Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia?

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Rieger, Christina T; Fiegl, Michael

2016-07-01

Reduced oxygen partial pressure (pO2) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1α) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO2. However, in contrast to solid tumors, in this context, the low pO2 is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO2 as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO2. Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO2: they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO2 should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms; therefore, a strict distinction should be made between physiologically low pO2 (physoxia) and hypoxia. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Influence of variable oxygen concentration on the response of cells to heat or x irradiation

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Gerweck, L.E.; Richards, B.; Jennings, M.

1981-01-01

The influence of oxygen concentration on the lethal response of cells exposed to 43 0 C hyperthermia was determined and compared to the response of cells exposed to radiation under equivalent culturing and environmental conditions. Chinese hamster ovary (CHO) cells were heated or irradiated 0.5 h after induction of hypoxia and then reoxygenated following treatment. The oxygen enhancement ratio (OER) for heat or radiation was determined at the 1% survival level from least-squares fit of survival curves. A maximum OER of 3.1 +- 0.2 was observed in the 20 to 95% oxygen concentration range. The OER for heat, however, was 1.0 +- 0.1 irrespective of the gas-phase oxygen concentration. These results show that the lethal effects of heat are not influenced by the oxygen concentration at the time of treatment in CHO cells exposed to 43 0 C hyperthermia

Cell physiology regulation by hypoxia inducible factor-1: Targeting oxygen-related nanomachineries of hypoxic cells.

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Eskandani, Morteza; Vandghanooni, Somayeh; Barar, Jaleh; Nazemiyeh, Hossein; Omidi, Yadollah

2017-06-01

Any dysfunctionality in maintaining the oxygen homeostasis by mammalian cells may elicit hypoxia/anoxia, which results in inescapable oxidative stress and possible subsequent detrimental impacts on certain cells/tissues with high demands to oxygen molecules. The ischemic damage in turn can trigger initiation of a number of diseases including organs ischemia, metabolic disorders, inflammatory diseases, different types of malignancies, and alteration in wound healing process. Thus, full comprehension of molecular mechanism(s) and cellular physiology of the oxygen homeostasis is the cornerstone of the mammalian cells metabolism, energetic pathways and health and disease conditions. An imbalance in oxygen content within the cellular microenvironment activates a cascade of molecular events that are often compensated, otherwise pathologic condition occurs through a complexed network of biomolecules. Hypoxia inducible factor-1 (HIF-1) plays a key transcriptional role in the adaptation of cell physiology in relation with the oxygen content within a cell. In this current study, we provide a comprehensive review on the molecular mechanisms of oxygen sensing and homeostasis and the impacts of HIF-1 in hypoxic/anoxic conditions. Moreover, different molecular and biochemical responses of the cells to the surrounding environment are discussed in details. Finally, modern technological approaches for targeting the hypoxia related proteins are articulated. Copyright © 2017. Published by Elsevier B.V.

Structural and functional analysis of coral Hypoxia Inducible Factor.

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Didier Zoccola

Full Text Available Tissues of symbiotic Cnidarians are exposed to wide, rapid and daily variations of oxygen concentration. Indeed, during daytime, intracellular O2 concentration increases due to symbiont photosynthesis, while during night, respiration of both host cells and symbionts leads to intra-tissue hypoxia. The Hypoxia Inducible Factor 1 (HIF-1 is a heterodimeric transcription factor used for maintenance of oxygen homeostasis and adaptation to hypoxia. Here, we carried out a mechanistic study of the response to variations of O2 concentrations of the coral model Stylophora pistillata. In silico analysis showed that homologs of HIF-1 α (SpiHIF-1α and HIF-1β (SpiHIF-1β exist in coral. A specific SpiHIF-1 DNA binding on mammalian Hypoxia Response Element (HRE sequences was shown in extracts from coral exposed to dark conditions. Then, we cloned the coral HIF-1α and β genes and determined their expression and transcriptional activity. Although HIF-1α has an incomplete Oxygen-dependent Degradation Domain (ODD relative to its human homolog, its protein level is increased under hypoxia when tested in mammalian cells. Moreover, co-transfection of SpiHIF-1α and β in mammalian cells stimulated an artificial promoter containing HRE only in hypoxic conditions. This study shows the strong conservation of molecular mechanisms involved in adaptation to O2 concentration between Cnidarians and Mammals whose ancestors diverged about 1,200-1,500 million years ago.

Structural and functional analysis of coral Hypoxia Inducible Factor.

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Zoccola, Didier; Morain, Jonas; Pagès, Gilles; Caminiti-Segonds, Natacha; Giuliano, Sandy; Tambutté, Sylvie; Allemand, Denis

2017-01-01

Tissues of symbiotic Cnidarians are exposed to wide, rapid and daily variations of oxygen concentration. Indeed, during daytime, intracellular O2 concentration increases due to symbiont photosynthesis, while during night, respiration of both host cells and symbionts leads to intra-tissue hypoxia. The Hypoxia Inducible Factor 1 (HIF-1) is a heterodimeric transcription factor used for maintenance of oxygen homeostasis and adaptation to hypoxia. Here, we carried out a mechanistic study of the response to variations of O2 concentrations of the coral model Stylophora pistillata. In silico analysis showed that homologs of HIF-1 α (SpiHIF-1α) and HIF-1β (SpiHIF-1β) exist in coral. A specific SpiHIF-1 DNA binding on mammalian Hypoxia Response Element (HRE) sequences was shown in extracts from coral exposed to dark conditions. Then, we cloned the coral HIF-1α and β genes and determined their expression and transcriptional activity. Although HIF-1α has an incomplete Oxygen-dependent Degradation Domain (ODD) relative to its human homolog, its protein level is increased under hypoxia when tested in mammalian cells. Moreover, co-transfection of SpiHIF-1α and β in mammalian cells stimulated an artificial promoter containing HRE only in hypoxic conditions. This study shows the strong conservation of molecular mechanisms involved in adaptation to O2 concentration between Cnidarians and Mammals whose ancestors diverged about 1,200-1,500 million years ago.

Effect of different concentrations of oxygen on expression of sigma 1 receptor and superoxide dismutases in human colon adenocarcinoma cell lines.

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Skrzycki, Michał; Czeczot, Hanna; Mielczarek-Puta, Magdalena; Otto-Ślusarczyk, Dagmara; Graboń, Wojciech

2017-06-01

Tumor cells due to distance from capillary vessels exist in different oxygenation conditions (anoxia, hypoxia, normoxia). Changes in cell oxygenation lead to reactive oxygen species production and oxidative stress. Sigma 1 receptor (Sig1R) is postulated to be stress responding agent and superoxide dismutases (SOD1 and SOD2) are key antioxidant enzymes. It is possible that they participate in tumor cells adaptation to different concentrations of oxygen. Evaluation of Sig1R, SOD1, and SOD2 expression in different concentrations of oxygen (1%, 10%, 21%) in colon adenocarcinoma cell lines. SW480 (primary adenocarcinoma) and SW620 (metastatic) cell lines were cultured in standard conditions in Dulbecco's modified Eagle's medium for 5 days, and next cultured in Hypoxic Chamber in 1% O 2 , 10% O 2 , 21% O 2 . Number of living cells was determined by trypan blue assay. Level of mRNA for Sig1R, SOD1, and SOD2 was determined by standard PCR method. Statistical analysis was conducted using Statistica 10.1 software. We observed significant changes in expression of Sig1R, SOD1, SOD2 due to different oxygen concentrations. ANOVA analysis revealed significant interactions between studied parameters mainly in hypoxia conditions in SW480 cells and between Sig1R and SOD2 in SW620 cells. It also showed that changes in expression of studied proteins depend significantly on type of the cell line. Changes of Sig1R and SOD2 expression point to mitochondria as main organelle responsible for survival of tumor cells exposed to hypoxia or oxidative stress. Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen.

Hypoxia signaling pathways: modulators of oxygen-related organelles

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Schönenberger, Miriam J.; Kovacs, Werner J.

2015-01-01

Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1α and EPAS1/HIF-2α) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-α signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF-1α in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1α activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2α as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2α activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2α might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2α-mediated pexophagy for human health. PMID:26258123

A genetically encoded biosensor for visualising hypoxia responses in vivo

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Tvisha Misra

2017-02-01

Full Text Available Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia rely on the conserved hypoxia-inducible factor 1 (HIF-1. Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response.

The oxygen effect and cellular adaptation

International Nuclear Information System (INIS)

Meshcherikova, V.V.; Vajnson, A.A.; Yarmonenko, S.P.

1979-01-01

The radiomodifying effect of oxygen was shown to depend on the level of cellular oxygenation prior to irradiation. Acute hypoxia created at the time of irradiation protects previously normally oxygenated cells with DMF approximately 1.4 times larger than that of cells cultured for 24 hours under conditions of mild hypoxia. It is suggested that a decrease in the radioprotective effect of acute hypoxia on chronically hypoxic cells is correlated with an appreciable decrease in the rate of oxygen consumption by these cells, due to which the oxygen concentration near the intracellular targets in chronically hypoxic cells may be higher than in normal cells under conditions of poor oxygenation

Effects of natural and human-induced hypoxia on coastal benthos

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Levin, L. A.; Ekau, W.; Gooday, A. J.; Jorissen, F.; Middelburg, J. J.; Naqvi, S. W. A.; Neira, C.; Rabalais, N. N.; Zhang, J.

2009-10-01

Coastal hypoxia (defined here as branchial structures, predominate. Large taxa are more sensitive than small taxa to hypoxia. Crustaceans and echinoderms are typically more sensitive to hypoxia, with lower oxygen thresholds, than annelids, sipunculans, molluscs and cnidarians. Mobile fish and shellfish will migrate away from low-oxygen areas. Within a species, early life stages may be more subject to oxygen stress than older life stages. Hypoxia alters both the structure and function of benthic communities, but effects may differ with regional hypoxia history. Human-caused hypoxia is generally linked to eutrophication, and occurs adjacent to watersheds with large populations or agricultural activities. Many occurrences are seasonal, within estuaries, fjords or enclosed seas of the North Atlantic and the NW Pacific Oceans. Benthic faunal responses, elicited at oxygen levels below 2 ml L-1, typically involve avoidance or mortality of large species and elevated abundances of enrichment opportunists, sometimes prior to population crashes. Areas of low oxygen persist seasonally or continuously beneath upwelling regions, associated with the upper parts of oxygen minimum zones (SE Pacific, W Africa, N Indian Ocean). These have a distribution largely distinct from eutrophic areas and support a resident fauna that is adapted to survive and reproduce at oxygen concentrations <0.5 ml L-1. Under both natural and eutrophication-caused hypoxia there is loss of diversity, through attrition of intolerant species and elevated dominance, as well as reductions in body size. These shifts in species composition and diversity yield altered trophic structure, energy flow pathways, and corresponding ecosystem services such as production, organic matter cycling and organic C burial. Increasingly the influences of nature and humans interact to generate or exacerbate hypoxia. A warmer ocean is more stratified, holds less oxygen, and may experience greater advection of oxygen-poor source

Ecosystem impacts of hypoxia: thresholds of hypoxia and pathways to recovery

International Nuclear Information System (INIS)

Steckbauer, A; Duarte, C M; Vaquer-Sunyer, R; Carstensen, J; Conley, D J

2011-01-01

Coastal hypoxia is increasing in the global coastal zone, where it is recognized as a major threat to biota. Managerial efforts to prevent hypoxia and achieve recovery of ecosystems already affected by hypoxia are largely based on nutrient reduction plans. However, these managerial efforts need to be informed by predictions on the thresholds of hypoxia (i.e. the oxygen levels required to conserve biodiversity) as well as the timescales for the recovery of ecosystems already affected by hypoxia. The thresholds for hypoxia in coastal ecosystems are higher than previously thought and are not static, but regulated by local and global processes, being particularly sensitive to warming. The examination of recovery processes in a number of coastal areas managed for reducing nutrient inputs and, thus, hypoxia (Northern Adriatic; Black Sea; Baltic Sea; Delaware Bay; and Danish Coastal Areas) reveals that recovery timescales following the return to normal oxygen conditions are much longer than those of loss following the onset of hypoxia, and typically involve decadal timescales. The extended lag time for ecosystem recovery from hypoxia results in non-linear pathways of recovery due to hysteresis and the shift in baselines, affecting the oxygen thresholds for hypoxia through time.

Effects of natural and human-induced hypoxia on coastal benthos

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L. A. Levin

2009-10-01

Full Text Available Coastal hypoxia (defined here as <1.42 ml L⁻¹; 62.5 μM; 2 mg L⁻¹, approx. 30% oxygen saturation develops seasonally in many estuaries, fjords, and along open coasts as a result of natural upwelling or from anthropogenic eutrophication induced by riverine nutrient inputs. Permanent hypoxia occurs naturally in some isolated seas and marine basins as well as in open slope oxygen minimum zones. Responses of benthos to hypoxia depend on the duration, predictability, and intensity of oxygen depletion and on whether H₂S is formed. Under suboxic conditions, large mats of filamentous sulfide oxidizing bacteria cover the seabed and consume sulfide. They are hypothesized to provide a detoxified microhabitat for eukaryotic benthic communities. Calcareous foraminiferans and nematodes are particularly tolerant of low oxygen concentrations and may attain high densities and dominance, often in association with microbial mats. When oxygen is sufficient to support metazoans, small, soft-bodied invertebrates (typically annelids, often with short generation times and elaborate branchial structures, predominate. Large taxa are more sensitive than small taxa to hypoxia. Crustaceans and echinoderms are typically more sensitive to hypoxia, with lower oxygen thresholds, than annelids, sipunculans, molluscs and cnidarians. Mobile fish and shellfish will migrate away from low-oxygen areas. Within a species, early life stages may be more subject to oxygen stress than older life stages.

Hypoxia alters both the structure and function of benthic communities, but effects may differ with regional hypoxia history. Human-caused hypoxia is generally linked to eutrophication, and occurs adjacent to watersheds with large populations or agricultural activities. Many occurrences are seasonal, within estuaries, fjords or enclosed seas of the North Atlantic and the NW Pacific Oceans. Benthic faunal responses, elicited at oxygen levels below

In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.

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Uddin, Md Imam; Evans, Stephanie M; Craft, Jason R; Capozzi, Megan E; McCollum, Gary W; Yang, Rong; Marnett, Lawrence J; Uddin, Md Jashim; Jayagopal, Ashwath; Penn, John S

2016-08-05

Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs.

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

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Khadjavi, Amina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Magnetto, Chiara [Istituto Nazionale di Ricerca Metrologica (INRIM), Torino (Italy); Panariti, Alice [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Argenziano, Monica [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Gulino, Giulia Rossana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Rivolta, Ilaria [Dipartimento di Scienze della Salute, Università di Milano Bicocca, Monza (Italy); Cavalli, Roberta [Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Torino (Italy); Giribaldi, Giuliana [Dipartimento di Oncologia, Università di Torino, Torino (Italy); Guiot, Caterina [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Prato, Mauro, E-mail: mauro.prato@unito.it [Dipartimento di Neuroscienze, Università di Torino, Torino (Italy); Dipartimento di Scienze della Sanità Pubblica e Pediatriche, Università di Torino, Torino (Italy)

2015-08-01

Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic

Chitosan-shelled oxygen-loaded nanodroplets abrogate hypoxia dysregulation of human keratinocyte gelatinases and inhibitors: New insights for chronic wound healing

International Nuclear Information System (INIS)

Khadjavi, Amina; Magnetto, Chiara; Panariti, Alice; Argenziano, Monica; Gulino, Giulia Rossana; Rivolta, Ilaria; Cavalli, Roberta; Giribaldi, Giuliana; Guiot, Caterina; Prato, Mauro

2015-01-01

Background: : In chronic wounds, efficient epithelial tissue repair is hampered by hypoxia, and balances between the molecules involved in matrix turn-over such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are seriously impaired. Intriguingly, new oxygenating nanocarriers such as 2H,3H-decafluoropentane-based oxygen-loaded nanodroplets (OLNs) might effectively target chronic wounds. Objective: : To investigate hypoxia and chitosan-shelled OLN effects on MMP/TIMP production by human keratinocytes. Methods: : HaCaT cells were treated for 24 h with 10% v/v OLNs both in normoxia or hypoxia. Cytotoxicity and cell viability were measured through biochemical assays; cellular uptake by confocal microscopy; and MMP and TIMP production by enzyme-linked immunosorbent assay or gelatin zymography. Results: : Normoxic HaCaT cells constitutively released MMP-2, MMP-9, TIMP-1 and TIMP-2. Hypoxia strongly impaired MMP/TIMP balances by reducing MMP-2, MMP-9, and TIMP-2, without affecting TIMP-1 release. After cellular uptake by keratinocytes, nontoxic OLNs abrogated all hypoxia effects on MMP/TIMP secretion, restoring physiological balances. OLN abilities were specifically dependent on time-sustained oxygen diffusion from OLN core. Conclusion: : Chitosan-shelled OLNs effectively counteract hypoxia-dependent dysregulation of MMP/TIMP balances in human keratinocytes. Therefore, topical administration of exogenous oxygen, properly encapsulated in nanodroplet formulations, might be a promising adjuvant approach to promote healing processes in hypoxic wounds. - Highlights: • Hypoxia impairs MMP9/TIMP1 and MMP2/TIMP2 balances in HaCaT human keratinocytes. • Chitosan-shelled oxygen-loaded nanodroplets (OLNs) are internalised by HaCaT cells. • OLNs are not toxic to HaCaT cells. • OLNs effectively counteract hypoxia effects on MMP/TIMP balances in HaCaT cells. • OLNs appear as promising and cost-effective therapeutic tools for hypoxic

Hypoxia dysregulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes

International Nuclear Information System (INIS)

Chen Baoying; Lam, Karen S.L.; Wang Yu; Wu Donghai; Lam, Michael C.; Shen Jiangang; Wong Laiching; Hoo, Ruby L.C.; Zhang Jialiang; Xu Aimin

2006-01-01

Low plasma levels of adiponectin (hypoadiponectinemia) and elevated circulating concentrations of plasminogen activator inhibitor (PAI)-1 are causally associated with obesity-related insulin resistance and cardiovascular disease. However, the mechanism that mediates the aberrant production of these two adipokines in obesity remains poorly understood. In this study, we investigated the effects of hypoxia and reactive oxygen species (ROS) on production of adiponectin and PAI-1 in 3T3-L1 adipocytes. Quantitative PCR and immunoassays showed that ambient hypoxia markedly suppressed adiponectin mRNA expression and its protein secretion, and increased PAI-1 production in mature adipocytes. Dimethyloxallyl glycine, a stabilizer of hypoxia-inducible factor 1α (HIF-1α), mimicked the hypoxia-mediated modulations of these two adipokines. Hypoxia caused a modest elevation of ROS in adipocytes. However, ablation of intracellular ROS by antioxidants failed to alleviate hypoxia-induced aberrant production of adiponectin and PAI-1. On the other hand, the antioxidants could reverse hydrogen peroxide (H 2 O 2 )-induced dysregulation of adiponectin and PAI-1 production. H 2 O 2 treatment decreased the expression levels of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein (C/EBPα), but had no effect on HIF-1α, whereas hypoxia stabilized HIF-1α and decreased expression of C/EBPα, but not PPARγ. Taken together, these data suggest that hypoxia and ROS decrease adiponectin production and augment PAI-1 expression in adipocytes via distinct signaling pathways. These effects may contribute to hypoadiponectinemia and elevated PAI-1 levels in obesity, type 2 diabetes, and cardiovascular diseases

Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia.

