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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria require NADPH for anti-oxidant protection and for specific biosynthetic pathways. However, the sources of mitochondrial NADPH and the mechanisms of maintaining mitochondrial redox balance are not well understood. We show here that in Saccharomyces cerevisiae, mitochondrial NADPH is largely provided by the product of the POS5 gene. We identified POS5 in a S.cerevisiae genetic screen for hyperoxia-sensitive mutants, or cells that cannot survive in 100% oxygen. POS5 encodes a protein that is homologous to NAD(+) and NADH kinases, and we show here that recombinant Pos5p has NADH kinase activity. Pos5p is localized to the mitochondrial matrix of yeast and appears to be important for several NADPH-requiring processes in the mitochondria, including resistance to a broad range of oxidative stress conditions, arginine biosynthesis and mitochondrial iron homeostasis. Pos5p represents the first member of the NAD(H) kinase family that has been identified as an important anti-oxidant factor and key source of the cellular reductant NADPH.
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PMID:A novel NADH kinase is the mitochondrial source of NADPH in Saccharomyces cerevisiae. 1272 69

Oxygen plays a central role in respiration of the cells and thus in generation of energy by aerobic metabolism. The cells precisely detect oxygen level and changes in oxygen perfusion leads to induction of various responses enabling to adapt to unfavorable conditions. CA IX carbonic anhydrase is a hypoxia-inducible tumor-associated antigen which is overexpressed in dense HeLa cells. Presented study investigates the effects of oxygen tension on CA IX expression in HeLa cell culture. Using of an immunoradiometric assay to quantify CA IX protein, it was revealed that expression of CA IX correlates with increasing cell density, lactate production and medium acidification under normoxic conditions. These observations and hypoxia-inducibility of CA IX suggested a possible role of pericellular hypoxia in density-induced CA IX expression. To test this hypothesis, HeLa cells were incubated in normobaric hyperoxia (50% O2) or cell culture medium was convected to disturb oxygen deprivation. Both approaches completely abrogated CA IX expression in dense HeLa cell cultures and therefore confirmed the importance of decreased oxygen tension in high cell density-induced CA IX expression. In addition, HeLa cells exposed to hyperoxia retained inducibility of CAIX expression by transition metals and iron chelators, suggesting that they act independently of cell density mediated-pO2-gradient or at a downstream site from oxygen sensor. Observed data indicate that high cell density-lowered pericellular pO2 is a crucial factor inducing CA IX expression and influencing composition of metabolic micromilieu surrounding the dense HeLa cells.
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PMID:High cell density-mediated pericellular hypoxia is a crucial factor inducing expression of the intrinsic hypoxia marker CA IX in vitro in HeLa cells. 1293 36

Heme oxygenases catalyze the rate-limiting step in heme degradation, resulting in the formation of carbon monoxide, iron and biliverdin that is subsequently reduced to bilirubin by biliverdin reductase. The products of this enzymatic reaction have important biological effects, including antioxidant, anti-inflammatory and cytoprotective functions. Three isoforms of heme oxygenase (HO) have been described: two constitutively expressed isoforms, HO-2 and HO-3, and an inducible isoform, HO-1 that is increased as an adaptive response to several injurious stimuli including heme, hyperoxia, hypoxia, endotoxin and heavy metals. Induction of HO-1 has been implicated in numerous clinically relevant disease states including transplant rejection, hypertension, atherosclerosis, lung injury, endotoxic shock and others. This review will focus on the protective functions of HO-1.
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PMID:Heme oxygenase-1 as a protective gene. 1549 91

