential gas molecule, plays significant roles in maintaining the metabolism and viability of cells. Herein, we report a nanomotor-based delivery system that combines the fast propulsion of acoustically propelled gold nanowire nanomotors (AuNW) with the high oxygen carrying capacity of red blood cell membrane-cloaked perfluorocarbon nanoemulsions (RBC-PFC) for active intracellular delivery of oxygen. The oxygen delivery capacity and kinetics of the AuNW nanomotors carrying RBC-PFC (denoted as "Motor-PFC") are examined under ultrasound field. Specifically, the fast movement of the Motor-PFC under an acoustic field accelerates intracellular delivery of oxygen to J774 macrophage cells. Upon entering the cells, the oxygen loaded in the Motor-PFC is sustainably released, which maintains the cell viability when cultured under hypoxic conditions. The acoustically propelled Motor-PFC leads to significantly higher cell viability (84.4%) over a 72 h period, compared to control samples with free RBC-PFC (44.4%) or to passive Motor-PFC (32.7%). These results indicate that the Motor-PFC can act as an effective delivery vehicle for active intracellular oxygen transport. While oxygen is used here as a model gas molecule, the Motor-PFC platform can be readily expanded to the active delivery of other gas molecules to various target cells.
Topics: Cell Hypoxia; Cell Survival; Emulsions; Kinetics; Nanowires; Oxygen
PubMed: 31556988
DOI: 10.1021/acsnano.9b06127 -
Proceedings of the National Academy of... Sep 2022Acute oxygen (O) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main...
Acute oxygen (O) sensing is essential for adaptation of organisms to hypoxic environments or medical conditions with restricted exchange of gases in the lung. The main acute O-sensing organ is the carotid body (CB), which contains neurosecretory chemoreceptor (glomus) cells innervated by sensory fibers whose activation by hypoxia elicits hyperventilation and increased cardiac output. Glomus cells have mitochondria with specialized metabolic and electron transport chain (ETC) properties. Reduced mitochondrial complex (MC) IV activity by hypoxia leads to production of signaling molecules (NADH and reactive O species) in MCI and MCIII that modulate membrane ion channel activity. We studied mice with conditional genetic ablation of MCIII that disrupts the ETC in the CB and other catecholaminergic tissues. Glomus cells survived MCIII dysfunction but showed selective abolition of responsiveness to hypoxia (increased [Ca] and transmitter release) with normal responses to other stimuli. Mitochondrial hypoxic NADH and reactive O species signals were also suppressed. MCIII-deficient mice exhibited strong inhibition of the hypoxic ventilatory response and altered acclimatization to sustained hypoxia. These data indicate that a functional ETC, with coupling between MCI and MCIV, is required for acute O sensing. O regulation of breathing results from the integrated action of mitochondrial ETC complexes in arterial chemoreceptors.
Topics: Animals; Cell Hypoxia; Electron Transport Complex III; Ion Channels; Mice; NAD; Oxygen; Respiration
PubMed: 36122208
DOI: 10.1073/pnas.2202178119 -
International Journal of Nanomedicine 2018Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly... (Review)
Review
Hypoxia exists to some degree in most solid tumors due to inadequate oxygen delivery of the abnormal vasculature which cannot meet the demands of the rapidly proliferating cancer cells. The levels of oxygenation within the same tumor are highly variable from one area to another and can change over time. Tumor hypoxia is an important impediment to effective cancer therapy. In radiotherapy, the primary mechanism is the creation of reactive oxygen species; hypoxic tumors are therefore radiation resistant. A number of chemotherapeutic drugs have been shown to be less effective when exposed to a hypoxic environment which can lead to further disease progression. Hypoxia is also a potent barrier to effective immunotherapy in cancer treatment. Because of the recognition of hypoxia as an important barrier to cancer treatment, a variety of approaches have been undertaken to overcome or reverse tumor hypoxia. Such approaches have included breathing hyperbaric oxygen, artificial hemoglobins, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). These approaches have largely failed due to limited efficacy and/or adverse side effects. Oxygen therapeutics, based on liquid FCs, can potentially increase the oxygen-carrying capacity of the blood to reverse tumor hypoxia. Currently, at least two drugs are in clinical trials to reverse tumor hypoxia; one of these is designed to improve permeability of oxygen into the tumor tissue and the other is based upon a low boiling point FC that transports higher amounts of oxygen per gram than previously tested FCs.
Topics: Animals; Cell Hypoxia; Humans; Immunotherapy; Neoplasms; Oxygen; Radiation-Sensitizing Agents; Tumor Hypoxia
PubMed: 30323592
DOI: 10.2147/IJN.S140462 -
Biochimica Et Biophysica Acta.... Aug 2020Mitochondrial uncoupling proteins (UCPs) play an essential role in dissipating the proton gradient and controlling the mitochondrial inner membrane potential. When...
Mitochondrial uncoupling proteins (UCPs) play an essential role in dissipating the proton gradient and controlling the mitochondrial inner membrane potential. When active, UCPs promote proton leak across the inner membrane, oxidative phosphorylation uncoupling, oxygen uptake increase and decrease the ATP synthesis. Invertebrates possess only isoforms UCP4 and UCP5, however, the role of these proteins is not clear in most species since it may depend on the physiological needs of each animal. This study presents the first functional characterization of crustacean uncoupling proteins from the white shrimp Litopenaeus vannamei LvUCP4 and LvUCP5. Free radicals production in various shrimp organs/tissues was first evaluated, and mitochondria were isolated from shrimp pleopods. The oxygen consumption rate, membrane potential and proton transport of the isolated non-phosphorylating mitochondria were used to determine LvUCPs activation/inhibition. Results indicate that UCPs activity is stimulated in the presence of 4-hydroxyl-2-nonenal (HNE) and myristic acid, and inhibited by the purine nucleotide GDP. A hypoxia/re-oxygenation assay was conducted to determine whether UCPs participate in shrimp mitochondria response to oxidative stress. Isolated mitochondria from shrimp at re-oxygenation produced large quantities of hydrogen peroxide and higher levels of both LvUCPs were immunodetected. Results suggest that, besides the active response of the shrimp antioxidant system, UCP-like activity is activated after hypoxia exposure and during re-oxygenation. LvUCPs may represent a mild uncoupling mechanism, which may be activated before the antioxidant system of cells, to early control reactive oxygen species production and oxidative damage in shrimp.
Topics: Animals; Hydrogen Peroxide; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Uncoupling Proteins; Oxygen; Penaeidae; Protons; Reactive Oxygen Species; Superoxide Dismutase
PubMed: 32305415
DOI: 10.1016/j.bbabio.2020.148209