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Lim, Diane C; Brady, Daniel C; Po, Pengse; Chuang, Li Pang; Marcondes, Laise; Kim, Emily Y; Keenan, Brendan T; Guo, Xiaofeng; Maislin, Greg; Galante, Raymond J; Pack, Allan I

2015-03-01

Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12-iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12-iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions. Copyright © 2015 the American Physiological Society.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

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Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

Frequently asked questions in hypoxia research

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Wenger RH

2015-09-01

Full Text Available Roland H Wenger,1,2 Vartan Kurtcuoglu,1,2 Carsten C Scholz,1,2 Hugo H Marti,3 David Hoogewijs1,2,4 1Institute of Physiology and Zurich Center for Human Physiology (ZIHP, University of Zurich, 2National Center of Competence in Research “Kidney.CH”, Zurich, Switzerland; 3Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, 4Institute of Physiology, University of Duisburg-Essen, Essen, Germany Abstract: “What is the O2 concentration in a normoxic cell culture incubator?” This and other frequently asked questions in hypoxia research will be answered in this review. Our intention is to give a simple introduction to the physics of gases that would be helpful for newcomers to the field of hypoxia research. We will provide background knowledge about questions often asked, but without straightforward answers. What is O2 concentration, and what is O2 partial pressure? What is normoxia, and what is hypoxia? How much O2 is experienced by a cell residing in a culture dish in vitro vs in a tissue in vivo? By the way, the O2 concentration in a normoxic incubator is 18.6%, rather than 20.9% or 20%, as commonly stated in research publications. And this is strictly only valid for incubators at sea level. Keywords: gas laws, hypoxia-inducible factor, Krogh tissue cylinder, oxygen diffusion, partial pressure, tissue oxygen levels

Emerging roles of hypoxia-inducible factors and reactive oxygen species in cancer and pluripotent stem cells

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Shigeo Saito

2015-06-01

Full Text Available Eukaryotic organisms require oxygen homeostasis to maintain proper cellular function for survival. During conditions of low oxygen tension (hypoxia, cells activate the transcription of genes that induce an adaptive response, which supplies oxygen to tissues. Hypoxia and hypoxia-inducible factors (HIFs may contribute to the maintenance of putative cancer stem cells, which can continue self-renewal indefinitely and express stemness genes in hypoxic stress environments (stem cell niches. Reactive oxygen species (ROS have long been recognized as toxic by-products of aerobic metabolism that are harmful to living cells, leading to DNA damage, senescence, or cell death. HIFs may promote a cancer stem cell state, whereas the loss of HIFs induces the production of cellular ROS and activation of proteins p53 and p16Ink4a, which lead to tumor cell death and senescence. ROS seem to inhibit HIF regulation in cancer cells. By contrast, controversial data have suggested that hypoxia increases the generation of ROS, which prevents hydroxylation of HIF proteins by inducing their transcription as negative feedback. Moreover, hypoxic conditions enhance the generation of induced pluripotent stem cells (iPSCs. During reprogramming of somatic cells into a PSC state, cells attain a metabolic state typically observed in embryonic stem cells (ESCs. ESCs and iPSCs share similar bioenergetic metabolisms, including decreased mitochondrial number and activity, and induced anaerobic glycolysis. This review discusses the current knowledge regarding the emerging roles of ROS homeostasis in cellular reprogramming and the implications of hypoxic regulation in cancer development.

Mitochondrial Signaling in Plants Under Hypoxia: Use of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS)

DEFF Research Database (Denmark)

Hebelstrup, Kim; Møller, Ian Max

2015-01-01

Hypoxia commonly occurs in roots in water-saturated soil and in maturing and germinating seeds. We here review the role of the mitochondria in the cellular response to hypoxia with an emphasis on the turnover of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) and their potential...

Systemic oxidative-nitrosative-inflammatory stress during acute exercise in hypoxia; implications for microvascular oxygenation and aerobic capacity.

Science.gov (United States)

Woodside, John D S; Gutowski, Mariusz; Fall, Lewis; James, Philip E; McEneny, Jane; Young, Ian S; Ogoh, Shigehiko; Bailey, Damian M

2014-12-01

Exercise performance in hypoxia may be limited by a critical reduction in cerebral and skeletal tissue oxygenation, although the underlying mechanisms remain unclear. We examined whether increased systemic free radical accumulation during hypoxia would be associated with elevated microvascular deoxygenation and reduced maximal aerobic capacity (V̇O2 max ). Eleven healthy men were randomly assigned single-blind to an incremental semi-recumbent cycling test to determine V̇O2 max in both normoxia (21% O2) and hypoxia (12% O2) separated by a week. Continuous-wave near-infrared spectroscopy was employed to monitor concentration changes in oxy- and deoxyhaemoglobin in the left vastus lateralis muscle and frontal cerebral cortex. Antecubital venous blood samples were obtained at rest and at V̇O2 max to determine oxidative (ascorbate radical by electron paramagnetic resonance spectroscopy), nitrosative (nitric oxide metabolites by ozone-based chemiluminescence and 3-nitrotyrosine by enzyme-linked immunosorbent assay) and inflammatory stress biomarkers (soluble intercellular/vascular cell adhesion 1 molecules by enzyme-linked immunosorbent assay). Hypoxia was associated with increased cerebral and muscle tissue deoxygenation and lower V̇O2 max (P exercise-induced increase in oxidative-nitrosative-inflammatory stress, hypoxia per se did not have an additive effect (P > 0.05 versus normoxia). Consequently, we failed to observe correlations between any metabolic, haemodynamic and cardiorespiratory parameters (P > 0.05). Collectively, these findings suggest that altered free radical metabolism cannot explain the elevated microvascular deoxygenation and corresponding lower V̇O2 max in hypoxia. Further research is required to determine whether free radicals when present in excess do indeed contribute to the premature termination of exercise in hypoxia. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.

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Banh, Robert S; Iorio, Caterina; Marcotte, Richard; Xu, Yang; Cojocari, Dan; Rahman, Anas Abdel; Pawling, Judy; Zhang, Wei; Sinha, Ankit; Rose, Christopher M; Isasa, Marta; Zhang, Shuang; Wu, Ronald; Virtanen, Carl; Hitomi, Toshiaki; Habu, Toshiyuki; Sidhu, Sachdev S; Koizumi, Akio; Wilkins, Sarah E; Kislinger, Thomas; Gygi, Steven P; Schofield, Christopher J; Dennis, James W; Wouters, Bradly G; Neel, Benjamin G

2016-07-01

Tumours exist in a hypoxic microenvironment and must limit excessive oxygen consumption. Hypoxia-inducible factor (HIF) controls mitochondrial oxygen consumption, but how/if tumours regulate non-mitochondrial oxygen consumption (NMOC) is unknown. Protein-tyrosine phosphatase-1B (PTP1B) is required for Her2/Neu-driven breast cancer (BC) in mice, although the underlying mechanism and human relevance remain unclear. We found that PTP1B-deficient HER2(+) xenografts have increased hypoxia, necrosis and impaired growth. In vitro, PTP1B deficiency sensitizes HER2(+) BC lines to hypoxia by increasing NMOC by α-KG-dependent dioxygenases (α-KGDDs). The moyamoya disease gene product RNF213, an E3 ligase, is negatively regulated by PTP1B in HER2(+) BC cells. RNF213 knockdown reverses the effects of PTP1B deficiency on α-KGDDs, NMOC and hypoxia-induced death of HER2(+) BC cells, and partially restores tumorigenicity. We conclude that PTP1B acts via RNF213 to suppress α-KGDD activity and NMOC. This PTP1B/RNF213/α-KGDD pathway is critical for survival of HER2(+) BC, and possibly other malignancies, in the hypoxic tumour microenvironment.

Effects of hypoxia on dopamine concentration and the immune response of White Shrimp ( Litopenaeus vannamei)

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Hu, Fawen; Pan, Luqing; Jing, Futao

2009-03-01

Effects of hypoxia on the dopamine concentration and the immune response of White Shrimp Litopenaeus vannamei were studied. The results showed that hypoxia had significant effects on the concentration of dopamine (DA) in the haemolymph, haemocyte count, phenoloxidase activity, phagocytic activity of haemocytes and bacteriolytic and antibacterial activity in the haemolymph ( P<0.05). The concentration of the dopamine in haemolymph reached its maximum in the 3.0 and 1.5 mg L-1 DO groups at 12 h and 6 h, and then returned to normal after 24 h and 12 h, respectively. All immune parameters decreased with the reduction of dissolved oxygen. Total haemocyte count (THC), the hyaline cells and semi-granular cells in the 3.0 mg L-1 DO group became stable after 12 h, while granular cells did so after 24 h. The THC and different haemocyte count (DHC) in the 1.5 mg L-1 DO group became stable after 24 h. Phenoloxidase activity and bacteriolytic activity in the 3.0 and 1.5 mg L-1 DO groups reached their stable levels after 24 h and 12 h respectively, while phagocytic activity and antibacterial activity became stable after 24 and 12, and 36 and 24 h, respectively. It was also indicated that the changes of dopamine concentrations in haemolymph, haemocyte count and phenoloxidase activity were obviously related to the exposure time under hypoxic conditions.

Effect of acadesine on breast cancer cells under hypoxia

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A. M. Shcherbakov

2017-01-01

Full Text Available The riboside derivative acadesine (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside is currently being tested in clinical trials as a promising anti-tumor drug. Intracellular target of acadesine is adenosine monophosphate-activated protein kinase (АМРК, an important regulatory molecule of energy metabolism. It is expected that acadesine would be active in tumors under hypoxia conditions. In normoxia (cells incubated in 21 % oxygen, acadesine inhibited proliferation and induced cell death of breast adenocarcinoma, including the triple negative breast cancer line. When oxygen partial pressure was decreased to 1 % (experimental hypoxia, acadesine inhibited activation of reporter construct responsive to HIF-1α (hypoxia inducible factor 1 alpha transcription factor. This effect was observed for acadesine in concentrations close to cytotoxic. Acadesine retained cytotoxicity under hypoxia and decreased the survival of the MDA-MB-231 cell line when used in combination with cisplatin. These results considerably widen acadesine’s field of application and allow to assume its efficacy in chemotherapy combination regimens for breast cancer, including the tumors with low oxygenation.

Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter

Science.gov (United States)

2012-01-01

Background Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p proteomics datasets for all time points. The lack of correlation between some transcript levels and their subsequent protein levels suggests another regulatory layer of the hypoxia response in A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As

Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter

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Barker Bridget M

2012-02-01

Full Text Available Abstract Background Aspergillus fumigatus is a mold responsible for the majority of cases of aspergillosis in humans. To survive in the human body, A. fumigatus must adapt to microenvironments that are often characterized by low nutrient and oxygen availability. Recent research suggests that the ability of A. fumigatus and other pathogenic fungi to adapt to hypoxia contributes to their virulence. However, molecular mechanisms of A. fumigatus hypoxia adaptation are poorly understood. Thus, to better understand how A. fumigatus adapts to hypoxic microenvironments found in vivo during human fungal pathogenesis, the dynamic changes of the fungal transcriptome and proteome in hypoxia were investigated over a period of 24 hours utilizing an oxygen-controlled fermenter system. Results Significant increases in transcripts associated with iron and sterol metabolism, the cell wall, the GABA shunt, and transcriptional regulators were observed in response to hypoxia. A concomitant reduction in transcripts was observed with ribosome and terpenoid backbone biosynthesis, TCA cycle, amino acid metabolism and RNA degradation. Analysis of changes in transcription factor mRNA abundance shows that hypoxia induces significant positive and negative changes that may be important for regulating the hypoxia response in this pathogenic mold. Growth in hypoxia resulted in changes in the protein levels of several glycolytic enzymes, but these changes were not always reflected by the corresponding transcriptional profiling data. However, a good correlation overall (R2 = 0.2, p A. fumigatus. Conclusions Taken together, our data suggest a robust cellular response that is likely regulated both at the transcriptional and post-transcriptional level in response to hypoxia by the human pathogenic mold A. fumigatus. As with other pathogenic fungi, the induction of glycolysis and transcriptional down-regulation of the TCA cycle and oxidative phosphorylation appear to major

Radiosensitivity of Hela cells in various O2 concentrations and consideration of oxygen effect in radiotherapy

International Nuclear Information System (INIS)

Kuroda, Yoshikazu; Nyunoya, Koichiro

1979-01-01

The aim of this paper is the study of the radiosensitivity of HeLa cells in vitro in various oxygen concentrations and the consideration of the utilization of oxygen effect in radiation therapy, based on the data of HeLa cells and tumor oxygen tension. Survival curves of HeLa cells are found to be exponential as a function of radiation dose and the radiosensitivity is dependent on oxygen tension of culture medium. Relative radiosensitivity decreases remarkably at low level of oxygen, especially under 9 mmHg pO 2 . The utilization of oxygen effect in radiation may be useful in hyperbaric oxygen inhalation and not useful under local tissue hypoxia induced by tourniquet application. Reoxygenation occurs with shrinkage of tumor after irradiation and this phenomenon will diminish the value of hyperbaric oxygen in radiation therapy. (author)

Radiation survival of cells from spheroids grown in different oxygen concentrations

International Nuclear Information System (INIS)

Franko, A.J.; Sutherland, R.M.

1979-01-01

The position of the internal, chronically hypoxic cells in spheroids was varied by alterations in the oxygen concentration in the growth medium. Such alterations were expected to cause large changes in the size of the radiobiologically hypoxic fraction. This was tested by growing and irradiating spheroids in oxygen concentrations between 5 and 20.3%, ensuring that the irradiation and growth conditions were as similar as possible. The survival curves appeared to be linear below a surviving fraction of 3 x 10 -2 , and the slopes were intermediate between the slopes of control curves for cells from spheroids irradiated in nitrogen or when fully oxygenated. Thus direct estimates of the hypoxic fractions could not be made. Two models of oxygen diffusion might explain the data. One model assumes that a large fraction of cells was fully hypoxic (radiobiologically) and that these internal, G 1 -confined, chronically hypoxic cells had a lower inherent radioresistance than the outer proliferating cells. Evidence was presented which indicated that this model was unlikely to be correct. The other model assumes that the inherent radioresistance was equal throughout the spheroid, and that the innermost cells died before the oxygen concentration was reduced sufficiently to cause full hypoxic protection. Theoretical survival curves based on this model were generated using the measured geometries ofthe spheroids and multitarget single-hit survival theory. Acceptable agreement with the postulate that the innermost cells of spheroids die at between 0.2 and 0.4% oxygen was obtained. These data may have implications regarding the relative contributions of chronic and acute hypoxia to the fraction of hypoxic cells in tumors

Physiological responses to acute experimental hypoxia in the air ...

Indian Academy of Sciences (India)

When C. batrachus was exposed for different periods at experimental hypoxia level (0.98±0.1 mg/L, DO), hemoglobin and hematocrit concentrations were increased, along with decrease in mean cellular hemoglobin concentration, which reflected a physiological adaptation to enhance oxygen transport capacity. Significant ...

Overexpression of Dimethylarginine Dimethylaminohydrolase Enhances Tumor Hypoxia: An Insight into the Relationship of Hypoxia and Angiogenesis In Vivo

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Vassiliki Kostourou

2004-07-01

Full Text Available The oxygenation status of tumors derived from wild-type C6 glioma cells and clone D27 cells overexpressing dimethylarginine dimethylaminohydrolase (DDAH was assessed in vivo using a variety of direct and indirect assays of hypoxia. Clone D27 tumors exhibit a more aggressive and better-vascularized phenotype compared to wild-type C6 gliomas. Immunohistochemical analyses using the 2-nitroimidazole hypoxia marker pimonidazole, fiber optic OxyLite measurements of tumor pO2, and localized 31P magnetic resonance spectroscopy measurements of tumor bioenergetic status and pH clearly demonstrated that the D27 tumors were more hypoxic compared to C6 wild type. In the tumor extracts, only glucose concentrations were significantly lower in the D27 tumors. Elevated Glut-1 expression, a reliable functional marker for hypoxia-inducible factor-1-mediated metabolic adaptation, was observed in the D27 tumors. Together, the data show that overexpression of DDAH results in C6 gliomas that are more hypoxic compared to wild-type tumors, and point strongly to an inverse relationship of tumor oxygenation and angiogenesis in vivo-a concept now being supported by the enhanced understanding of oxygen sensing at the molecular level.

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for SEAMAP Cruises of 2001 - 2016

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National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana-Florida continental shelf...

Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results

Energy Technology Data Exchange (ETDEWEB)

Wedegaertner, U.; Adam, G. [Abt. fuer Diagnostische und Interventionelle Radiologie, Klinik und Poliklinik fuer Radiologie, UKE Hamburg (Germany); Tchirikov, M.; Schroeder, H. [Abt. fuer experimentelle Gynaekologie der Universitaetsfrauenklinik, Klinik und Poliklinik fuer Frauenheilkunde, UKE, Hamburg (Germany); Koch, M. [Klinik und Poliklinik fuer Neurologie, UKE Hamburg (Germany)

2002-06-01

Purpose: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. Material and Methods: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N{sub 2}O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. Results: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ({proportional_to}40%) from control than in the fetal brain ({proportional_to}10%). Conclusions: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow. (orig.) [German] Ziel: Untersuchung des Potentiales der funktionellen MRT (BOLD) in der Darstellung von Veraenderungen in der Sauerstoffsaettigung fetaler Gewebe waehrend akuter materner Hypoxie bei fetalen Laemmern. Material und Methoden: Die MR-Untersuchung wurde an zwei Mutterschafen mit 125 und 131 Tage alten Feten in Inhalationsnarkose durchgefuehrt. Die BOLD Messungen von fetaler Leber, Myokard und Gehirn erfolgten waehrend einer akuten Hypoxiephase des Muttertieres, in der Sauerstoff durch N{sub 2}O ersetzt wurde. Die materne Sauerstoffsaettigung und Herzfrequenz wurde durch ein Pulsoxymeter ueberwacht. Ergebnisse: Aenderungen der fetalen Gewebsoxygenierung waehrend einer akuten Hypoxiephase der Mutter waren mit der BOLD-MR-Bildgebung deutlich darstellbar. In der fetalen Leber und dem Myokard zeigte sich ein staerkerer Signalabfall um ca. 40% von den Kontrollwerten als im fetalen

Oxygen status during haemodialysis. The Cord-Group

DEFF Research Database (Denmark)

Nielsen, A L; Jensen, H Æ; Hegbrant, J

1995-01-01

Hypoxia during haemodialysis, mainly acetate, has been reported several times. In our study we have monitored oxygen status during 258 bicarbonate haemodialyses. A significant drop below 80 mmHg in mean oxygen tension occurred. Mean oxygen saturation reflected this drop but did not reach levels...... below 90%. The mean oxygen concentration was on the whole critical low, though slightly increasing during each haemodialysis session due to ultrafiltration. It is concluded that both hypoxia and hypoxaemia do occur during bicarbonate haemodialysis. To a group of patients generally having limited cardiac...... reserves, a poor oxygen status is a potentially serious complication to haemodialysis. Monitoring oxygen status is thus advisable....

Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function

Science.gov (United States)

McNamee, Eóin N.; Johnson, Darlynn Korns; Homann, Dirk

2014-01-01

Oxygen is a molecule that is central to cellular respiration and viability, yet there are multiple physiologic and pathological contexts in which cells experience conditions of insufficient oxygen availability, a state known as hypoxia. Given the metabolic challenges of a low oxygen environment, hypoxia elicits a range of adaptive responses at the cellular, tissue, and systemic level to promote continued survival and function. Within this context, T lymphocytes are a highly migratory cell type of the adaptive immune system that frequently encounters a wide range of oxygen tensions in both health and disease. It is now clear that oxygen availability regulates T cell differentiation and function, a response orchestrated in large part by the hypoxia-inducible factor transcription factors. Here, we discuss the physiologic scope of hypoxia and hypoxic signaling, the contribution of these pathways in regulating T cell biology, and current gaps in our understanding. Finally, we discuss how emerging therapies that modulate the hypoxic response may offer new modalities to alter T cell function and the outcome of acute and chronic pathologies. PMID:22961658

Cyclosporine treatment reduces oxygen free radical generation and oxidative stress in the brain of hypoxia-reoxygenated newborn piglets.