We have shown previously with in vivo and in vitro animal models that the lens epithelium, in contrast to the nucleus, is remarkably resistant to hyperoxia. The main purpose of this study was to investigate the mRNA response of cultured human lens epithelial cells (LECs) to challenge by a high level of hyperbaric oxygen. Cells were treated for 3 hr with 50 atm of 99% O2, and then cultured normally for various times up to 11 days. Although the cells appeared normal immediately after the O2-treatment, they failed to grow and suffered 50% cell loss, as well as significant mitochondrial damage, during normal post-culture. Growth of the cells resumed after 3 days and by day 11, the number of O2-treated cells was the same as the controls. Remarkably, the 3 hr O2-treatment produced no immediate effects on either the cellular level of GSH, or on the activities of a number of antioxidant enzymes including glyceraldehyde-3-phosphate dehydrogenase, which is generally regarded as being highly sensitive to oxidation. In contrast, the activity of thioredoxin reductase (TrxR) was severely affected by the O2, decreasing by 51% after the 3 hr exposure. O2-induced death of the cells appeared to be caused by loss of ATP since a 31% decrease in ATP level occurred immediately after the O2-treatment, in spite of a 46% increase in lactate production. Analysis with real-time PCR showed a maximum 3-6-fold increase in mRNA levels 9 hr after the 3 hr O2-exposure for the enzymes heme oxygenase-1 (HO-1), MnSOD and TrxR1 (the cytoplasmic form of TrxR). These results were confirmed with the use of one-step RT-PCR and Northern blotting. Initial upregulation of message for HO-1 occurred a few hours before any upregulation of MnSOD could be detected, suggesting that release of free iron from the degradation of heme by HO-1 may have played a role in the upregulation of the dismutase. No significant changes in mRNA levels were observed for the antioxidant enzymes catalase, CuZnSOD, glutathione reductase and glutathione peroxidase, or for the antioxidant protein thioredoxin. Recovery of TrxR activity over a 4-day period appeared to parallel the return of the cells to a normal rate of growth. The results indicate that damaging effects of hyperoxia on cultured LECs occur primarily in the mitochondria, rather than in the cytoplasm. Cells avoid O2-induced cell death, and return to a normal rate of proliferation by upregulating mRNA levels for HO-1, MnSOD and TrxR1. It appears that full activity of TrxR1, an enzyme required for the production of deoxyribonucletides for DNA synthesis, is essential for the normal growth of O2-challenged LECs.
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PMID:Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. 1564 22

In this review the development of the concept 'hypoxia-reoxygenation injury' is outlined. An update of some important factors and mechanisms related to oxidative stress injury in newborn infants is presented, including the metabolism of glutathione, the role of antioxidants, iron and nitric oxide, and how these may influence health and disease in the newborn and contribute to 'oxygen radical disease of the newborn'. New insight into how hyperoxia and hypoxia may induce changes leading to retinopathy of prematurity by vascular endothelial growth factor acting in concert with insulin-like growth factor is briefly summarized. Inflammation and oxidative stress seem to be two sides of the same coin in newborn babies both contributing to injury partly through similar mechanisms.
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PMID:Oxidative stress in the newborn--a 30-year perspective. 1621 Aug 45

Two methods of the determination of lipid peroxidation products have been compared which are based on Fe(II) oxidation by them at acid pH values in the presence of xylenol orange which binds Fe(III) have been compared. The first method uses cumene hydropeoxide as an internal standard. In the second one, lipid peroxides are previously reduced by triphenylphosphine and these substances content is measured as a difference of the production of complexes with xylenol orange and iron ions in the control (with reduction) and experimental sample (without reduction). The optimization of measurement conditions is described. The levels of lipid peroxides in goldfish tissues assayed simultaneously by two methods were similar. The method with cumene hydroperoxide needs less amounts of biological material; moreover, there is no necessity in a calibration curve. Effects of hyperoxia on lipid peroxide levels in goldfish tissues were studied with the cumene method. Within the first hours of hyperoxia this index increased 13-times in the liver and 2-times in the brain and muscle. The further exposure rebounded this parameter to the initial level. Levels of lipid peroxides positively correlated with levels of end products of lipid peroxidation (thiobarbiturate acid reactive substances) in the goldfish tissues. The method of quantification of lipid peroxides with cumene is recommended for wide using in biological investigations.
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PMID:[Indices of oxidative stress. 2. Lipid peroxides]. 1749 27

Reactive Oxygen Spiecies (ROS) such as superoxide anion radical (.O(2)(-)) act as signals for the activation of stress-response and defense pathways. However, excess ROS generated by perturbing .O(2)(-) homeostasis stimulated many environmental stress, including intense light, drought, temperature stress, herbicides, induce high radical toxicity. Consequently, quantitative analysis of .O(2)(-) is a subject of intense research, since most of ROS are derived from .O(2)(-). Iron meso-tetrakis(3-thienyl)porphyrin complexes were electropolymerized onto a Au wire electrode. The modified Au electrode were applied to .O(2)(-) sensor to detect catalytic oxidation current of .O(2)(-) which was generated as an intermediate during the oxidation of xanthine by catalystic XOD. It was revealed that the sensor was quantitative to measure .O(2)(-). The modified Au electrode were applied to measure oxidation current of .O(2)(-) in mung beans under environmental stress condition. Plants were grown in atmosphere, 25 degrees C and in black darkness. The other plants were exposed to oxygen excess. The oxidation current of .O(2)(-) were increased plants were grown by high-oxygen environment compared to plants were grown at atmosphere. This experiment was indicated that environmental stress such as hyperoxia induced excess .O(2)(-) and Au wire sensor using iron porphyrin complexes is capable of .O(2)(-) detection in plants under environmental stresses.
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PMID:[Fabrication of sensor for reactive oxygen species using gold electrodes modified with electropolymerized porphyrins and application for detection of stress of plants]. 1789 67