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Richdeep S Gill

Full Text Available Oxygen free radicals have been implicated in the pathogenesis of hypoxic-ischemic encephalopathy. It has previously been shown in traumatic brain injury animal models that treatment with cyclosporine reduces brain injury. However, the potential neuroprotective effect of cyclosporine in asphyxiated neonates has yet to be fully studied. Using an acute newborn swine model of hypoxia-reoxygenation, we evaluated the effects of cyclosporine on the brain, focusing on hydrogen peroxide (H(2O(2 production and markers of oxidative stress. Piglets (1-4 d, 1.4-2.5 kg were block-randomized into three hypoxia-reoxygenation experimental groups (2 h hypoxia followed by 4 h reoxygenation (n = 8/group. At 5 min after reoxygenation, piglets were given either i.v. saline (placebo, controls or cyclosporine (2.5 or 10 mg/kg i.v. bolus in a blinded-randomized fashion. An additional sham-operated group (n = 4 underwent no hypoxia-reoxygenation. Systemic hemodynamics, carotid arterial blood flow (transit-time ultrasonic probe, cerebral cortical H(2O(2 production (electrochemical sensor, cerebral tissue glutathione (ELISA and cytosolic cytochrome-c (western blot levels were examined. Hypoxic piglets had cardiogenic shock (cardiac output 40-48% of baseline, hypotension (mean arterial pressure 27-31 mmHg and acidosis (pH 7.04 at the end of 2 h of hypoxia. Post-resuscitation cyclosporine treatment, particularly the higher dose (10 mg/kg, significantly attenuated the increase in cortical H(2O(2 concentration during reoxygenation, and was associated with lower cerebral oxidized glutathione levels. Furthermore, cyclosporine treatment significantly attenuated the increase in cortical cytochrome-c and lactate levels. Carotid blood arterial flow was similar among groups during reoxygenation. Conclusively, post-resuscitation administration of cyclosporine significantly attenuates H(2O(2 production and minimizes oxidative stress in newborn piglets following hypoxia-reoxygenation.

Signaling hypoxia by hypoxia-inducible factor protein hydroxylases: a historical overview and future perspectives

Science.gov (United States)

Bishop, Tammie; Ratcliffe, Peter J

2014-01-01

By the early 1900s, the close matching of oxygen supply with demand was recognized to be a fundamental requirement for physiological function, and multiple adaptive responses to environment hypoxia had been described. Nevertheless, the widespread operation of mechanisms that directly sense and respond to levels of oxygen in animal cells was not appreciated for most of the twentieth century with investigators generally stressing the regulatory importance of metabolic products. Work over the last 25 years has overturned that paradigm. It has revealed the existence of a set of “oxygen-sensing” 2-oxoglutarate dependent dioxygenases that catalyze the hydroxylation of specific amino acid residues and thereby control the stability and activity of hypoxia-inducible factor. The hypoxia-inducible factor hydroxylase pathway regulates a massive transcriptional cascade that is operative in essentially all animal cells. It transduces a wide range of responses to hypoxia, extending well beyond the classical boundaries of hypoxia physiology. Here we review the discovery and elucidation of these pathways, and consider the opportunities and challenges that have been brought into focus by the findings, including new implications for the integrated physiology of hypoxia and therapeutic approaches to ischemic/hypoxic disease. PMID:27774477

Induction of gastrin expression in gastrointestinal cells by hypoxia or cobalt is independent of hypoxia-inducible factor (HIF).

Science.gov (United States)

Xiao, Lin; Kovac, Suzana; Chang, Mike; Shulkes, Arthur; Baldwin, Graham S; Patel, Oneel

2012-07-01

Gastrin and its precursors have been shown to promote mitogenesis and angiogenesis in gastrointestinal tumors. Hypoxia stimulates tumor growth, but its effect on gastrin gene regulation has not been examined in detail. Here we have investigated the effect of hypoxia on the transcription of the gastrin gene in human gastric cancer (AGS) cells. Gastrin mRNA was measured by real-time PCR, gastrin peptides were measured by RIA, and gastrin promoter activity was measured by dual-luciferase reporter assay. Exposure to a low oxygen concentration (1%) increased gastrin mRNA concentrations in wild-type AGS cells (AGS) and in AGS cells overexpressing the gastrin receptor (AGS-cholecystokinin receptor 2) by 2.1 ± 0.4- and 4.1 ± 0.3-fold (P factor hypoxia-inducible factor 1 (HIF-1) or knockdown of either the HIF-1α or HIF-1β subunit did not affect gastrin promoter inducibility under hypoxia indicated that the hypoxic activation of the gastrin gene is likely HIF independent. Mutational analysis of previously identified Sp1 regulatory elements in the gastrin promoter also failed to abrogate the induction of promoter activity by hypoxia. The observations that hypoxia up-regulates the gastrin gene in AGS cells by HIF-independent mechanisms, and that this effect is enhanced by the presence of gastrin receptors, provide potential targets for gastrointestinal cancer therapy.

Respiratory adaptations in carp blood. Influences of hypoxia, red cell organic phosphates, divalent cations and CO2 on hemoglobin-oxygen affinity

DEFF Research Database (Denmark)

Weber, Roy E.; Lykkeboe, G.

1978-01-01

This study concerns the adaptation of oxygen transporting function of carp blood to environment hypoxia, tracing the roles played by erythrocytic cofactors, inorganic cations, carbon dioxide and hemoglobin multiplicity. Carp acclimated to hypoxia ( 30 mmHg) display striking increases in blood oxy...

Vitamin E supplementation inhibits muscle damage and inflammation after moderate exercise in hypoxia.

Science.gov (United States)

Santos, S A; Silva, E T; Caris, A V; Lira, F S; Tufik, S; Dos Santos, R V T

2016-08-01

Exercise under hypoxic conditions represents an additional stress in relation to exercise in normoxia. Hypoxia induces oxidative stress and inflammation as mediated through tumour necrosis factor (TNF)-α release that might be exacerbated through exercise. In addition, vitamin E supplementation might attenuate oxidative stress and inflammation resulting from hypoxia during exercise. The present study aimed to evaluate the effects of vitamin E supplementation (250 mg) on inflammatory parameters and cellular damage after exercise under hypoxia simulating an altitude of 4200 m. Nine volunteers performed three sessions of 60 min of exercise (70% maximal oxygen uptake) interspersed for 1 week under normoxia, hypoxia and hypoxia after vitamin E supplementation 1 h before exercise. Blood was collected before, immediately after and at 1 h after exercise to measure inflammatory parameters and cell damage. Percentage oxygen saturation of haemoglobin decreased after exercise and recovered 1 h later in the hypoxia + vitamin condition (P exercise (P exercise in hypoxia increased interleukin (IL)-6, TNF-α, IL-1ra and IL-10 immediately after exercise (P exercise in hypoxia without supplementation (P exercise reduces cell damage markers after exercise in hypoxia and changes the concentration of cytokines, suggesting a possible protective effect against inflammation induced by hypoxia during exercise. © 2016 The British Dietetic Association Ltd.

Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics.

Science.gov (United States)

Scandurra, Francesca M; Gnaiger, Erich

2010-01-01

When oxygen supply to tissues is limiting, mitochondrial respiration and ATP production are compromised. To assess the bioenergetic consequences under normoxia and hypoxia, quantitative evaluation of mitochondrial oxygen kinetics is required. Using high-resolution respirometry, the "apparent K (m)" for oxygen or p (50) of respiration in 32D cells was determined at 0.05 +/- 0.01 kPa (0.4 mmHg, 0.5 microM, 0.25% air saturation). Close agreement with p (50) of isolated mitochondria indicates that intracellular gradients are small in small cells at routine activity. At intracellular p (O2) respiration is limited by >2% with a p (50) of 0.05 kPa. Over-estimation of p (50) at 0.4 kPa (3 mmHg) would imply significant (>17%) oxygen limitation of respiration under intracellular normoxia. Based on a critical review, we conclude that p (50) ranges from 0.01 to 0.10 kPa in mitochondria and small cells in the absence of inhibitors of cytochrome c oxidase, whereas experimental artefacts explain the controversial >200-fold range of p (50) in the literature on mitochondrial oxygen kinetics.

The Clinical Importance of Assessing Tumor Hypoxia: Relationship of Tumor Hypoxia to Prognosis and Therapeutic Opportunities

Science.gov (United States)

Walsh, Joseph C.; Lebedev, Artem; Aten, Edward; Madsen, Kathleen; Marciano, Liane

2014-01-01

I. Introduction II. The Clinical Importance of Tumor Hypoxia A. Pathophysiology of hypoxia B. Hypoxia's negative impact on the effectiveness of curative treatment 1. Hypoxic tumors accumulate and propagate cancer stem cells 2. Hypoxia reduces the effectiveness of radiotherapy 3. Hypoxia increases metastasis risk and reduces the effectiveness of surgery 4. Hypoxic tumors are resistant to the effects of chemotherapy and chemoradiation C. Hypoxia is prognostic for poor patient outcomes III. Diagnosis of Tumor Hypoxia A. Direct methods 1. Oxygen electrode—direct pO2 measurement most used in cancer research 2. Phosphorescence quenching—alternative direct pO2 measurement 3. Electron paramagnetic resonance 4. 19F-magnetic resonance spectroscopy 5. Overhauser-enhanced MRI B. Endogenous markers of hypoxia 1. Hypoxia-inducible factor-1α 2. Carbonic anhydrase IX 3. Glucose transporter 1 4. Osteopontin 5. A combined IHC panel of protein markers for hypoxia 6. Comet assay C. Physiologic methods 1. Near-infrared spectroscopy/tomography—widely used for pulse oximetry 2. Photoacoustic tomography 3. Contrast-enhanced color duplex sonography 4. MRI-based measurements 5. Blood oxygen level-dependent MRI 6. Pimonidazole 7. EF5 (pentafluorinated etanidazole) 8. Hypoxia PET imaging—physiologic hypoxia measurement providing tomographic information a. 18F-fluoromisonidazole b. 18F-fluoroazomycinarabinofuranoside c. 18F-EF5 (pentafluorinated etanidazole) d. 18F-flortanidazole e. Copper (II) (diacetyl-bis (N4-methylthiosemicarbazone)) f. 18F-FDG imaging of hypoxia IV. Modifying Hypoxia to Improve Therapeutic Outcomes A. Use of hypoxia information in radiation therapy planning B. Use of hypoxia assessment for selection of patients responsive to nimorazole C. Use of hypoxia assessment for selection of patients responsive to tirapazamine D. Use of hypoxia assessment for selection of patients

Pericellular oxygen monitoring with integrated sensor chips for reproducible cell culture experiments.

Science.gov (United States)

Kieninger, J; Aravindalochanan, K; Sandvik, J A; Pettersen, E O; Urban, G A

2014-04-01

Here we present an application, in two tumour cell lines, based on the Sensing Cell Culture Flask system as a cell culture monitoring tool for pericellular oxygen sensing. T-47D (human breast cancer) and T98G (human brain cancer) cells were cultured either in atmospheric air or in a glove-box set at 4% oxygen, in both cases with 5% CO2 in the gas phase. Pericellular oxygen tension was measured with the help of an integrated sensor chip comprising oxygen sensor arrays. Obtained results illustrate variation of pericellular oxygen tension in attached cells covered by stagnant medium. Independent of incubation conditions, low pericellular oxygen concentration levels, usually associated with hypoxia, were found in dense cell cultures. Respiration alone brought pericellular oxygen concentration down to levels which could activate hypoxia-sensing regulatory processes in cultures believed to be aerobic. Cells in culture believed to experience conditions of mild hypoxia may, in reality, experience severe hypoxia. This would lead to incorrect assumptions and suggests that pericellular oxygen concentration readings are of great importance to obtain reproducible results when dealing with hypoxic and normoxic (aerobic) incubation conditions. The Sensing Cell Culture Flask system allows continuous monitoring of pericellular oxygen concentration with outstanding long-term stability and no need for recalibration during cell culture experiments. The sensor is integrated into the flask bottom, thus in direct contact with attached cells. No additional equipment needs to be inserted into the flask during culturing. Transparency of the electrochemical sensor chip allows optical inspection of cells attached on top of the sensor. © 2014 John Wiley & Sons Ltd.

Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells.

Science.gov (United States)

Seno, Kotomi; Tanikawa, Nao; Takahashi, Hironori; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito; Shirasuna, Koumei

2018-02-15

We investigated the effect of oxygen concentrations on cellular senescence and autophagy and examined the role of autophagy in human trophoblast cells. Human first-trimester trophoblast cells (Sw.71) were incubated under 21%, 5%, or 1% O 2 concentrations for 24 hours. We examined the extent of senescence caused using senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated secretory phenotype (SASP) as markers. Moreover, we examined the role of autophagy in causing cellular senescence using an autophagy inhibitor (3-methyladenine, 3MA). Physiological normoxia (5% O 2 ) decreased SA-β-Gal-positive cells and SASP including interleukin-6 (IL-6) and IL-8 compared with cultured cells in 21% O 2 . Pathophysiological hypoxia (1% O 2 ) caused cytotoxicity, including extracellular release of ATP and lactate dehydrogenase, and decreased senescence phenotypes. 3MA-treated trophoblast cells significantly suppressed senescence markers (SA-β-Gal-positive cells and SASP secretion) in O 2 -independent manner. We conclude that O 2 concentration modulates cellular senescence phenotypes regulating autophagy in the human trophoblast cells. Moreover, inhibiting autophagy suppresses cellular senescence, suggesting that autophagy contributes to oxygen stress-induced cellular senescence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuroepithelial cells and the hypoxia emersion response in the amphibious fish Kryptolebias marmoratus.

Science.gov (United States)

Regan, Kelly S; Jonz, Michael G; Wright, Patricia A

2011-08-01

Teleost fish have oxygen-sensitive neuroepithelial cells (NECs) in the gills that appear to mediate physiological responses to hypoxia, but little is known about oxygen sensing in amphibious fish. The mangrove rivulus, Kryptolebias marmoratus, is an amphibious fish that respires via the gills and/or the skin. First, we hypothesized that both the skin and gills are sites of oxygen sensing in K. marmoratus. Serotonin-positive NECs were abundant in both gills and skin, as determined by immunohistochemical labelling and fluorescence microscopy. NECs retained synaptic vesicles and were found near nerve fibres labelled with the neuronal marker zn-12. Skin NECs were 42% larger than those of the gill, as estimated by measurement of projection area, and 45% greater in number. Moreover, for both skin and gill NECs, NEC area increased significantly (30-60%) following 7 days of exposure to hypoxia (1.5 mg l(-1) dissolved oxygen). Another population of cells containing vesicular acetylcholine transporter (VAChT) proteins were also observed in the skin and gills. The second hypothesis we tested was that K. marmoratus emerse in order to breathe air cutaneously when challenged with severe aquatic hypoxia, and this response will be modulated by neurochemicals associated chemoreceptor activity. Acute exposure to hypoxia induced fish to emerse at 0.2 mg l(-1). When K. marmoratus were pre-exposed to serotonin or acetylcholine, they emersed at a significantly higher concentration of oxygen than untreated fish. Pre-exposure to receptor antagonists (ketanserin and hexamethonium) predictably resulted in fish emersing at a lower concentration of oxygen. Taken together, these results suggest that oxygen sensing occurs at the branchial and/or cutaneous surfaces in K. marmoratus and that serotonin and acetylcholine mediate, in part, the emersion response.

Analysis of hypoxia and hypoxia-like states through metabolite profiling.

Directory of Open Access Journals (Sweden)

Julie E Gleason

Full Text Available In diverse organisms, adaptation to low oxygen (hypoxia is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress.

Hypoxia/reoxygenation increases the permeability of endothelial cell monolayers: Role of oxygen radicals

International Nuclear Information System (INIS)

Inauen, W.; Payne, D.K.; Kvietys, P.R.; Granger, D.N.

1990-01-01

We assessed the effect of hypoxia/reoxygenation on 14C-albumin flux across endothelial monolayers. Cultured bovine pulmonary artery endothelial cells were grown to confluence on nitrocellulose filters (pore size 12 microns). The endothelialized filters were mounted in Ussing-type chambers which were filled with cell culture medium (M 199). Equimolar amounts (33 nM) of 14C-labeled and unlabeled albumin were added to the hot and cold chambers, respectively. The monolayers were then exposed to successive periods (90 min) of normoxia (pO2 145 mmHg), hypoxia (pO2 20 mmHg), and reoxygenation (pO2 145 mmHg). A gas bubbling system was used to control media pO2 and to ensure adequate mixing. Four aliquots of culture media were taken during each period in order to calculate the 14C-albumin permeability across the endothelialized filter. In some experiments, either the xanthine oxidase inhibitor, oxypurinol (10 microM), or superoxide dismutase (600 U/mL), was added to the media immediately prior to the experiments. As compared to the normoxic control period, albumin permeability was 1.5 times higher during hypoxia (p less than 0.01) and 2.3 times higher during reoxygenation (p less than 0.01). The reoxygenation-induced increase in albumin permeability was prevented by either oxypurinol or superoxide dismutase. These data indicate that xanthine oxidase-derived oxygen radicals contribute to the hypoxia/reoxygenation-induced endothelial cell dysfunction. The altered endothelial barrier function induced by hypoxia/reoxygenation is consistent with the microvascular dysfunction observed following reperfusion of ischemic tissues

Complex Evaluation Oxygen Status and Lipid Metabolism Indexes in Newborns with Perinatal Hypoxia and Hypovolemic Shock

Directory of Open Access Journals (Sweden)

Svetlana A. Perepelitsa

2017-01-01

Full Text Available Aim. To asses of metabolism, lipid metabolism and oxygen status parameters in newborns with perinatal hypoxia.Materials and Methods. 53 newborn babies born with signs of severe hypoxia and low Apgar scoring equal to 2 at the 1st minute of life were enrolled in the study. Newborns were divided into 2 groups depending on the presence of the clinical presentation of shock: Group 1 «Shock» and Group 2 «Acute intranatal hypoxia» (AIH. All newborns underwent testing for blood gas and acid-base balance, lactate level. Cholesterol and triglyceride levels in the central venous blood were also tested immediately after the birth and on the 5th day of life. Mechanical ventilation mode and parameters were registered. The mean airway pressure (MAP and the oxygen saturation index (OSI were calculated.Results. Severe decompensated metabolic lactic acidosis was diagnosed in a «Shock» group newborns at birth, thus indicating severe perinatal hypoxia which had triggered the development of shock. As for the «AIH» group newborns, they had hyperlactatemia alone. The most severe hypoxemia at birth was diagnosed in newborns of the «Shock» group; the OSI value in these infants was significantly higher than that in «AIH» infants (P<0.01. Despite the treatment and mechanical ventilation, during the posthypoxic period, newborns from the «Shock» group were characterized by increased OSI values over 12 hours after birth. Significantly high levels of OSI persisted for 48 hours after the delivery. Severe hypotriglyceridemia and hypocholesterolemia were found in both group newborns.Conclusion. The study demonstrated that there was intranatal complex metabolism impairment in the case of perinatal hypoxia; at birth, it manifested by metabolic acidosis of various degrees of severity and imbalance of triglycerides and cholesterol levels. The longer and more severe hypoxia is, the more severe acid-base balance and blood lactate level impairment at birth become

A Novel, Inexpensive Method to Monitor, Record, and Analyze Breathing Behavior During Normobaric Hypoxia Generated by the Reduced Oxygen Breathing Device.

Science.gov (United States)

Temme, Leonard A; St Onge, Paul; Adams, Mark; Still, David L; Statz, Jonathan K; Williams, Steven T

2017-03-01

Since hypoxia remains one of the most important physiological hazards the aviation environment poses, military aviators are trained to recognize symptoms of hypoxia in order to implement appropriate safety procedures and countermeasures when hypoxia occurs. A widely used commercial instrument for hypoxia training, demonstration, and research is the Reduced Oxygen Breathing Device (ROBD). Here we describe a novel, inexpensive method to use the ROBD's breathing loop pressure (BLP) to measure respiration rate, a critically important response parameter for hypoxia. The ROBD can be controlled by a computer to export several variables including BLP, via the ROBD's RS232 port. An archived database was reanalyzed to assess the BLP data. New instrumentation added independent measures of respiration and expired oxygen and carbon dioxide; these measures were integrated with the ROBD output. Analysis of the archived data showed that the BLP reflected realistic breathing patterns. The new instrumentation integrated well with the ROBD, and independently supported the potential of the BLP as a valid measure of respiration. The ROBD's BLP data may provide a basis for a reliable, sensitive measure of respiration that is available at no additional cost. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

A Pilot Study of Inhaled CO Therapy in Neonatal Hypoxia-Ischemia: Carboxyhemoglobin Concentrations and Brain Volumes.

Science.gov (United States)

Douglas-Escobar, Martha; Mendes, Monique; Rossignol, Candace; Bliznyuk, Nikolay; Faraji, Ariana; Ahmad, Abdullah S; Doré, Sylvain; Weiss, Michael D

2018-01-01

Objective: The objective of this pilot study was to start evaluating the efficacy and the safety (i.e., carboxyhemoglobin concentration of carbon monoxide (CO)) as a putative neuroprotective therapy in neonates. Study Design: Neonatal C57BL/6 mice were exposed to CO at a concentration of either 200 or 250 ppm for a period of 1 h. The pups were then sacrificed at 0, 10, 20, 60, 120, 180, and 240 min after exposure to either concentration of CO, and blood was collected for analysis of carboxyhemoglobin. Following the safety study, 7-day-old pups underwent a unilateral carotid ligation. After recovery, the pups were exposed to a humidified gas mixture of 8% oxygen and 92% nitrogen for 20 min in a hypoxia chamber. One hour after the hypoxia exposure, the pups were randomized to one of two groups: air (HI+A) or carbon monoxide (HI+CO). An inhaled dose of 250 ppm of CO was administered to the pups for 1 h per day for a period of 3 days. At 7 days post-injury, the pups were sacrificed and the brains analyzed for cortical and hippocampal volumes. Results: CO exposure at 200 and 250 ppm produced a peak carboxyhemoglobin concentration of 21.52 ± 1.18% and 27.55 ± 3.58%, respectively. The carboxyhemoglobin concentrations decreased rapidly, reaching control concentrations by 60 min post exposure. At 14 days of age (7 days post injury), the HI+CO (treated with 1 h per day of 250 ppm of CO for 3 days post injury) had significant preservation of the ratio of ipsilateral to contralateral cortex (median 1.07, 25% 0.97, 75% 1.23, n = 10) compared the HI+A group ( p carboxyhemoglobin concentrations which would induce acute neurologic abnormalities and was effective in preserving cortical volumes following hypoxic-ischemic injury.

Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

DEFF Research Database (Denmark)

Klausen, T; Christensen, H; Hansen, J M

1996-01-01

exposed to 2 h each of hypocapnic hypoxia, normocapnic hypoxia, hypocapnic normoxia, and normal breathing of room air (control experiment). During the control experiment, serum-EPO showed significant variations (ANOVA P = 0.047) with a 15% increase in mean values. The serum-EPO measured in the other...... (10% Co2 with 10% O2) to the hypoxic gas mixture. This elicited an increased ventilation, unaltered arterial pH and haemoglobin oxygen affinity, a lower degree of hypoxia than during hypocapnic hypoxia, and no significant changes in serum-EPO (ANOVA P > 0.05). Hypocapnic normoxia, produced...

Hypoxia tolerance in coral-reef triggerfishes (Balistidae)

Science.gov (United States)

Wong, Corrie C.; Drazen, Jeffrey C.; Callan, Chatham K.; Korsmeyer, Keith E.

2018-03-01

Despite high rates of photosynthetic oxygen production during the day, the warm waters of coral reefs are susceptible to hypoxia at night due to elevated respiration rates at higher temperatures that also reduce the solubility of oxygen. Hypoxia may be a challenge for coral-reef fish that hide in the reef to avoid predators at night. Triggerfishes (Balistidae) are found in a variety of reef habitats, but they also are known to find refuge in reef crevices and holes at night, which may expose them to hypoxic conditions. The critical oxygen tension ( P crit) was determined as the point below which oxygen uptake could not be maintained to support standard metabolic rate (SMR) for five species of triggerfish. The triggerfishes exhibited similar levels of hypoxia tolerance as other coral-reef and coastal marine fishes that encounter low oxygen levels in their environment. Two species, Rhinecanthus rectangulus and R. aculeatus, had the lowest P crit ( 3.0 kPa O2), comparable to the most hypoxia-tolerant obligate coral-dwelling gobies, while Odonus niger and Sufflamen bursa were moderately tolerant to hypoxia ( P crit 4.5 kPa), and Xanthichthys auromarginatus was intermediate ( P crit 3.7 kPa). These differences in P crit were not due to differences in oxygen demand, as all the species had a similar SMR once mass differences were taken into account. The results suggest that triggerfish species are adapted for different levels of hypoxia exposure during nocturnal sheltering within the reef.

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia.

Science.gov (United States)

Carreau, Aude; El Hafny-Rahbi, Bouchra; Matejuk, Agata; Grillon, Catherine; Kieda, Claudine

2011-06-01

Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO(2)), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well-organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique 'tissue normoxia' or 'physioxia' status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO(2), i.e. 'hypoxia'. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO(2) values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O(2) whereas current in vitro experimentations are usually performed in 19.95% O(2), an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Combining hypobaric hypoxia or hyperbaric oxygen postconditioning with memantine reduces neuroprotection in 7-day-old rat hypoxia-ischemia.

Science.gov (United States)

Gamdzyk, Marcin; Ziembowicz, Apolonia; Bratek, Ewelina; Salinska, Elzbieta

2016-10-01

Perinatal hypoxia-ischemia causes brain injury in neonates, but a fully successful treatment to prevent changes in the brain has yet to be developed. The aim of this study was to evaluate the effect of combining memantine treatment with HBO (2.5 ATA) or HH (0.47 ATA) on neonatal hypoxia-ischemia brain injury. 7-day old rats were subjected to hypoxia-ischemia (H-I) and treated with combination of memantine and HBO or HH. The brain damage was evaluated by examination of infarct area and the number of apoptotic cells in CA1 region of hippocampus. Additionally, the level of reactive oxygen species (ROS) was measured. Memantine, HBO or HH postconditioning applied at short time (1-6h) after H-I, and repeated for two subsequent days, resulted in significant neuroprotection. The reduction in ipsilateral hemisphere weight deficit and in the size of infarct area was observed 14days after H-I. A reduction in apoptosis and ROS level was also observed. Combining memantine with HBO or HH resulted in a loss of neuroprotection. Our results show that, combining HBO or HH postconditioning with memantine produce no additive increase in the neuroprotective effect. On the contrary, combining the treatments resulted in lower neuroprotection in comparison to the effects of memantine, HBO or HH alone. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2008

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Plankton community respiration, net ecosystem metabolism, and oxygen dynamics on the Louisiana continental shelf: implications for hypoxia

Science.gov (United States)

We conducted a multi-year study of the Louisiana continental shelf (LCS) to better understand the linkages between water column metabolism and the formation of hypoxia (dissolved oxygen respiration rates (WR) were measured on 10 cr...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2003

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2001

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2005

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2015

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2009

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2004

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2007

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2012

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2002

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2010

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2006

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2013

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for June and July SEAMAP Cruise of 2014

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Gulf of Mexico Hypoxia Watch Bottom Dissolved Oxygen Contours for October and November SEAMAP Cruise of 2008

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Effect of oxygen on cardiac differentiation in mouse iPS cells: role of hypoxia inducible factor-1 and Wnt/beta-catenin signaling.

Directory of Open Access Journals (Sweden)

Tanya L Medley

Full Text Available BACKGROUND: Disturbances in oxygen levels have been found to impair cardiac organogenesis. It is known that stem cells and differentiating cells may respond variably to hypoxic conditions, whereby hypoxia may enhance stem cell pluripotency, while differentiation of multiple cell types can be restricted or enhanced under hypoxia. Here we examined whether HIF-1alpha modulated Wnt signaling affected differentiation of iPS cells into beating cardiomyocytes. OBJECTIVE: We investigated whether transient and sustained hypoxia affects differentiation of cardiomyocytes derived from murine induced pluripotent stem (iPS cells, assessed the involvement of HIF-1alpha (hypoxia-inducible factor-1alpha and the canonical Wnt pathway in this process. METHODS: Embryoid bodies (EBs derived from iPS cells were differentiated into cardiomyocytes and were exposed either to 24 h normoxia or transient hypoxia followed by a further 13 days of normoxic culture. RESULTS: At 14 days of differentiation, 59 ± 2% of normoxic EBs were beating, whilst transient hypoxia abolished beating at 14 days and EBs appeared immature. Hypoxia induced a significant increase in Brachyury and islet-1 mRNA expression, together with reduced troponin C expression. Collectively, these data suggest that transient and sustained hypoxia inhibits maturation of differentiating cardiomyocytes. Compared to normoxia, hypoxia increased HIF-1alpha, Wnt target and ligand genes in EBs, as well as accumulation of HIF-1alpha and beta-catenin in nuclear protein extracts, suggesting involvement of the Wnt/beta-catenin pathway. CONCLUSION: Hypoxia impairs cardiomyocyte differentiation and activates Wnt signaling in undifferentiated iPS cells. Taken together the study suggests that oxygenation levels play a critical role in cardiomyocyte differentiation and suggest that hypoxia may play a role in early cardiogenesis.

Effect of hypoxia on cerebral blood flow regulation during rest and exercise : role of cerebral oxygen delivery on performance

OpenAIRE

Fan, J.-L.

2014-01-01

Adequate supply of oxygen to the brain is critical for maintaining normal brain function. Severe hypoxia, such as that experienced during high altitude ascent, presents a unique challenge to brain oxygen (O2) supply. During high-intensity exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, followed by reductions in cerebral blood flow (CBF), oxygen delivery (DO2), and tissue oxygenation. This reduced O2 supply to the brain could potentially account for the reduce...

A Lab Assembled Microcontroller-Based Sensor Module for Continuous Oxygen Measurement in Portable Hypoxia Chambers

Science.gov (United States)

Mathupala, Saroj P.; Kiousis, Sam; Szerlip, Nicholas J.

2016-01-01

Background Hypoxia-based cell culture experiments are routine and essential components of in vitro cancer research. Most laboratories use low-cost portable modular chambers to achieve hypoxic conditions for cell cultures, where the sealed chambers are purged with a gas mixture of preset O2 concentration. Studies are conducted under the assumption that hypoxia remains unaltered throughout the 48 to 72 hour duration of such experiments. Since these chambers lack any sensor or detection system to monitor gas-phase O2, the cell-based data tend to be non-uniform due to the ad hoc nature of the experimental setup. Methodology With the availability of low-cost open-source microcontroller-based electronic project kits, it is now possible for researchers to program these with easy-to-use software, link them to sensors, and place them in basic scientific apparatus to monitor and record experimental parameters. We report here the design and construction of a small-footprint kit for continuous measurement and recording of O2 concentration in modular hypoxia chambers. The low-cost assembly (US$135) consists of an Arduino-based microcontroller, data-logging freeware, and a factory pre-calibrated miniature O2 sensor. A small, intuitive software program was written by the authors to control the data input and output. The basic nature of the kit will enable any student in biology with minimal experience in hobby-electronics to assemble the system and edit the program parameters to suit individual experimental conditions. Results/Conclusions We show the kit’s utility and stability of data output via a series of hypoxia experiments. The studies also demonstrated the critical need to monitor and adjust gas-phase O2 concentration during hypoxia-based experiments to prevent experimental errors or failure due to partial loss of hypoxia. Thus, incorporating the sensor-microcontroller module to a portable hypoxia chamber provides a researcher a capability that was previously available

A Lab Assembled Microcontroller-Based Sensor Module for Continuous Oxygen Measurement in Portable Hypoxia Chambers.

Directory of Open Access Journals (Sweden)

Saroj P Mathupala

Full Text Available Hypoxia-based cell culture experiments are routine and essential components of in vitro cancer research. Most laboratories use low-cost portable modular chambers to achieve hypoxic conditions for cell cultures, where the sealed chambers are purged with a gas mixture of preset O2 concentration. Studies are conducted under the assumption that hypoxia remains unaltered throughout the 48 to 72 hour duration of such experiments. Since these chambers lack any sensor or detection system to monitor gas-phase O2, the cell-based data tend to be non-uniform due to the ad hoc nature of the experimental setup.With the availability of low-cost open-source microcontroller-based electronic project kits, it is now possible for researchers to program these with easy-to-use software, link them to sensors, and place them in basic scientific apparatus to monitor and record experimental parameters. We report here the design and construction of a small-footprint kit for continuous measurement and recording of O2 concentration in modular hypoxia chambers. The low-cost assembly (US$135 consists of an Arduino-based microcontroller, data-logging freeware, and a factory pre-calibrated miniature O2 sensor. A small, intuitive software program was written by the authors to control the data input and output. The basic nature of the kit will enable any student in biology with minimal experience in hobby-electronics to assemble the system and edit the program parameters to suit individual experimental conditions.We show the kit's utility and stability of data output via a series of hypoxia experiments. The studies also demonstrated the critical need to monitor and adjust gas-phase O2 concentration during hypoxia-based experiments to prevent experimental errors or failure due to partial loss of hypoxia. Thus, incorporating the sensor-microcontroller module to a portable hypoxia chamber provides a researcher a capability that was previously available only to labs with access to

A Lab Assembled Microcontroller-Based Sensor Module for Continuous Oxygen Measurement in Portable Hypoxia Chambers.

Science.gov (United States)

Mathupala, Saroj P; Kiousis, Sam; Szerlip, Nicholas J

2016-01-01

Hypoxia-based cell culture experiments are routine and essential components of in vitro cancer research. Most laboratories use low-cost portable modular chambers to achieve hypoxic conditions for cell cultures, where the sealed chambers are purged with a gas mixture of preset O2 concentration. Studies are conducted under the assumption that hypoxia remains unaltered throughout the 48 to 72 hour duration of such experiments. Since these chambers lack any sensor or detection system to monitor gas-phase O2, the cell-based data tend to be non-uniform due to the ad hoc nature of the experimental setup. With the availability of low-cost open-source microcontroller-based electronic project kits, it is now possible for researchers to program these with easy-to-use software, link them to sensors, and place them in basic scientific apparatus to monitor and record experimental parameters. We report here the design and construction of a small-footprint kit for continuous measurement and recording of O2 concentration in modular hypoxia chambers. The low-cost assembly (US$135) consists of an Arduino-based microcontroller, data-logging freeware, and a factory pre-calibrated miniature O2 sensor. A small, intuitive software program was written by the authors to control the data input and output. The basic nature of the kit will enable any student in biology with minimal experience in hobby-electronics to assemble the system and edit the program parameters to suit individual experimental conditions. We show the kit's utility and stability of data output via a series of hypoxia experiments. The studies also demonstrated the critical need to monitor and adjust gas-phase O2 concentration during hypoxia-based experiments to prevent experimental errors or failure due to partial loss of hypoxia. Thus, incorporating the sensor-microcontroller module to a portable hypoxia chamber provides a researcher a capability that was previously available only to labs with access to sophisticated (and

Biochemical and hematological responses of the banded knife fish Gymnotus carapo (Linnaeus, 1758 exposed to environmental hypoxia

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G. MORAES

Full Text Available Oxygen of tropical freshwater environments fluctuates drastically. Eutrophic lakes and ponds of warm waters frequently reach very low oxygen concentrations. This is the most common habitat of the banded knife fish "tuvira" Gymnotus carapo. This electric fish is reported to present bimodal breathing to cope with low environmental oxygen. Biochemical responses can be also observed in fishes facing hypoxia but none were studied in tuvira. In the present study, haematological and metabolic changes were investigated in two groups of fish exposed to hypoxia for 1 and 3 hours. Haematocrit, red blood cells and haemoglobin concentration indicated erythrocyte release from hematopoietic organs and swelling of red blood cells. Glycogen, glucose, lactate, pyruvate, and amino acids were quantified in liver, kidney and white muscle. The metabolic profile of G. carapo to cope with hypoxia suggested liver gluconeogenesis probably supported by proteolysis. The kidney and liver presented the same biochemical trend suggesting similar metabolic role for both organs. Glucogenolysis followed by glucose fermentation and protein mobilisation was observed in the white muscle. The air breathing behaviour of tuvira works in parallel with metabolism to prevent damages from hypoxia. Metabolic adjustments are observed when the air taking is avoided.

Biochemical and hematological responses of the banded knife fish Gymnotus carapo (Linnaeus, 1758 exposed to environmental hypoxia

Directory of Open Access Journals (Sweden)

MORAES G.

2002-01-01

Full Text Available Oxygen of tropical freshwater environments fluctuates drastically. Eutrophic lakes and ponds of warm waters frequently reach very low oxygen concentrations. This is the most common habitat of the banded knife fish "tuvira" Gymnotus carapo. This electric fish is reported to present bimodal breathing to cope with low environmental oxygen. Biochemical responses can be also observed in fishes facing hypoxia but none were studied in tuvira. In the present study, haematological and metabolic changes were investigated in two groups of fish exposed to hypoxia for 1 and 3 hours. Haematocrit, red blood cells and haemoglobin concentration indicated erythrocyte release from hematopoietic organs and swelling of red blood cells. Glycogen, glucose, lactate, pyruvate, and amino acids were quantified in liver, kidney and white muscle. The metabolic profile of G. carapo to cope with hypoxia suggested liver gluconeogenesis probably supported by proteolysis. The kidney and liver presented the same biochemical trend suggesting similar metabolic role for both organs. Glucogenolysis followed by glucose fermentation and protein mobilisation was observed in the white muscle. The air breathing behaviour of tuvira works in parallel with metabolism to prevent damages from hypoxia. Metabolic adjustments are observed when the air taking is avoided.

Oxygen effect and intracellular oxygen content (adaptation hypothesis)

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Yarmonenko, S P; Ehpshtejn, I M [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Tsentr

1977-01-01

Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation.

Oxygen effect and intracellular oxygen content (adaptation hypothesis)

International Nuclear Information System (INIS)

Yarmonenko, S.P.; Ehpshtejn, I.M.

1977-01-01

Experimental data indicating that a radiomodifying action of hypoxia is dependent on the ''prehistory'' of the irradiated object are considered. This dependence manifests itself in a decreased protective action of acute hypoxia on the hypoxia-adapted objects. To explain this a hypothesis is proposed connecting a degree of cell radiosensitivity modification, determined by the oxygen effect, with the intracellular oxygen content. The latter, in accord with current ideas, is regulated by variations in the diffusion resistance to oxygen shown by the cytoplasmic membranes depending on the energy level of the cell and the degree of its oxygenation

Network-based association of hypoxia-responsive genes with cardiovascular diseases

International Nuclear Information System (INIS)

Wang, Rui-Sheng; Oldham, William M; Loscalzo, Joseph

2014-01-01

Molecular oxygen is indispensable for cellular viability and function. Hypoxia is a stress condition in which oxygen demand exceeds supply. Low cellular oxygen content induces a number of molecular changes to activate regulatory pathways responsible for increasing the oxygen supply and optimizing cellular metabolism under limited oxygen conditions. Hypoxia plays critical roles in the pathobiology of many diseases, such as cancer, heart failure, myocardial ischemia, stroke, and chronic lung diseases. Although the complicated associations between hypoxia and cardiovascular (and cerebrovascular) diseases (CVD) have been recognized for some time, there are few studies that investigate their biological link from a systems biology perspective. In this study, we integrate hypoxia genes, CVD genes, and the human protein interactome in order to explore the relationship between hypoxia and cardiovascular diseases at a systems level. We show that hypoxia genes are much closer to CVD genes in the human protein interactome than that expected by chance. We also find that hypoxia genes play significant bridging roles in connecting different cardiovascular diseases. We construct a hypoxia-CVD bipartite network and find several interesting hypoxia-CVD modules with significant gene ontology similarity. Finally, we show that hypoxia genes tend to have more CVD interactors in the human interactome than in random networks of matching topology. Based on these observations, we can predict novel genes that may be associated with CVD. This network-based association study gives us a broad view of the relationships between hypoxia and cardiovascular diseases and provides new insights into the role of hypoxia in cardiovascular biology. (paper)

Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.

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Schiffer, Tomas A; Friederich-Persson, Malou

2017-01-01

The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.

The amphibious fish Kryptolebias marmoratus uses different strategies to maintain oxygen delivery during aquatic hypoxia and air exposure.

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Turko, Andy J; Robertson, Cayleih E; Bianchini, Kristin; Freeman, Megan; Wright, Patricia A

2014-11-15

Despite the abundance of oxygen in atmospheric air relative to water, the initial loss of respiratory surface area and accumulation of carbon dioxide in the blood of amphibious fishes during emersion may result in hypoxemia. Given that the ability to respond to low oxygen conditions predates the vertebrate invasion of land, we hypothesized that amphibious fishes maintain O2 uptake and transport while emersed by mounting a co-opted hypoxia response. We acclimated the amphibious fish Kryptolebias marmoratus, which are able to remain active for weeks in both air and water, for 7 days to normoxic brackish water (15‰, ~21kPa O2; control), aquatic hypoxia (~3.6kPa), normoxic air (~21 kPa) or aerial hypoxia (~13.6kPa). Angiogenesis in the skin and bucco-opercular chamber was pronounced in air- versus water-acclimated fish, but not in response to hypoxia. Aquatic hypoxia increased the O2-carrying capacity of blood via a large (40%) increase in red blood cell density and a small increase in the affinity of hemoglobin for O2 (P50 decreased 11%). In contrast, air exposure increased the hemoglobin O2 affinity (decreased P50) by 25% without affecting the number of red blood cells. Acclimation to aerial hypoxia both increased the O2-carrying capacity and decreased the hemoglobin O2 affinity. These results suggest that O2 transport is regulated both by O2 availability and also, independently, by air exposure. The ability of the hematological system to respond to air exposure independent of O2 availability may allow extant amphibious fishes, and may also have allowed primitive tetrapods to cope with the complex challenges of aerial respiration during the invasion of land. © 2014. Published by The Company of Biologists Ltd.