Bilirubin is the end product of heme catabolism by heme oxygenases. The inducible form of these enzymes is heme oxygenase-1 (HO-1), which is the rate-limiting enzyme that can degrade heme into equimolar quantities of carbon monoxide (CO), biliverdin, and free iron. Biliverdin is very rapidly converted to bilirubin by the enzyme biliverdin reductase, and free iron upregulates the expression of ferritin. HO-1 is a ubiquitous stress protein and is induced in many cell types by various stimuli. Induced HO-1 exerts antiinflammatory effects and modulates apoptosis. Expression of HO-1 in vivo suppresses the inflammatory responses in endotoxic shock, hyperoxia, acute pleurisy, and organ transplantation, as well as ischemia-reperfusion injury, and thereby provides salutary effects in these conditions. Accumulating evidence indicates that biliverdin/bilirubin can mediate the protective effects of HO-1 in many disease models, such as IRI and organ transplantation, via its antiinflammatory, antiapoptotic, antiproliferative, and antioxidant properties, as well as its effects on the immune response. This review attempts to summarize these protective roles as well as the molecular mechanisms by which biliverdin/bilirubin benefit IRI and solid-organ transplantation, including chronic rejection, and islet transplantation.
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PMID:Therapeutic applications of bilirubin and biliverdin in transplantation. 1791 67

Platelet-derived growth factors (PDGF) play a major role in pericyte recruitment in tumor capillaries. Pericytes are required for proper vessel development, and contribute to tumor angiogenesis by promoting stabilization and maturation of newly formed vessels. To investigate the effects of pericyte coverage on tumor vessel morphology and function in vivo, tumors derived from B16 melanoma cells transfected with either control plasmid (B16/ctr) or plasmid encoding full-length PDGF-BB (B16/PDGF), the latter previously shown to have enhanced blood vessel pericyte coverage and an increased tumor growth rate, were assessed using histopathological methods, Hoechst 33342-based perfusion analyses, and two noninvasive susceptibility magnetic resonance imaging (MRI) methods. Susceptibility-contrast MRI, incorporating the use of ultrasmall superparamagnetic iron oxide particles, revealed a significant (p < 0.05) reduction in vessel size index (R(v)) of B16/PDGF tumors, and which was validated histologically by the presence of significantly smaller (p < 0.001), more punctate blood vessels identified by fluorescence microscopy of the perfusion marker Hoechst 33342. Intrinsic-susceptibility MRI was used to measure the transverse MRI relaxation rate R(2)*, sensitive to changes in endogenous paramagnetic [deoxyhaemoglobin], and used to probe for vascular maturation and function. Hypercapnia (5% CO(2)/95% air) induced a negligible Delta R(2)* response in the B16/ctr and B16/PDGF tumors. In contrast, hyperoxia (5% CO(2)/95% O(2)) induced a significantly greater R(2)* reduction in the B16/PDGF tumors (p < 0.02). Together the susceptibility MRI-derived biomarkers reveal novel pericyte-dependent changes in the morphology and function of the perfused tumor vasculature in vivo.
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PMID:The effects of tumor-derived platelet-derived growth factor on vascular morphology and function in vivo revealed by susceptibility MRI. 1803 83

Vitamin A (retinol), vitamin C (ascorbic acid), and vitamin E (alpha-tocopherol) are each thought to play an important role in the aging process. Here, we investigated the effects of these vitamins on Drosophila melanogaster life span under different oxidative stress conditions. Among the vitamins tested, alpha-tocopherol exhibited the strongest antioxidant activity, extending average and maximum life span for wild-type flies under hyperoxia and for Cu/Zn superoxide dismutase-deficient (SOD1-deficient) flies under normoxia. Retinol supplementation extended life span of SOD1-deficient flies under normoxia, and ascorbic acid supplementation extended life span of wild-type flies under normoxia. However, both retinol and ascorbic acid exhibited a strong prooxidant activity under hyperoxia and shortened life span. Furthermore, ascorbic acid supplementation enhanced the toxic effects of iron, with the iron pool significantly increased in adult whole-body extracts. Taken together, our results document antioxidant and prooxidant contributions of vitamins to D. melanogaster life-span determination under normoxia and under oxidative stress.
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PMID:The effects of vitamin supplementation on Drosophila life span under normoxia and under oxidative stress. 1824 58


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