Exercise Improves Mood State in Normobaric Hypoxia.

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Seo, Yongsuk; Fennell, Curtis; Burns, Keith; Pollock, Brandon S; Gunstad, John; McDaniel, John; Glickman, Ellen

2015-11-01

The purpose of this study was to quantify the efficacy of using exercise to alleviate the impairments in mood state associated with hypoxic exposure. Nineteen young, healthy men completed Automated Neuropsychological Assessment Metrics-4(th) Edition (ANAM4) versions of the mood state test before hypoxia exposure, after 60 min of hypoxia exposure (12.5% O(2)), and during and after two intensities of cycling exercise (40% and 60% adjusted Vo(2max)) under the same hypoxic conditions. Peripheral oxygen saturation (Spo(2)) and regional cerebral oxygen saturation (rSo(2)) were continuously monitored. At rest in hypoxia, Total Mood Disturbance (TMD) was significantly increased compared to baseline in both the 40% and 60% groups. TMD was significantly decreased during exercise compared to rest in hypoxia. TMD was also significantly decreased during recovery compared to rest in hypoxia. Spo(2) significantly decreased at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. Regional cerebral oxygen saturation was also reduced at 60 min rest in hypoxia, during exercise, and recovery compared to baseline. The current study demonstrated that exercise at 40% and 60% of adjusted Vo(2max) attenuated the adverse effects of hypoxia on mood. These findings may have significant applied value, as negative mood states are known to impair performance in hypoxia. Further studies are needed to replicate the current finding and to clarify the possible mechanisms associated with the potential benefits of exercise on mood state in normobaric hypoxia.

Hypoxia in the central Arabian Gulf Exclusive Economic Zone (EEZ) of Qatar during summer season

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Al-Ansari, Ebrahim M. A. S.; Rowe, G.; Abdel-Moati, M. A. R.; Yigiterhan, O.; Al-Maslamani, I.; Al-Yafei, M. A.; Al-Shaikh, I.; Upstill-Goddard, R.

2015-06-01

One of the most fascinating and unexpected discoveries during the Qatar University Marine Expeditions to the marine Exclusive Economic Zone (EEZ) of Qatar in 2000-2001, was the detection of a hypoxic water layer in the central region of the Arabian Gulf in waters deeper than 50 m. Hypoxia was defined as the region where the concentration of dissolved oxygen was less than 2 mg L-1. This article presents the discovery of hypoxia in the Arabian Gulf, based on samples collected (mainly during evening or night time) from vertical profiles along transects of the EEZ of Qatar and analyzed for physico-chemical properties, nutrients and chlorophyll-a. Hypoxia occurred in the summer months caused by an interaction between physical stratification of the water column that prevents oxygen replenishment, and biological respiration that consumes oxygen. Strong south-westerly winds (the SW monsoon) from June to September drive the relatively low-salinity nutrient-rich surface water from the Arabian Sea/Arabian Gulf (Sea of Oman) through the Strait of Hormuz into the central-Arabian Gulf, and this surface current penetration fertilizes the deep central-Arabian Gulf during the summer period. A strong seasonal pycnocline is formed between deeper waters at an ambient temperature of 20.9 °C and surface waters at 31.9 °C. This prevents the mixing of supersaturated O2 (>100-130%) water from the upper layer that would otherwise raise concentrations of dissolved oxygen below the thermocline, thus resulting in deep water hypoxia, i.e. dissolved oxygen levels of less than 0.86 ml L-1 at 17.3% saturation. These are the lowest values ever recorded for the Arabian Gulf. The calculated area of hypoxia is around 7220 square kilometers, and occurs in a layer about ≥15 m thick above the sea floor which extends toward the deep part of the Qatar Exclusive Economic Zone (EEZ). The biological consequences of this hypoxia on the sea floor are yet to be investigated.

Association of intraoperative tissue oxygenation with suspected risk factors for tissue hypoxia.

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Spruit, R J; Schwarte, L A; Hakenberg, O W; Scheeren, T W L

2013-10-01

Tissue hypoxia may cause organ dysfunction, but not much is known about tissue oxygenation in the intraoperative setting. We studied microcirculatory tissue oxygen saturation (StO₂) to determine representative values for anesthetized patients undergoing urological surgery and to test the hypothesis that StO₂ is associated with known perioperative risk factors for morbidity and mortality, conventionally monitored variables, and hypotension requiring norepinephrine. Using near-infrared spectroscopy, we measured StO₂ on the thenar eminence in 160 patients undergoing open urological surgery under general anesthesia (FiO2 0.35-0.4), and calculated its correlations with age, risk level for general perioperative complications and mortality (high if age ≥70 and procedure is radical cystectomy), mean arterial pressure (MAP), hemoglobin concentration (Hb), central venous oxygen saturation (ScvO₂), and norepinephrine use. The time averaged StO₂ was 86 ± 6 % (mean ± SD). In the multivariate analysis, Hb [standardized coefficient (SC) 0.21, p = 0.003], ScvO₂ (SC 0.53, p SStO₂ was partly dependent on MAP only when this was below 65 mmHg (lowest MAP SC 0.20, p = 0.006, MAP area under the curve <65 mmHg SC 0.03, p = 0.02). Finally, StO₂ was slightly lower in patients requiring norepinephrine (85 ± 6 vs. 89 ± 6 %, p = 0.001). Intraoperative StO₂ in urological patients was comparable to that of healthy volunteers breathing room air as reported in the literature and correlated with known perioperative risk factors. Further research should investigate its association with outcome and the effect of interventions aimed at optimizing StO₂.

Effects of bottom water oxygen concentrations on mercury distribution and speciation in sediments below the oxygen minimum zone of the Arabian Sea

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Chakraborty, P.; Mason, R.P.; Jayachandran, S.; Vudamala, K.; Armoury, K.; Sarkar, Arindam; Chakraborty, S.; Bardhan, P.; Naik, R.

benthic flux of MeHg to the overlying water (Hollweg et al., 2010; Balcom et al., 2008). On the contrary, however, a study in the Gulf of Mexico did not find that MeHg in bottom waters correlated with the extent of hypoxia (Liu et al., 2015... in the sediments of the so-called “dead zone” in the Gulf of Mexico. Others (Mason et al., 2006; Emili et al., 2011) have shown that total Hg and MeHg fluxes from sediments are enhanced by low oxygen concentrations in the overlying waters. The aim of this study...

Developmental Hypoxia Has Negligible Effects on Long-Term Hypoxia Tolerance and Aerobic Metabolism of Atlantic Salmon (Salmo salar).

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Wood, Andrew T; Clark, Timothy D; Andrewartha, Sarah J; Elliott, Nicholas G; Frappell, Peter B

Exposure to developmental hypoxia can have long-term impacts on the physiological performance of fish because of irreversible plasticity. Wild and captive-reared Atlantic salmon (Salmo salar) can be exposed to hypoxic conditions during development and continue to experience fluctuating oxygen levels as juveniles and adults. Here, we examine whether developmental hypoxia impacts subsequent hypoxia tolerance and aerobic performance of Atlantic salmon. Individuals at 8°C were exposed to 50% (hypoxia) or 100% (normoxia) dissolved oxygen (DO) saturation (as percent of air saturation) from fertilization for ∼100 d (800 degree days) and then raised in normoxic conditions for a further 15 mo. At 18 mo after fertilization, aerobic scope was calculated in normoxia (100% DO) and acute (18 h) hypoxia (50% DO) from the difference between the minimum and maximum oxygen consumption rates ([Formula: see text] and [Formula: see text], respectively) at 10°C. Hypoxia tolerance was determined as the DO at which loss of equilibrium (LOE) occurred in a constantly decreasing DO environment. There was no difference in [Formula: see text], [Formula: see text], or aerobic scope between fish raised in hypoxia or normoxia. There was some evidence that hypoxia tolerance was lower (higher DO at LOE) in hypoxia-raised fish compared with those raised in normoxia, but the magnitude of the effect was small (12.52% DO vs. 11.73% DO at LOE). Acute hypoxia significantly reduced aerobic scope by reducing [Formula: see text], while [Formula: see text] remained unchanged. Interestingly, acute hypoxia uncovered individual-level relationships between DO at LOE and [Formula: see text], [Formula: see text], and aerobic scope. We discuss our findings in the context of developmental trajectories and the role of aerobic performance in hypoxia tolerance.

Role of hypoxia and hypoxia inducible factor in physiological and pathological conditions

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Mozhgan Jahani

2017-11-01

Full Text Available Introduction: Organisms are exposed to oxygen deprivation (Hypoxia in various physiological and pathological conditions. There are different conserve evolutionary responses to counterview with this stress that primary transcriptional response to stress related to hypoxia is interceded by hypoxia-inducible factor (HIF-1 in mammals. This factor can regulate different genes that have essential roles in adaptation to this condition. In this review, the role of this factor in physiological and pathological conditions under hypoxic condition has been evaluated after examining structural features and regulation characteristics of HIF-1. Methods: First, articles related to the keywords of hypoxia and HIF-1 (from 1991-2016 were searched from valid databases such as Springer Link, Google Scholar, PubMed and Science direct. Then, the articles correlated with hypoxia, HIF-1 and their roles in physiological and pathological conditions (120 articles were searched and just 64 articles were selected for this study. Result: According to studies, there are different genes in cells and organs that can be regulated by HIF-1. Activation of genes expression by this protein occurs through its linkage to cis-acting of 50 base pair hypoxia response element (HRE region located in their promotor and enhancer. Depending on circumstances, activation of these genes can be beneficial or harmful. Conclusion: Activation of different genes in hypoxia by HIF-1 has different effects on physiological and pathological conditions. Therefore, HIF-1, as a hypoxia-inducible factor in hypoxic conditions, plays an essential role in the adaptation of cells and organs to changes related to the presence of oxygen.

Oxygen Concentration Inside a Functioning Photosynthetic Cell

OpenAIRE

Kihara, Shigeharu; Hartzler, Daniel A.; Savikhin, Sergei

2014-01-01

The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic...

Hypoxia is no hype: Perspectives across Phylogeny, Stem Cell differentiation & Geochemistry

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Editorial

2015-05-01

Full Text Available Influence of atmospheric gases in the eco systems on the habituating living organisms, an area of focus of the geochemists and astro-biologists, have been known for eons. Though the modus operandi of the implication varies between unicellular and multi-system centered organisms up in the ladder of phylogeny, their significance though known, the intricacies to the fullest extent have not been thoroughly understood to enable us to exploit them to our best in bringing solutions to address various problems. In this issue, Ito et al have reported a simple hypoxic culture system [1] with a built-in deoxidizing agent capable of promoting stem cell proliferation, repressing cell senescence without aggravating the stem cell viability. Studying hypoxia gains significance because oxygen exerts a profound influence on life on earth. Oxygen requirements differ across cells, tissues, organisms and phylogeny. The primitive life forms on earth which formed nearly four billion years ago were able to thrive without oxygen, which became a life influencing factor only two billion years ago during when its levels in the atmosphere were actually toxic to the organisms which evolved ways to detoxify them and over time these organisms became dependant on oxygen [2]. Among cellular processes, the low energy supply during a hypoxic metabolic state allows only DNA replication or basic cell reproduction functions which are essential for a cell’s survival suppressing the specialised functions like differentiation [2]. Thus, stemness is preserved more efficiently under hypoxia and it is suggested that in vitro stem cells should ideally be maintained at oxygen concentrations lower than 1% and approaching zero which recapitulate the atmospheric oxygen concentrations that existed on earth 2-3 billion years ago, as stem cells are believed to reflect an early evolutionary stage compared to other cells [2]. Hypoxia has shown to promote stemness in various kinds of stem cells

Hypoxia induced expression of endogenous markers in vitro is highly influenced by pH

International Nuclear Information System (INIS)

Sorensen, Brita Singers; Alsner, Jan; Overgaard, Jens; Horsman, Michael R.

2007-01-01

Background: Genes such as carbonic anhydrase IX (Ca9), glucose transporter 1 (Glut1), lactate dehydrogenase A (LDH-A), osteopontin (OPN) and lysyl oxidase (LOX) have been suggested as hypoxic markers, but inconsistent results suggest that factors other than oxygen influence their expression. The current study is a detailed investigation using a range of pH values from 6.3 to 7.5 in two human cell lines to establish the pH dependency of hypoxia induced gene expression. Methods: Human tumour cell lines (uterine cervix squamous cell carcinoma (SiHa) and pharyngeal squamous cell carcinoma [FaDu DD ]) were used. Hypoxia was induced by gassing cells in airtight chambers with various oxygen concentrations (21%, 1%, 0.1%, 0.01% and 0%) for up to 24 h. The media were titrated to a range of pH values (7.5, 7.0, 6.7, 6.5 and 6.3). Gene expression was determined by real-time PCR. Results: In both SiHa and FaDu DD cells Ca9 and LOX reached the highest level of expression at 1% oxygen. In FaDu DD cells, a pH of 6.5 had a medium suppression effect on the hypoxia induced expression of Ca9. pH 6.3 resulted in severe suppression of expression for Ca9 and LOX in both SiHa and FaDu DD . Glut1 and LDH-A had a similar expression pattern to each other, with a maximum expression at 0.01% oxygen, in both cell lines. For these genes pH 6.5 and 6.3 changed the expression pattern in SiHa cells. OPN was up regulated at low oxygen in SiHa cells, but was not induced by hypoxia in FaDu DD cells. Conclusion: As tumour hypoxia occurs in a deprived microenvironment, other environmental factors, for example low pH, might interact with the effect of low oxygen concentration on gene expression. This study shows that pH in two cell lines has a profound influence on the oxygen dependent induction of certain endogenous hypoxic markers

ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.

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Heimlich, J B; Speed, J S; Bloom, C J; O'Connor, P M; Pollock, J S; Pollock, D M

2015-03-01

This study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high-salt diet and/or hypoxia. C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to 3-h exposure to hypoxia (8% O₂) and/or 2 weeks of high-salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS). In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high-salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high-salt diet had approx. 150% higher glomerular ET-1 mRNA expression compared with a normal-salt diet (P ET-1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment. These data suggest that both hypoxia and a high-salt diet increase glomerular ROS production via endothelial-derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1-induced nephropathy. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

A Pilot Study of Inhaled CO Therapy in Neonatal Hypoxia-Ischemia: Carboxyhemoglobin Concentrations and Brain Volumes

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Martha Douglas-Escobar

2018-05-01

Full Text Available Objective: The objective of this pilot study was to start evaluating the efficacy and the safety (i.e., carboxyhemoglobin concentration of carbon monoxide (CO as a putative neuroprotective therapy in neonates.Study Design: Neonatal C57BL/6 mice were exposed to CO at a concentration of either 200 or 250 ppm for a period of 1 h. The pups were then sacrificed at 0, 10, 20, 60, 120, 180, and 240 min after exposure to either concentration of CO, and blood was collected for analysis of carboxyhemoglobin. Following the safety study, 7-day-old pups underwent a unilateral carotid ligation. After recovery, the pups were exposed to a humidified gas mixture of 8% oxygen and 92% nitrogen for 20 min in a hypoxia chamber. One hour after the hypoxia exposure, the pups were randomized to one of two groups: air (HI+A or carbon monoxide (HI+CO. An inhaled dose of 250 ppm of CO was administered to the pups for 1 h per day for a period of 3 days. At 7 days post-injury, the pups were sacrificed and the brains analyzed for cortical and hippocampal volumes.Results: CO exposure at 200 and 250 ppm produced a peak carboxyhemoglobin concentration of 21.52 ± 1.18% and 27.55 ± 3.58%, respectively. The carboxyhemoglobin concentrations decreased rapidly, reaching control concentrations by 60 min post exposure. At 14 days of age (7 days post injury, the HI+CO (treated with 1 h per day of 250 ppm of CO for 3 days post injury had significant preservation of the ratio of ipsilateral to contralateral cortex (median 1.07, 25% 0.97, 75% 1.23, n = 10 compared the HI+A group (p < 0.05.Conclusion: CO exposure of 250 ppm did not reach carboxyhemoglobin concentrations which would induce acute neurologic abnormalities and was effective in preserving cortical volumes following hypoxic-ischemic injury.

Hypoxia Enhances Differentiation of Adipose Tissue-Derived Stem Cells toward the Smooth Muscle Phenotype

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Fang Wang

2018-02-01

Full Text Available Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. The specific contractile properties of cells were verified with both a single cell contraction assay and a gel contraction assay. Five percent oxygen concentration significantly increased the expression levels of α-smooth muscle actin, calponin, and myosin heavy chain in adipose-derived stem cell cultures after 2 weeks of induction (p < 0.01. Cells differentiated in 5% oxygen conditions showed greater contraction effect (p < 0.01. Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells.

Hypoxia tolerance and air-breathing ability correlate with habitat preference in coral-dwelling fishes

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Nilsson, G. E.; Hobbs, J.-P. A.; Östlund-Nilsson, S.; Munday, P. L.

2007-06-01

Hypoxia tolerance and air-breathing occur in a range of freshwater, estuarine and intertidal fishes. Here it is shown for the first time that coral reef fishes from the genera Gobiodon, Paragobiodon and Caracanthus, which all have an obligate association with living coral, also exhibit hypoxia tolerance and a well-developed air-breathing capacity. All nine species maintained adequate respiration in water at oxygen concentrations down to 15-25% air saturation. This hypoxia tolerance is probably needed when the oxygen levels in the coral habitat drops sharply at night. Air-breathing abilities of the species correlated with habitat association, being greatest (equaling oxygen uptake in water) in species that occupy corals extending into shallow water, where they may become air exposed during extreme low tides. Air-breathing was less well-developed or absent in species inhabiting corals from deeper waters. Loss of scales and a network of subcutaneous capillaries appear to be key adaptations allowing cutaneous respiration in air. While hypoxia tolerance may be an ancestral trait in these fishes, air-breathing is likely to be a more recent adaptation exemplifying convergent evolution in the unrelated genera Gobiodon and Caracanthus in response to coral-dwelling lifestyles.

Regulation of mRNA translation influences hypoxia tolerance

International Nuclear Information System (INIS)

Koritzinsky, M.; Wouters, B.G.; Koumenis, C.

2003-01-01

Hypoxia is a heterogenous but common characteristic of human tumours and poor oxygenation is associated with poor prognosis. We believe that the presence of viable hypoxic tumor cells reflects in part an adaptation and tolerance of these cells to oxygen deficiency. Since oxidative phosphorylation is compromized during hypoxia, adaptation may involve both the upregulation of glycolysis as well as downregulation of energy consumption. mRNA translation is one of the most energy costly cellular processes, and we and others have shown that global mRNA translation is rapidly inhibited during hypoxia. However, some mRNAs, including those coding for HIF-1 α and VEGF, remain efficiently translated during hypoxia. Clearly, the mechanisms responsible for the overall inhibition of translation during hypoxia does not compromize the translation of certain hypoxia-induced mRNA species. We therefore hypothesize that the inhibition of mRNA translation serves to promote hypoxia tolerance in two ways: i) through conservation of energy and ii) through differential gene expression involved in hypoxia adaptation. We have recently identified two pathways that are responsible for the global inhibition of translation during hypoxia. The phosphorylation of the eukaryotic initiation factor eIF2 α by the ER resident kinase PERK results in down-regulation of protein synthesis shortly after the onset of hypoxia. In addition, the initiation complex eIF4F is disrupted during long lasting hypoxic conditions. The identification of the molecular pathways responsible for the inhibition of overall translation during hypoxia has rendered it possible to investigate their importance for hypoxia tolerance. We have found that mouse embryo fibroblasts that are knockout for PERK and therefore not able to inhibit protein synthesis efficiently during oxygen deficiency are significantly less tolerant to hypoxia than their wildtype counterparts. We are currently also investigating the functional significance

Hypothesis: the regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia.

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Devereux, Diana; Ikomi-Kumm, Julie

2013-03-01

The regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia is a hypothesis, which proposes an inherent operative system in homo sapiens that allows central nervous system and endocrine-mediated vascular system adaption to variables in partial pressure of oxygen, pH and body composition, while maintaining sufficient oxygen saturation for the immune system and ensuring protection of major organs in hypoxic and suboptimal conditions. While acknowledging the importance of the Henderson-Hasselbalch equation in the regulation of acid base balance, the hypothesis seeks to define the specific neuroendocrine/vascular mechanisms at work in regulating acid base balance in hypoxia and infection. The SIA (serotonin-immune-adrenergic) system is proposed as a working model, which allows central nervous system and endocrine-mediated macro- and micro vascular 'fine tuning'. The neurotransmitter serotonin serves as a 'hypoxic sensor' in concert with other operators to orchestrate homeostatic balance in normal and pathological states. The SIA system finely regulates oxygen, fuel and metabolic buffering systems at local sites to ensure optimum conditions for the immune response. The SIA system is fragile and its operation may be affected by infection, stress, diet, environmental toxins and lack of exercise. The hypothesis provides new insight in the area of neuro-gastroenterology, and emphasizes the importance of diet and nutrition as a complement in the treatment of infection, as well as the normalization of intestinal flora following antibiotic therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Oxygen concentration inside a functioning photosynthetic cell.

Science.gov (United States)

Kihara, Shigeharu; Hartzler, Daniel A; Savikhin, Sergei

2014-05-06

The excess oxygen concentration in the photosynthetic membranes of functioning oxygenic photosynthetic cells was estimated using classical diffusion theory combined with experimental data on oxygen production rates of cyanobacterial cells. The excess oxygen concentration within the plesiomorphic cyanobacterium Gloeobactor violaceus is only 0.025 μM, or four orders of magnitude lower than the oxygen concentration in air-saturated water. Such a low concentration suggests that the first oxygenic photosynthetic bacteria in solitary form could have evolved ∼2.8 billion years ago without special mechanisms to protect them against reactive oxygen species. These mechanisms instead could have been developed during the following ∼500 million years while the oxygen level in the Earth's atmosphere was slowly rising. Excess oxygen concentrations within individual cells of the apomorphic cyanobacteria Synechocystis and Synechococcus are 0.064 and 0.25 μM, respectively. These numbers suggest that intramembrane and intracellular proteins in isolated oxygenic photosynthetic cells are not subjected to excessively high oxygen levels. The situation is different for closely packed colonies of photosynthetic cells. Calculations show that the excess concentration within colonies that are ∼40 μm or larger in diameter can be comparable to the oxygen concentration in air-saturated water, suggesting that species forming colonies require protection against reactive oxygen species even in the absence of oxygen in the surrounding atmosphere. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The effects of exercise under hypoxia on cognitive function.

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Soichi Ando

Full Text Available Increasing evidence suggests that cognitive function improves during a single bout of moderate exercise. In contrast, exercise under hypoxia may compromise the availability of oxygen. Given that brain function and tissue integrity are dependent on a continuous and sufficient oxygen supply, exercise under hypoxia may impair cognitive function. However, it remains unclear how exercise under hypoxia affects cognitive function. The purpose of this study was to examine the effects of exercise under different levels of hypoxia on cognitive function. Twelve participants performed a cognitive task at rest and during exercise at various fractions of inspired oxygen (FIO2: 0.209, 0.18, and 0.15. Exercise intensity corresponded to 60% of peak oxygen uptake under normoxia. The participants performed a Go/No-Go task requiring executive control. Cognitive function was evaluated using the speed of response (reaction time and response accuracy. We monitored pulse oximetric saturation (SpO2 and cerebral oxygenation to assess oxygen availability. SpO2 and cerebral oxygenation progressively decreased during exercise as the FIO2 level decreased. Nevertheless, the reaction time in the Go-trial significantly decreased during moderate exercise. Hypoxia did not affect reaction time. Neither exercise nor difference in FIO2 level affected response accuracy. An additional experiment indicated that cognitive function was not altered without exercise. These results suggest that the improvement in cognitive function is attributable to exercise, and that hypoxia has no effects on cognitive function at least under the present experimental condition. Exercise-cognition interaction should be further investigated under various environmental and exercise conditions.

Hypoxia Induces a Metabolic Shift and Enhances the Stemness and Expansion of Cochlear Spiral Ganglion Stem/Progenitor Cells

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Hsin-Chien Chen

2015-01-01

Full Text Available Previously, we demonstrated that hypoxia (1% O2 enhances stemness markers and expands the cell numbers of cochlear stem/progenitor cells (SPCs. In this study, we further investigated the long-term effect of hypoxia on stemness and the bioenergetic status of cochlear spiral ganglion SPCs cultured at low oxygen tensions. Spiral ganglion SPCs were obtained from postnatal day 1 CBA/CaJ mouse pups. The measurement of oxygen consumption rate, extracellular acidification rate (ECAR, and intracellular adenosine triphosphate levels corresponding to 20% and 5% oxygen concentrations was determined using a Seahorse XF extracellular flux analyzer. After low oxygen tension cultivation for 21 days, the mean size of the hypoxia-expanded neurospheres was significantly increased at 5% O2; this correlated with high-level expression of hypoxia-inducible factor-1 alpha (Hif-1α, proliferating cell nuclear antigen (PCNA, cyclin D1, Abcg2, nestin, and Nanog proteins but downregulated expression of p27 compared to that in a normoxic condition. Low oxygen tension cultivation tended to increase the side population fraction, with a significant difference found at 5% O2 compared to that at 20% O2. In addition, hypoxia induced a metabolic energy shift of SPCs toward higher basal ECARs and higher maximum mitochondrial respiratory capacity but lower proton leak than under normoxia, where the SPC metabolism was switched toward glycolysis in long-term hypoxic cultivation.

Teleosts in hypoxia : Aspects of anaerobic metabolism

NARCIS (Netherlands)

Van den Thillart, G.; van Waarde, Aren

1985-01-01

Moderate hypoxia can be tolerated by many fish species, while only some species survive severe hypoxia or anoxia. Hypoxia usually activates anaerobic glycolysis, which may be temporary when the animals are able to improve their oxygen extraction capacity. Switching over to aerobic metabolism allows

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats.

Science.gov (United States)

Beharry, Kay D; Cai, Charles L; Skelton, Jacqueline; Siddiqui, Faisal; D'Agrosa, Christina; Calo, Johanna; Valencia, Gloria B; Aranda, Jacob V

2018-05-01

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O₂) with brief hypoxia (12% O₂); (2) RA with 12% O₂; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O₂ resolution. Interventions and initiatives to curtail O₂ variations should remain a high priority to prevent severe retinopathy.

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats

Directory of Open Access Journals (Sweden)

Kay D. Beharry

2018-05-01

Full Text Available Preterm infants often experience intermittent hypoxia (IH with resolution in room air (RA or hyperoxia (Hx between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1 Hx (50% O2 with brief hypoxia (12% O2; (2 RA with 12% O2; (3 Hx with RA; (4 Hx only; or (5 RA only, from P0 to P14. Pups were examined at P14 or placed in RA until P21. Retinal vascular and astrocyte integrity; retinal layer thickness; ocular and systemic biomarkers of angiogenesis; and somatic growth were determined at P14 and P21. All IH paradigms resulted in significant retinal vascular defects, disturbances in retinal astrocyte template, retinal thickening, and photoreceptor damage concurrent with elevations in angiogenesis biomarkers. These data suggest that the susceptibility of the immature retina to changes in oxygen render no differences in the outcomes between RA or O2 resolution. Interventions and initiatives to curtail O2 variations should remain a high priority to prevent severe retinopathy.

L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats

NARCIS (Netherlands)

Legrand, Matthieu; Almac, Emre; Mik, Egbert G.; Johannes, Tanja; Kandil, Asli; Bezemer, Rick; Payen, Didier; Ince, Can

2009-01-01

Legrand M, Almac E, Mik EG, Johannes T, Kandil A, Bezemer R, Payen D, Ince C. L-NIL prevents renal microvascular hypoxia and increase of renal oxygen consumption after ischemia-reperfusion in rats. Am J Physiol Renal Physiol 296: F1109-F1117, 2009. First published February 18, 2009;

Kinetic modeling in PET imaging of hypoxia

DEFF Research Database (Denmark)

Li, Fan; Jørgensen, Jesper Tranekjær; Hansen, Anders E

2014-01-01

be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET......Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can...... analysis for PET imaging of hypoxia....

Prolonged hypoxia increases survival even in Zebrafish (Danio rerio showing cardiac arrhythmia.

Directory of Open Access Journals (Sweden)

Renate Kopp

Full Text Available Tolerance towards hypoxia is highly pronounced in zebrafish. In this study even beneficial effects of hypoxia, specifically enhanced survival of zebrafish larvae, could be demonstrated. This effect was actually more pronounced in breakdance mutants, which phenotypically show cardiac arrhythmia. Breakdance mutants (bre are characterized by chronically reduced cardiac output. Despite an about 50% heart rate reduction, they become adults, but survival rate significantly drops to 40%. Normoxic bre animals demonstrate increased hypoxia inducible factor 1 a (Hif-1α expression, which indicates an activated hypoxic signaling pathway. Consequently, cardiovascular acclimation, like cardiac hypertrophy and increased erythrocyte concentration, occurs. Thus, it was hypothesized, that under hypoxic conditions survival might be even more reduced. When bre mutants were exposed to hypoxic conditions, they surprisingly showed higher survival rates than under normoxic conditions and even reached wildtype values. In hypoxic wildtype zebrafish, survival yet exceeded normoxic control values. To specify physiological acclimation, cardiovascular and metabolic parameters were measured before hypoxia started (3 dpf, when the first differences in survival rate occurred (7 dpf and when survival rate plateaued (15 dpf. Hypoxic animals expectedly demonstrated Hif-1α accumulation and consequently enhanced convective oxygen carrying capacity. Moreover, bre animals showed a significantly enhanced heart rate under hypoxic conditions, which reached normoxic wildtype values. This improvement in convective oxygen transport ensured a sufficient oxygen and nutrient supply and was also reflected in the significantly higher mitochondrial activity. The highly optimized energy metabolism observed in hypoxic zebrafish larvae might be decisive for periods of higher energy demand due to organ development, growth and increased activity. However, hypoxia increased survival only during a

Oxygen hypothesis of polar gigantism not supported by performance of Antarctic pycnogonids in hypoxia

Science.gov (United States)

Woods, H. Arthur; Moran, Amy L.; Arango, Claudia P.; Mullen, Lindy; Shields, Chris

2008-01-01

Compared to temperate and tropical relatives, some high-latitude marine species are large-bodied, a phenomenon known as polar gigantism. A leading hypothesis on the physiological basis of gigantism posits that, in polar water, high oxygen availability coupled to low metabolic rates relieves constraints on oxygen transport and allows the evolution of large body size. Here, we test the oxygen hypothesis using Antarctic pycnogonids, which have been evolving in very cold conditions (−1.8–0°C) for several million years and contain spectacular examples of gigantism. Pycnogonids from 12 species, spanning three orders of magnitude in body mass, were collected from McMurdo Sound, Antarctica. Individual sea spiders were forced into activity and their performance was measured at different experimental levels of dissolved oxygen (DO). The oxygen hypothesis predicts that, all else being equal, large pycnogonids should perform disproportionately poorly in hypoxia, an outcome that would appear as a statistically significant interaction between body size and oxygen level. In fact, although we found large effects of DO on performance, and substantial interspecific variability in oxygen sensitivity, there was no evidence for size×DO interactions. These data do not support the oxygen hypothesis of Antarctic pycnogonid gigantism and suggest that explanations must be sought in other ecological or evolutionary processes. PMID:19129117

Mechanisms Causing Hypoxia in the Baltic Sea at Different Spatial and Temporal Scales

Science.gov (United States)

Conley, D. J.; Carstensen, J.; Gustafsson, B.; Slomp, C. P.

2016-02-01

A number of synthesis efforts have documented the world-wide increase in hypoxia, which is primarily driven by nutrient inputs with consequent organic matter enrichment. Physical factors including freshwater or saltwater inputs, stratification and temperature also play an important role in causing and sustaining hypoxia. The Baltic Sea provides an interesting case study to examine changes in oxygen dynamics over time because of the diversity of the types of hypoxia that occur, which ranges from episodic to seasonal hypoxia to perennial hypoxia. Hypoxia varies spatially across the basin with differences between open water bottoms and coastal systems. In addition, the extent and intensity of hypoxia has also varied greatly over the history of the basin, e.g. the last 8000 years. We will examine the mechanisms causing hypoxia at different spatial and temporal scales. The hydrodynamical setting is an important governing factor controlling possible time scales of hypoxia, but enhanced nutrient fluxes and global warming amplify oxygen depletion when oxygen supply by physical processes cannot meet oxygen demands from respiration. Our results indicate that climate change is counteracting management efforts to reduce hypoxia. We will address how hypoxia in the Baltic Sea is terminated at different scales. More importantly, we will explore the prospects of getting rid of hypoxia with the nutrient reductions that have been agreed upon by the countries in the Baltic Sea basin and discuss the time scales of improvement in bottom water oxygen conditions.

Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor

International Nuclear Information System (INIS)

Jeong, Wooyoung; Bazer, Fuller W.; Song, Gwonhwa; Kim, Jinyoung

2016-01-01

The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurred when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de

Expression of hypoxia-inducible factor-1 by trophectoderm cells in response to hypoxia and epidermal growth factor

Energy Technology Data Exchange (ETDEWEB)

Jeong, Wooyoung [Department of Animal Resources Science, Dankook University, Cheonan (Korea, Republic of); Bazer, Fuller W. [Center for Animal Biotechnology and Genomics and Department of Animal Science, Texas A& M University, College Station, TX (United States); Song, Gwonhwa, E-mail: ghsong@korea.ac.kr [Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Kim, Jinyoung, E-mail: jinyoungkim@dankook.ac.kr [Department of Animal Resources Science, Dankook University, Cheonan (Korea, Republic of)

2016-01-08

The low oxygen environment in the uterine environment requires pre-implantation embryos to adapt to oxygen deficiency. Hypoxia-inducible factor (HIF)-1 is a master regulator whereby cells adapt to changes in oxygen concentrations. In addition to hypoxic conditions, non-hypoxic stimuli such as growth factors also activate expression of HIF-1. In this study, the mechanisms underlying low oxygen-dependent and epidermal growth factor (EGF)-dependent expression of HIF-1α were explored using porcine trophectoderm (pTr) cells. The results indicated that expression of HIF-1α and HIF-1β mRNAs was not affected by low concentrations of oxygen; however, hypoxic conditions markedly increased the abundance of HIF-1α protein, especially in nuclei of pTr cells. Even under normoxic conditions, the abundance of HIF-1α protein increased in response to EGF. This EGF-mediated increase in HIF-1α protein was blocked through inhibition of translation by cycloheximide. The inhibitors LY294002 (PI3K-AKT inhibitor), U0126 (inhibitor of ERK1/2) and rapamycin (mTOR inhibitor) also blocked the ability of EGF to increase HIF-1α protein and to phosphorylate AKT, ERK1/2 and mTOR proteins. Both hypoxia and EGF induced proliferation of pTr cells. This ability of EGF to stimulate proliferation of pTr cells was suppressed by EGFR siRNA, but not HIF-1α siRNA, but a significant decrease in EGF-induced HIF-1α protein occurred when pTr cells were transfected with HIF-1α siRNA. The results of the present study suggest that pTr cells adapt to oxygen deficiency and proliferate in response to an oxygen-dependent HIF-1 system, and that EGF at maternal–conceptus interface can increase the abundance of HIF-1α protein via translational regulation through AKT, ERK1/2 and mTOR signaling cascades. - Highlights: • HIF-1α expression is up-regulated in pTr cells under low oxygen concentrations. • EGF induces HIF-1α accumulation in pTr cells. • EGF-induced HIF-1α accumulation is blocked by de

A Lab Assembled Microcontroller-Based Sensor Module for Continuous Oxygen Measurement in Portable Hypoxia Chambers

OpenAIRE

Mathupala, Saroj P.; Kiousis, Sam; Szerlip, Nicholas J.

2016-01-01

Background Hypoxia-based cell culture experiments are routine and essential components of in vitro cancer research. Most laboratories use low-cost portable modular chambers to achieve hypoxic conditions for cell cultures, where the sealed chambers are purged with a gas mixture of preset O2 concentration. Studies are conducted under the assumption that hypoxia remains unaltered throughout the 48 to 72 hour duration of such experiments. Since these chambers lack any sensor or detection system t...

Physiological oxygen concentration alters glioma cell malignancy and responsiveness to photodynamic therapy in vitro.

Science.gov (United States)

Albert, Ina; Hefti, Martin; Luginbuehl, Vera

2014-11-01

The partial pressure of oxygen (pO2) in brain tumors ranges from 5 to 15%. Nevertheless, the majority of in vitro experiments with glioblastoma multiforme (GBM) cell lines are carried out under an atmospheric pO2 of 19 to 21%. Recently, 5-aminolevulinic acid (5-ALA), a precursor of protoporphyrin IX (PpIX), has been introduced to neurosurgery to allow for photodynamic diagnosis and photodynamic therapy (PDT) in high-grade gliomas. Here, we investigate whether low pO2 affects GBM cell physiology, PpIX accumulation, or PDT efficacy. GBM cell lines (U-87 MG and U-251 MG) were cultured under atmospheric (pO2  =  19%) and physiological (pO2  =  9%) oxygen concentrations. PpIX accumulation and localization were investigated, and cell survival and cell death were observed following in vitro PDT. A physiological pO2 of 9% stimulated GBM cell migration, increased hypoxia-inducible factor (HIF)-1 alpha levels, and elevated resistance to camptothecin in U-87 MG cells compared to cultivation at a pO2 of 19%. This oxygen reduction did not alter 5-ALA-induced intracellular PpIX accumulation. However, physiological pO2 changed the responsiveness of U-87 MG but not of U-251 MG cells to in vitro PDT. Around 20% more irradiation light was required to kill U-87 MG cells at physiological pO2, resulting in reduced lactate dehydrogenase (LDH) release (one- to two-fold) and inhibition of caspase 3 activation. Reduction of oxygen concentration from atmospheric to a more physiological level can influence the malignant behavior and survival of GBM cell lines after in vitro PDT. Therefore, precise oxygen concentration control should be considered when designing and performing experiments with GBM cells.

Improvement of oxygen supply by an artificial carrier in combination with normobaric oxygenation decreases the volume of tissue hypoxia and tissue damage from transient focal cerebral ischemia

NARCIS (Netherlands)

Seiffge, David J.; Lapina, Natalia E.; Tsagogiorgas, Charalambos; Theisinger, Bastian; Henning, Robert H.; Schilling, Lothar

Tissue hypoxia may play an important role in the development of ischemic brain damage. In the present study we investigated in a rat model of transient focal brain ischemia the neuroprotective effects of increasing the blood oxygen transport capacity by applying a semifluorinated alkane

Tissue hypoxia during ischemic stroke: adaptive clues from hypoxia-tolerant animal models.

Science.gov (United States)

Nathaniel, Thomas I; Williams-Hernandez, Ashley; Hunter, Anan L; Liddy, Caroline; Peffley, Dennis M; Umesiri, Francis E; Imeh-Nathaniel, Adebobola

2015-05-01

The treatment and prevention of hypoxic/ischemic brain injury in stroke patients remain a severe and global medical issue. Numerous clinical studies have resulted in a failure to develop chemical neuroprotection for acute, ischemic stroke. Over 150 estimated clinical trials of ischemic stroke treatments have been done, and more than 200 drugs and combinations of drugs for ischemic and hemorrhagic strokes have been developed. Billions of dollars have been invested for new scientific breakthroughs with only limited success. The revascularization of occluded cerebral arteries such as anti-clot treatments of thrombolysis has proven effective, but it can only be used in a 3-4.5h time frame after the onset of a stroke, and not for every patient. This review is about novel insights on how to resist tissue hypoxia from unconventional animal models. Ability to resist tissue hypoxia is an extraordinary ability that is not common in many laboratory animals such as rat and mouse models. For example, we can learn from a naked mole-rat, Chrysemys picta, how to actively regulate brain metabolic activity to defend the brain against fluctuating oxygen tension and acute bouts of oxidative stress following the onset of a stroke. Additionally, a euthermic arctic ground squirrel can teach us how the brain of a stroke patient can remain well oxygenated during tissue hypoxia with no evidence of cellular stress. In this review, we discuss how these animals provide us with a system to gain insight into the possible mechanisms of tissue hypoxia/ischemia. This issue is of clinical significance to stroke patients. We describe specific physiological and molecular adaptations employed by different animals' models of hypoxia tolerance in aquatic and terrestrial environments. We highlight how these adaptations might provide potential clues on strategies to adapt for the clinical management of tissue hypoxia during conditions such as stroke where oxygen demand fails to match the supply. Copyright

Optical imaging of tumor hypoxia dynamics

Science.gov (United States)

Palmer, Gregory M.; Fontanella, Andrew N.; Zhang, Guoqing; Hanna, Gabi; Fraser, Cassandra L.; Dewhirst, Mark W.

2010-11-01

The influence of the tumor microenvironment and hypoxia plays a significant role in determining cancer progression, treatment response, and treatment resistance. That the tumor microenvironment is highly heterogeneous with significant intratumor and intertumor variability presents a significant challenge in developing effective cancer therapies. Critical to understanding the role of the tumor microenvironment is the ability to dynamically quantify oxygen levels in the vasculature and tissue in order to elucidate the roles of oxygen supply and consumption, spatially and temporally. To this end, we describe the use of hyperspectral imaging to characterize hemoglobin absorption to quantify hemoglobin content and oxygen saturation, as well as dual emissive fluorescent/phosphorescent boron nanoparticles, which serve as ratiometric indicators of tissue oxygen tension. Applying these techniques to a window-chamber tumor model illustrates the role of fluctuations in hemoglobin saturation in driving changes in tissue oxygenation, the two being significantly correlated (r = 0.77). Finally, a green-fluorescence-protein reporter for hypoxia inducible factor-1 (HIF-1) provides an endpoint for hypoxic stress in the tumor, which is used to demonstrate a significant association between tumor hypoxia dynamics and HIF-1 activity in an in vivo demonstration of the technique.

Hypoxia, but not an electrolyte-imbalanced diet, reduces feed intake, growth and oxygen consumption in rainbow trout (Oncorhynchus mykiss)

NARCIS (Netherlands)

Magnoni, Leonardo J.; Eding, Ep; Leguen, Isabelle; Prunet, Patrick; Geurden, Inge; Ozório, Rodrigo O.A.; Schrama, Johan W.

2018-01-01

Oxygen limitation and dietary imbalances are key aspects influencing feed intake (FI) and growth performance in cultured fish. This study investigated the combined effects of hypoxia and dietary electrolyte balance on the growth performance, body composition and nutrient utilization in a rainbow

Methods of Blood Oxygen Level-Dependent Magnetic Resonance Imaging Analysis for Evaluating Renal Oxygenation

Directory of Open Access Journals (Sweden)

Fen Chen

2018-03-01

Full Text Available Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI has recently been utilized as a noninvasive tool for evaluating renal oxygenation. Several methods have been proposed for analyzing BOLD images. Regional ROI selection is the earliest and most widely used method for BOLD analysis. In the last 20 years, many investigators have used this method to evaluate cortical and medullary oxygenation in patients with ischemic nephropathy, hypertensive nephropathy, diabetic nephropathy, chronic kidney disease (CKD, acute kidney injury and renal allograft rejection. However, clinical trials of BOLD MRI using regional ROI selection revealed that it was difficult to distinguish the renal cortico-medullary zones with this method, and that it was susceptible to observer variability. To overcome these deficiencies, several new methods were proposed for analyzing BOLD images, including the compartmental approach, fractional hypoxia method, concentric objects (CO method and twelve-layer concentric objects (TLCO method. The compartmental approach provides an algorithm to judge whether the pixel belongs to the cortex or medulla. Fractional kidney hypoxia, measured by using BOLD MRI, was negatively correlated with renal blood flow, tissue perfusion and glomerular filtration rate (GFR in patients with atherosclerotic renal artery stenosis. The CO method divides the renal parenchyma into six or twelve layers of thickness in each coronal slice of BOLD images and provides a R2* radial profile curve. The slope of the R2* curve associated positively with eGFR in CKD patients. Indeed, each method invariably has advantages and disadvantages, and there is generally no consensus method so far. Undoubtedly, analytic approaches for BOLD MRI with better reproducibility would assist clinicians in monitoring the degree of kidney hypoxia and thus facilitating timely reversal of tissue hypoxia.

Impact of Pancreatic Rat Islet Density on Cell Survival during Hypoxia

Directory of Open Access Journals (Sweden)

A. Rodriguez-Brotons

2016-01-01

Full Text Available In bioartificial pancreases (BP, the number of islets needed to restore normoglycaemia in the diabetic patient is critical. However, the confinement of a high quantity of islets in a limited space may impact islet survival, particularly in regard to the low oxygen partial pressure (PO2 in such environments. The aim of the present study was to evaluate the impact of islet number in a confined space under hypoxia on cell survival. Rat islets were seeded at three different concentrations (150, 300, and 600 Islet Equivalents (IEQ/cm2 and cultured in normal atmospheric pressure (160 mmHg as well as hypoxic conditions (15 mmHg for 24 hours. Cell viability, function, hypoxia-induced changes in gene expression, and cytokine secretion were then assessed. Notably, hypoxia appeared to induce a decrease in viability and increasing islet density exacerbated the observed increase in cellular apoptosis as well as the loss of function. These changes were also associated with an increase in inflammatory gene transcription. Taken together, these data indicate that when a high number of islets are confined to a small space under hypoxia, cell viability and function are significantly impacted. Thus, in order to improve islet survival in this environment during transplantation, oxygenation is of critical importance.

HRE-type genes are regulated by growth-related changes in internal oxygen concentrations during the normal development of potato (Solanum tuberosum) tubers.

Science.gov (United States)

Licausi, Francesco; Giorgi, Federico Manuel; Schmälzlin, Elmar; Usadel, Björn; Perata, Pierdomenico; van Dongen, Joost Thomas; Geigenberger, Peter

2011-11-01

The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.

Hypoxia in the changing marine environment

Science.gov (United States)

Zhang, J.; Cowie, G.; Naqvi, S. W. A.

2013-03-01

The predicted future of the global marine environment, as a combined result of forcing due to climate change (e.g. warming and acidification) and other anthropogenic perturbation (e.g. eutrophication), presents a challenge to the sustainability of ecosystems from tropics to high latitudes. Among the various associated phenomena of ecosystem deterioration, hypoxia can cause serious problems in coastal areas as well as oxygen minimum zones in the open ocean (Diaz and Rosenberg 2008 Science 321 926-9, Stramma et al 2008 Science 320 655-8). The negative impacts of hypoxia include changes in populations of marine organisms, such as large-scale mortality and behavioral responses, as well as variations of species distributions, biodiversity, physiological stress, and other sub-lethal effects (e.g. growth and reproduction). Social and economic activities that are related to services provided by the marine ecosystems, such as tourism and fisheries, can be negatively affected by the aesthetic outcomes as well as perceived or real impacts on seafood quality (STAP 2011 (Washington, DC: Global Environment Facility) p 88). Moreover, low oxygen concentration in marine waters can have considerable feedbacks to other compartments of the Earth system, like the emission of greenhouse gases to the atmosphere, and can affect the global biogeochemical cycles of nutrients and trace elements. It is of critical importance to prediction and adaptation strategies that the key processes of hypoxia in marine environments be precisely determined and understood (cf Zhang et al 2010 Biogeosciences 7 1-24).

[The effect of altered oxygen partial pressure on the resisitance to hypoxia and expression of oxygen-sensitive genes in Drosophila melanogaster].

Science.gov (United States)

Berezovs'kyĭ, V Ia; Chaka, O H; Litovka, I H; Levashov, M I; Ianko, R V

2014-01-01

As a result of resistance test to hypoxia of Drosophilas melanogaster of Oregon strain, we identified a high resistance (Group II) and low resistance (Group III) subpopulations of flies. Flies from groups II and III were incubated in a constant normobaric hypoxia (Po2=62-64 mm Hg) for 10 generations. A highly resistant group (Group IV) were exposed to a shortterm anoxia (Po,=1,5 mm Hg, 5 min) every generation. Larvae from Groups II, III, and IV demonstrated significantly elevated levels of Sir and CG 14740 expression. Larvae from Group II had a significantly higher expression of CG 14740 compared to group III. The restitution time after exposure to anoxia was significantly reduced in Group II (on 31% of the control values) Our results suggest that long-term adaptation to low oxygen partial pressure of highly resistant Drosophila significantly reduces the time of restitution and increases the expression of Sir2 and CG14740 genes.

Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

International Nuclear Information System (INIS)

Wilson, W.R.; Patterson, A.V.

2003-01-01

There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

Variability and Dynamics of Dissolved Oxygen in the Transition Zone of the North Sea and the Baltic Sea

DEFF Research Database (Denmark)

Jonasson, Lars

information about the seasonal to decadal oxygen variations in the bottom water of the Kattegat, the Danish Straits, the Sound and the Western Baltic Sea and investigates the relative importance of physical and biogeochemical processes, climate change and nutrient load reductions on the oxygen variability......The bottom water in the transition zone of the North Sea and Baltic Sea suffers from seasonal hypoxia, usually during late summer and autumn. Hypoxia is a natural phenomenon in this region because of the strong vertical stratification which prevents the bottom water to be ventilated by atmospheric...... concentrations by 15-30 μmol O2 l−1 yr−1 while the reduced nutrient concentration has increased the oxygen concentration with approximately the same amount. Thus, the positive effect on oxygen conditions from reduced nutrient concentrations have been counteracted by increased water temperatures. This has made...

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

Science.gov (United States)

Sørensen, Brita Singers; Busk, Morten; Overgaard, Jens; Horsman, Michael R; Alsner, Jan

2015-01-01

The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect), which weakens the spatial linkage between hypoxia and acidosis. Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15) were treated with hypoxia, acidosis (pH 6.3), or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein. Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe), genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2), and Ribosomal protein L37 (RPL37). Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa) and protein synthesis (both cell lines) was observed when hypoxia and low pHe were combined. We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de novo

Gene expression promoted by the SV40 DNA targeting sequence and the hypoxia-responsive element under normoxia and hypoxia

Directory of Open Access Journals (Sweden)

C.B. Sacramento

2010-08-01

Full Text Available The main objective of the present study was to find suitable DNA-targeting sequences (DTS for the construction of plasmid vectors to be used to treat ischemic diseases. The well-known Simian virus 40 nuclear DTS (SV40-DTS and hypoxia-responsive element (HRE sequences were used to construct plasmid vectors to express the human vascular endothelial growth factor gene (hVEGF. The rate of plasmid nuclear transport and consequent gene expression under normoxia (20% O2 and hypoxia (less than 5% O2 were determined. Plasmids containing the SV40-DTS or HRE sequences were constructed and used to transfect the A293T cell line (a human embryonic kidney cell line in vitro and mouse skeletal muscle cells in vivo. Plasmid transport to the nucleus was monitored by real-time PCR, and the expression level of the hVEGF gene was measured by ELISA. The in vitro nuclear transport efficiency of the SV40-DTS plasmid was about 50% lower under hypoxia, while the HRE plasmid was about 50% higher under hypoxia. Quantitation of reporter gene expression in vitro and in vivo, under hypoxia and normoxia, confirmed that the SV40-DTS plasmid functioned better under normoxia, while the HRE plasmid was superior under hypoxia. These results indicate that the efficiency of gene expression by plasmids containing DNA binding sequences is affected by the concentration of oxygen in the medium.

The effects of hypoxia on active ionic transport processes in the gill epithelium of hyperregulating crab, Carcinus maneas.

Science.gov (United States)

Lucu, Čedomil; Ziegler, Andreas

2017-09-01

Effects of hypoxia on the osmorespiratory functions of the posterior gills of the shore crab Carcinus maenas acclimated to 12ppt seawater (DSW) were studied. Short-circuit current (Isc) across the hemilamella (one epithelium layer supported by cuticle) was substantially reduced under exposure to 1.6, 2.0, or 2.5mg O 2 /L hypoxic saline (both sides of epithelium) and fully recovered after reoxygenation. Isc was reduced equally in the epithelium exposed to 1.6mg O 2 /L on both sides and when the apical side was oxygenated and the basolateral side solely exposed to hypoxia. Under 1.6mg O 2 /L, at the level of maximum inhibition of Isc, conductance was decreased from 40.0mScm -2 to 34.7mScm -2 and fully recovered after reoxygenation. Isc inhibition under hypoxia and reduced 86 Rb + (K + ) fluxes across apically located K + channels were caused preferentially by reversible inhibition of basolaterally located and ouabain sensitive Na + ,K + -ATPase mediated electrogenic transport. Reversible inhibition of Isc is discussed as decline in active transport energy supply down regulating metabolic processes and saving energy during oxygen deprivation. In response to a 4day exposure of Carcinus to 2.0mg O 2 /L, hemolymph Na + and Cl - concentration decreased, i.e. hyperosmoregulation was weakened. Variations of the oxygen concentration level and exposure time to hypoxia lead to an increase of the surface of mitochondria per epithelium area and might in part compensate for the decrease in oxygen availability under hypoxic conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Hypoxia-inducible factor signalling mechanisms in the central nervous system.

Science.gov (United States)

Corcoran, A; O'Connor, J J

2013-08-01

In the CNS, neurones are highly sensitive to the availability of oxygen. In conditions where oxygen availability is decreased, neuronal function can be altered, leading to injury and cell death. Hypoxia has been implicated in a number of central nervous system pathologies including stroke, head trauma and neurodegenerative diseases. Cellular responses to oxygen deprivation are complex and result in activation of short- and long-term mechanisms to conserve energy and protect cells. Failure of synaptic transmission can be observed within minutes following this hypoxia. The acute effects of hypoxia on synaptic transmission are primarily mediated by altering ion fluxes across membranes, pre-synaptic effects of adenosine and other actions at glutamatergic receptors. A more long-term feature of the response of neurones to hypoxia is the activation of transcription factors such as hypoxia-inducible factor. The activation of hypoxia-inducible factor is governed by a family of dioxygenases called hypoxia-inducible factor prolyl 4 hydroxylases (PHDs). Under hypoxic conditions, PHD activity is inhibited, thereby allowing hypoxia-inducible factor to accumulate and translocate to the nucleus, where it binds to the hypoxia-responsive element sequences of target gene promoters. Inhibition of PHD activity stabilizes hypoxia-inducible factor and other proteins thus acting as a neuroprotective agent. This review will focus on the response of neuronal cells to hypoxia-inducible factor and its targets, including the prolyl hydroxylases. We also present evidence for acute effects of PHD inhibition on synaptic transmission and plasticity in the hippocampus. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The expanding universe of hypoxia.

Science.gov (United States)

Zhang, Huafeng; Semenza, Gregg L

2008-07-01

Reduced oxygen availability (hypoxia) is sensed and transduced into changes in the activity or expression of cellular macromolecules. These responses impact on virtually all areas of biology and medicine. In this meeting report, we summarize major developments in the field that were presented at the 2008 Keystone Symposium on Cellular, Physiological, and Pathogenic Responses to Hypoxia.

Nitroimidazoles and imaging hypoxia

International Nuclear Information System (INIS)

Nunn, A.; Linder, K.; Strauss, H.W.

1995-01-01

A class of compounds known to undergo different intracellular metabolism depending on the availability of oxygen in tissue, the nitroimidazoles, have been advocated for imaging hypoxic tissue. In the presence of normal oxygen levels the molecule is immediately reoxidized. In hypoxic tissue the low oxygen concentration is not able to effectively compete to reoxidize the molecule and further reduction appears to take place. The association is not irreversible. Nitroimidazoles for in vivo imaging using radiohalogenated derivatives of misonidazole have recently been employed in patients. Two major problems with fluoromisonidazole are its relatively low concentration within the lesion and the need to wait several hours to permit clearance of the agent from the normoxic background tissue. Even with high-resolution positron emission tomographic imaging, this combination of circumstances makes successful evaluation of hypoxic lesions a challenge. Single-photon agents, with their longer half-lives and comparable biological properties, offer a greater opportunity for successful imaging. In 1992 technetium-99m labeled nitroimidazoles were described that seem to have at least comparable in vivo characteristics. Laboratory studies have demonstrated preferential binding of these agents to hypoxic tissue in the myocardium, in the brain, and in tumors. These investigations indicate that imaging can provide direct evidence of tissue with low oxygen levels that is viable. Even from this early vantage point the utility of measuring tissue oxygen levels with external imaging suggests that hypoxia imaging could play a major role in clinical decision making. (orig./MG)

The effect of acute hypoxia on short-circuit current and epithelial resistivity in biopsies from human colon.

Science.gov (United States)

Carra, Graciela E; Ibáñez, Jorge E; Saraví, Fernando D

2013-09-01

In isolated colonic mucosa, decreases in short-circuit current (ISC) and transepithelial resistivity (RTE) occur when hypoxia is either induced at both sides or only at the serosal side of the epithelium. We assessed in human colon biopsies the sensitivity to serosal-only hypoxia and mucosal-only hypoxia and whether Na, K-ATPase blockade with ouabain interacts with hypoxia. Biopsy material from patients undergoing colonoscopy was mounted in an Ussing chamber for small samples (1-mm2 window). In a series of experiments we assessed viability and the electrical response to the mucolytic, dithiothreitol (1 mmol/l). In a second series, we explored the effect of hypoxia without and with ouabain. In a third series, we evaluated the response to a cycle of hypoxia and reoxygenation induced at the serosal or mucosal side while keeping the oxygenation of the opposite side. 1st series: Dithiothreitol significantly decreased the unstirred layer and ISC but increased RTE. 2nd series: Both hypoxia and ouabain decreased ISC, but ouabain increased RTE and this effect on RTE prevailed even during hypoxia. 3rd series: Mucosal hypoxia caused lesser decreases of ISC and RTE than serosal hypoxia; in the former, but not in the latter, recovery was complete upon reoxygenation. In mucolytic concentration, dithiothreitol modifies ISC and RTE. Oxygen supply from the serosal side is more important to sustain ISC and RTE in biopsy samples. The different effect of hypoxia and Na, K-ATPase blockade on RTE suggests that their depressing effect on ISC involves different mechanisms.

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.

Science.gov (United States)

Lee, Chang-Joon; Gardiner, Bruce S; Ngo, Jennifer P; Kar, Saptarshi; Evans, Roger G; Smith, David W

2017-08-01

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo 2 ) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo 2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo 2 The model parameters analyzed were as follows: 1 ) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po 2 , hemoglobin concentration, and renal blood flow); 2 ) the major determinants of renal oxygen consumption (V̇o 2 ) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (β)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo 2 to the major the determinants of [Formula: see text] and V̇o 2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease. Copyright © 2017 the American Physiological Society.

Understanding and exploiting the genomic response to hypoxia

International Nuclear Information System (INIS)

Giaccia, A.J.

2003-01-01

The tumor microenvironment influences both therapeutic outcome and malignant progression. Of the many factors that may be altered in the tumor microenvironment, changes in tumor oxygenation have been strongly associated with a lower probability of local tumor control and survival. In vitro studies indicate that cells exposed to a low oxygen environment exhibit multiple phenotypes, including cell-cycle arrest, increased expression of pro-angiogenic genes, increased invasive capacity, increased apoptosis, increased anaerobic metabolism and altered differentiation programs. While the mechanistic basis of hypoxia as an impediment to radiotherapy and chemotherapy is well understood, it is unclear what changes in the cellular phenotype are important in understanding how hypoxia modifies malignant progression. One insight into how hypoxia modulates malignant progression comes from understanding the critical transcriptional regulators of gene expression under hypoxic conditions such as hypoxia inducible factor 1 (HIF-1) as well as changes in gene expression in untransformed and transformed cells. Overall, about 1.5% of the genome is found to be transcriptionally responsive to changes in oxygenation. Most importantly, the coordinated changes in gene expression under hypoxic conditions underscore the physiologic basis for altering gene expression in response to a low oxygen environment. In addition, some hypoxia-induced genes exhibit increased expression after reoxygenation, suggesting that they are regulated both by hypoxia and oxidative stress. Analysis of the genomic response to hypoxia has several therapeutic uses. First, it allows one to ask the question of what the cellular consequences are to inhibition of the transcriptional response to hypoxia such as by targeting the HIF-1 transcription factor. While the effect of loss of HIF-1 in tumors leads to inhibition of tumor growth, it does not eliminate tumors. In fact, studies indicate that inhibition of HIF-1 leads to a

Three hours of intermittent hypoxia increases circulating glucose levels in healthy adults.

Science.gov (United States)

Newhouse, Lauren P; Joyner, Michael J; Curry, Timothy B; Laurenti, Marcello C; Man, Chiara Dalla; Cobelli, Claudio; Vella, Adrian; Limberg, Jacqueline K

2017-01-01

An independent association exists between sleep apnea and diabetes. Animal models suggest exposure to intermittent hypoxia, a consequence of sleep apnea, results in altered glucose metabolism and fasting hyperglycemia. However, it is unknown if acute exposure to intermittent hypoxia increases glucose concentrations in nondiabetic humans. We hypothesized plasma glucose would be increased from baseline following 3 h of intermittent hypoxia in healthy humans independent of any effect on insulin sensitivity. Eight (7M/1F, 21-34 years) healthy subjects completed two study visits randomized to 3 h of intermittent hypoxia or continuous normoxia, followed by an oral glucose tolerance test. Intermittent hypoxia consisted of 25 hypoxic events per hour where oxygen saturation (SpO 2 ) was significantly reduced (Normoxia: 97 ± 1%, Hypoxia: 90 ± 2%, P  0.05). In contrast, circulating glucose concentrations were increased after 3 h of intermittent hypoxia when compared to baseline (5.0 ± 0.2 vs. 5.3 ± 0.2 mmol/L, P = 0.01). There were no detectable changes in insulin sensitivity following intermittent hypoxia when compared to continuous normoxia, as assessed by the oral glucose tolerance test (P > 0.05). Circulating glucose is increased after 3 h of intermittent hypoxia in healthy humans, independent of any lasting changes in insulin sensitivity. These novel findings could explain, in part, the high prevalence of diabetes in patients with sleep apnea and warrant future studies to identify underlying mechanisms. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Hypoxia Tolerance and Metabolic Suppression in Oxygen Minimum Zone Euphausiids: Implications for Ocean Deoxygenation and Biogeochemical Cycles

KAUST Repository

Seibel, Brad A.

2016-08-10

The effects of regional variations in oxygen and temperature levels with depth were assessed for the metabolism and hypoxia tolerance of dominant euphausiid species. The physiological strategies employed by these species facilitate prediction of changing vertical distributions with expanding oxygen minimum zones and inform estimates of the contribution of vertically migrating species to biogeochemical cycles. The migrating species from the Eastern Tropical Pacific (ETP), Euphausia eximia and Nematoscelis gracilis, tolerate a Partial Pressure (PO2) of 0.8 kPa at 10 °C (∼15 µM O2) for at least 12 h without mortality, while the California Current species, Nematoscelis difficilis, is incapable of surviving even 2.4 kPa PO2 (∼32 µM O2) for more than 3 h at that temperature. Euphausia diomedeae from the Red Sea migrates into an intermediate oxygen minimum zone, but one in which the temperature at depth remains near 22 °C. Euphausia diomedeae survived 1.6 kPa PO2 (∼22 µM O2) at 22 °C for the duration of six hour respiration experiments. Critical oxygen partial pressures were estimated for each species, and, for E. eximia, measured via oxygen consumption (2.1 kPa, 10 °C, n = 2) and lactate accumulation (1.1 kPa, 10 °C). A primary mechanism facilitating low oxygen tolerance is an ability to dramatically reduce energy expenditure during daytime forays into low oxygen waters. The ETP and Red Sea species reduced aerobic metabolism by more than 50% during exposure to hypoxia. Anaerobic glycolytic energy production, as indicated by whole-animal lactate accumulation, contributed only modestly to the energy deficit. Thus, the total metabolic rate was suppressed by ∼49–64%. Metabolic suppression during diel migrations to depth reduces the metabolic contribution of these species to vertical carbon and nitrogen flux (i.e., the biological pump) by an equivalent amount. Growing evidence suggests that metabolic suppression is a widespread strategy among migrating

Migraine induced by hypoxia

DEFF Research Database (Denmark)

Arngrim, Nanna; Schytz, Henrik Winther; Britze, Josefine

2016-01-01

in the visual cortex were measured by proton magnetic resonance spectroscopy. The circumference of cranial arteries was measured by 3 T high-resolution magnetic resonance angiography. Hypoxia induced migraine-like attacks in eight patients compared to one patient after sham (P = 0.039), aura in three...... and possible aura in 4 of 15 patients. Hypoxia did not change glutamate concentration in the visual cortex compared to sham, but increased lactate concentration (P = 0.028) and circumference of the cranial arteries (P ... suggests that hypoxia may provoke migraine headache and aura symptoms in some patients. The mechanisms behind the migraine-inducing effect of hypoxia should be further investigated....

Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?

Science.gov (United States)

Harrison, Louis; Blackwell, Kimberly

2004-01-01

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

On influencing factors of hypoxia in waters adjacent to the Changjiang estuary

Science.gov (United States)

Luo, Xiaofan; Wei, Hao; Fan, Renfu; Liu, Zhe; Zhao, Liang; Lu, Youyu

2018-01-01

Based on observational data from ten cruises carried out in 2012 and 2013, the distribution of dissolved oxygen (DO) and the evolution of hypoxia (DO concentrations induced by the spreading of the Changjiang Diluted Water (CDW), and developed into hypoxic zones due to lack of DO replenishment from the relatively DO-rich Yellow Sea Water and the KSW. The yearly evolution of hypoxia was influenced by shelf circulation especially the path of the KSW in the bottom layer of the water to the south of the Changjiang estuary, and the extension of the CDW in the surface layer over the Changjiang Bank.

Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

International Nuclear Information System (INIS)

Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin

2012-01-01

In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 μM SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: ► Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions ► Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia ► Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia ► Salicylic acid does not influence any of the investigated parameters under hypoxia

Hypoxia in the changing marine environment

International Nuclear Information System (INIS)

Zhang, J; Cowie, G; Naqvi, S W A

2013-01-01

The predicted future of the global marine environment, as a combined result of forcing due to climate change (e.g. warming and acidification) and other anthropogenic perturbation (e.g. eutrophication), presents a challenge to the sustainability of ecosystems from tropics to high latitudes. Among the various associated phenomena of ecosystem deterioration, hypoxia can cause serious problems in coastal areas as well as oxygen minimum zones in the open ocean (Diaz and Rosenberg 2008 Science 321 926–9, Stramma et al 2008 Science 320 655–8). The negative impacts of hypoxia include changes in populations of marine organisms, such as large-scale mortality and behavioral responses, as well as variations of species distributions, biodiversity, physiological stress, and other sub-lethal effects (e.g. growth and reproduction). Social and economic activities that are related to services provided by the marine ecosystems, such as tourism and fisheries, can be negatively affected by the aesthetic outcomes as well as perceived or real impacts on seafood quality (STAP 2011 (Washington, DC: Global Environment Facility) p 88). Moreover, low oxygen concentration in marine waters can have considerable feedbacks to other compartments of the Earth system, like the emission of greenhouse gases to the atmosphere, and can affect the global biogeochemical cycles of nutrients and trace elements. It is of critical importance to prediction and adaptation strategies that the key processes of hypoxia in marine environments be precisely determined and understood (cf Zhang et al 2010 Biogeosciences 7 1–24). (synthesis and review)

Tissue oxygenation in brain, muscle, and fat in a rat model of sleep apnea: differential effect of obstructive apneas and intermittent hypoxia.

Science.gov (United States)

Almendros, Isaac; Farré, Ramon; Planas, Anna M; Torres, Marta; Bonsignore, Maria R; Navajas, Daniel; Montserrat, Josep M

2011-08-01

To test the hypotheses that the dynamic changes in brain oxygen partial pressure (PtO(2)) in response to obstructive apneas or to intermittent hypoxia differ from those in other organs and that the changes in brain PtO(2) in response to obstructive apneas is a source of oxidative stress. Prospective controlled animal study. University laboratory. 98 Sprague-Dawley rats. Cerebral cortex, skeletal muscle, or visceral fat tissues were exposed in anesthetized animals subjected to either obstructive apneas or intermittent hypoxia (apneic and hypoxic events of 15 s each and 60 events/h) for 1 h. Arterial oxygen saturation (SpO(2)) presented a stable pattern, with similar desaturations during both stimuli. The PtO(2) was measured by a microelectrode. During obstructive apneas, a fast increase in cerebral PtO(2) was observed (38.2 ± 3.4 vs. 54.8 ± 5.9 mm Hg) but not in the rest of tissues. This particular cerebral response was not found during intermittent hypoxia. The cerebral content of reduced glutathione was decreased after obstructive apneas (46.2% ± 15.2%) compared to controls (100.0% ± 14.7%), but not after intermittent hypoxia. This antioxidant consumption after obstructive apneas was accompanied by increased cerebral lipid peroxidation under this condition. No changes were observed for these markers in the other tissues. These results suggest that cerebral cortex could be protected in some way from hypoxic periods caused by obstructive apneas. The increased cerebral PtO(2) during obstructive apneas may, however, cause harmful effects (oxidative stress). The obstructive apnea model appears to be more adequate than the intermittent hypoxia model for studying brain changes associated with OSA.

Effects of oxygen concentration on atmospheric pressure dielectric barrier discharge in Argon-Oxygen Mixture

Science.gov (United States)

Li, Xuechun; Li, Dian; Wang, Younian

2016-09-01

A dielectric barrier discharge (DBD) can generate a low-temperature plasma easily at atmospheric pressure and has been investigated for applications in trials in cancer therapy, sterilization, air pollution control, etc. It has been confirmed that reactive oxygen species (ROS) play a key role in the processes. In this work, we use a fluid model to simulate the plasma characteristics for DBD in argon-oxygen mixture. The effects of oxygen concentration on the plasma characteristics have been discussed. The evolution mechanism of ROS has been systematically analyzed. It was found that the ground state oxygen atoms and oxygen molecular ions are the dominated oxygen species under the considered oxygen concentrations. With the oxygen concentration increasing, the densities of electrons, argon atomic ions, resonance state argon atoms, metastable state argon atoms and excited state argon atoms all show a trend of decline. The oxygen molecular ions density is high and little influenced by the oxygen concentration. Ground state oxygen atoms density tends to increase before falling. The ozone density increases significantly. Increasing the oxygen concentration, the discharge mode begins to change gradually from the glow discharge mode to Townsend discharge mode. Project supported by the National Natural Science Foundation of China (Grant No. 11175034).

Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor.

Science.gov (United States)

Tarhonskaya, Hanna; Hardy, Adam P; Howe, Emily A; Loik, Nikita D; Kramer, Holger B; McCullagh, James S O; Schofield, Christopher J; Flashman, Emily

2015-08-07

The hypoxia-inducible factor (HIF) hydroxylases regulate hypoxia sensing in animals. In humans, they comprise three prolyl hydroxylases (PHD1-3 or EGLN1-3) and factor inhibiting HIF (FIH). FIH is an asparaginyl hydroxylase catalyzing post-translational modification of HIF-α, resulting in reduction of HIF-mediated transcription. Like the PHDs, FIH is proposed to have a hypoxia-sensing role in cells, enabling responses to changes in cellular O2 availability. PHD2, the most important human PHD isoform, is proposed to be biochemically/kinetically suited as a hypoxia sensor due to its relatively high sensitivity to changes in O2 concentration and slow reaction with O2. To ascertain whether these parameters are conserved among the HIF hydroxylases, we compared the reactions of FIH and PHD2 with O2. Consistent with previous reports, we found lower Km(app)(O2) values for FIH than for PHD2 with all HIF-derived substrates. Under pre-steady-state conditions, the O2-initiated FIH reaction is significantly faster than that of PHD2. We then investigated the kinetics with respect to O2 of the FIH reaction with ankyrin repeat domain (ARD) substrates. FIH has lower Km(app)(O2) values for the tested ARDs than HIF-α substrates, and pre-steady-state O2-initiated reactions were faster with ARDs than with HIF-α substrates. The results correlate with cellular studies showing that FIH is active at lower O2 concentrations than the PHDs and suggest that competition between HIF-α and ARDs for FIH is likely to be biologically relevant, particularly in hypoxic conditions. The overall results are consistent with the proposal that the kinetic properties of individual oxygenases reflect their biological capacity to act as hypoxia sensors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.

Science.gov (United States)

Vaupel, Peter; Mayer, Arnulf

Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue.

Feed intake and oxygen consumption in fish

NARCIS (Netherlands)

Subramanian, S.

2013-01-01

In fish, the voluntary feed intake is influenced by dietary, environmental and/or physiological factors. It is well known that under hypoxia the concentration of oxygen in the water (DO) determines the feed intake of fish. However at non-limiting water DO levels (normoxia), several other

Intramucosal–arterial PCO 2 gap fails to reflect intestinal dysoxia in hypoxic hypoxia

OpenAIRE

Dubin, Arnaldo; Murias, Gastón; Estenssoro, Elisa; Canales, Héctor; Badie, Julio; Pozo, Mario; Sottile, Juan P; Barán, Marcelo; Pálizas, Fernando; Laporte, Mercedes

2002-01-01

Introduction An elevation in intramucosal–arterial PCO 2 gradient (ΔPCO 2) could be determined either by tissue hypoxia or by reduced blood flow. Our hypothesis was that in hypoxic hypoxia with preserved blood flow, ΔPCO 2 should not be altered. Methods In 17 anesthetized and mechanically ventilated sheep, oxygen delivery was reduced by decreasing flow (ischemic hypoxia, IH) or arterial oxygen saturation (hypoxic hypoxia, HH), or no intervention was made (sham). In the IH group (n = 6), blood...

Rational use of oxygen in medical disease and anesthesia

DEFF Research Database (Denmark)

Meyhoff, Christian S; Staehr, Anne K; Rasmussen, Lars S

2012-01-01

Supplemental oxygen is often administered during anesthesia and in critical illness to treat hypoxia, but high oxygen concentrations are also given for a number of other reasons such as prevention of surgical site infection (SSI). The decision to use supplemental oxygen is, however, controversial......, because of large heterogeneity in the reported results and emerging reports of side-effects. The aim of this article is to review the recent findings regarding benefits and harms of oxygen therapy in anesthesia and acute medical conditions....

A method for measuring brain partial pressure of oxygen in unanesthetized unrestrained subjects: the effect of acute and chronic hypoxia on brain tissue PO(2).

Science.gov (United States)

Ortiz-Prado, E; Natah, Siraj; Srinivasan, Sathyanarayanan; Dunn, Jeff F

2010-11-30

The level of tissue oxygenation provides information related to the balance between oxygen delivery, oxygen utilization, tissue reactivity and morphology during physiological conditions. Tissue partial pressure of oxygen (PtO(2)) is influenced by the use of anesthesia or restraint. These factors may impact the absolute level of PtO(2). In this study we present a novel fiber optic method to measure brain PtO(2). This method can be used in unanesthetized, unrestrained animals, provides absolute values for PO(2), has a stable calibration, does not consume oxygen and is MRI compatible. Brain PtO(2) was studied during acute hypoxia, as well as before and after 28 days of high altitude acclimatization. A sensor was chronically implanted in the frontal cortex of eight Wistar rats. It is comprised of a fiber optic probe with a tip containing material that fluoresces with an oxygen dependent lifetime. Brain PtO(2) declines by 80% and 76% pre- and post-acclimatization, respectively, when the fraction of inspired oxygen declines from 0.21 to 0.08. In addition, a linear relationship between brain PtO(2) and inspired O(2) levels was demonstrated r(2)=0.98 and r(2)=0.99 (pre- and post-acclimatization). Hypoxia acclimatization resulted in an increase in the overall brain PtO(2) by approximately 35%. This paper demonstrates the use of a novel chronically implanted fiber optic based sensor for measuring absolute PtO(2). It shows a very strong linear relationship in awake animals between inspired O(2) and tissue O(2), and shows that there is a proportional increase in PtO(2) over a range of inspired values after exposure to chronic hypoxia. Copyright © 2010 Elsevier B.V. All rights reserved.

Simultaneous Hypoxia and Low Extracellular pH Suppress Overall Metabolic Rate and Protein Synthesis In Vitro.

Directory of Open Access Journals (Sweden)

Brita Singers Sørensen

Full Text Available The tumor microenvironment is characterized by regions of hypoxia and acidosis which are linked to poor prognosis. This occurs due to an aberrant vasculature as well as high rates of glycolysis and lactate production in tumor cells even in the presence of oxygen (the Warburg effect, which weakens the spatial linkage between hypoxia and acidosis.Five different human squamous cell carcinoma cell lines (SiHa, FaDuDD, UTSCC5, UTSCC14 and UTSCC15 were treated with hypoxia, acidosis (pH 6.3, or a combination, and gene expression analyzed using microarray. SiHa and FaDuDD were chosen for further characterization of cell energetics and protein synthesis. Total cellular ATP turnover and relative glycolytic dependency was determined by simultaneous measurements of oxygen consumption and lactate synthesis rates and total protein synthesis was determined by autoradiographic quantification of the incorporation of 35S-labelled methionine and cysteine into protein.Microarray analysis allowed differentiation between genes induced at low oxygen only at normal extracellular pH (pHe, genes induced at low oxygen at both normal and low pHe, and genes induced at low pHe independent of oxygen concentration. Several genes were found to be upregulated by acidosis independent of oxygenation. Acidosis resulted in a more wide-scale change in gene expression profiles than hypoxia including upregulation of genes involved in the translation process, for example Eukaryotic translation initiation factor 4A, isoform 2 (EIF4A2, and Ribosomal protein L37 (RPL37. Acidosis suppressed overall ATP turnover and protein synthesis by 50%. Protein synthesis, but not total ATP production, was also suppressed under hypoxic conditions. A dramatic decrease in ATP turnover (SiHa and protein synthesis (both cell lines was observed when hypoxia and low pHe were combined.We demonstrate here that the influence of hypoxia and acidosis causes different responses, both in gene expression and in de

Short-term alteration of biotic and abiotic components of the pelagic system in a shallow bay produced by a strong natural hypoxia event

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Veas, Rodrigo; Anabalón, Valeria; Quiñones, Renato A.

2017-01-01

In January 2008 there was an intensive and extensive upwelling event in the southern Humboldt Current System. This event produced an intrusion of water with low dissolved oxygen into Coliumo Bay, which caused massive mortality and the beaching of pelagic and benthic organisms, including zooplankton. During this event, which lasted 3 to 5 days, we studied and evaluated the effect of the hypoxic water in the bay on the abundance of macrozooplankton, nanoplankton and microphytoplankton, the concentration of several nutrients and hydrographic conditions. At the beginning of the hypoxia event the water column had very low dissolved oxygen concentrations (oxygen minimum zone from the Humboldt Current System. Redox, pH, nitrate, phosphate, silicate and chlorophyll-a values were the lowest, while nitrate and the phaeopigment values were the highest. The N:P ratio was below 16, and the abundance of nano- and microphytoplankton were at their lowest, the latter also with the lowest proportion of live organisms. Macrozooplankton had the greatest abundance during hypoxia, dominated mainly by crustacean, fish eggs and amphipods. The hypoxia event generated a strong short-term alteration of all biotic and abiotic components of the pelagic system in Coliumo Bay and the neighboring coastal zone. These negative effects associated with strong natural hypoxia events could have important consequences for the productivity and ecosystem functioning of the coastal zone of the Humboldt Current System if, as suggested by several models, winds favorable to upwelling should increase due to climate change. The effects of natural hypoxia in this coastal zone can be dramatic especially for pelagic and benthic species not adapted to endure conditions of low dissolved oxygen. PMID:28715447

Zooplankton Distribution and Species Composition Along an Oxygen Gradient in Puget Sound, WA

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Keister, J. E.; Essington, T.; Li, L.; Horne, J. K.; Sato, M.; Parker-Stetter, S. L.; Moriarty, P.

2016-02-01

Low dissolved oxygen (hypoxia) is one of the most pronounced, pervasive, and significant disturbances in marine ecosystems, yet our understanding of its effects is incomplete, particularly with respect to impacts on lower trophic levels. As part of a study of how hypoxia affects predator-prey relationships and energy flow through marine food webs, we are studying relationships between ocean chemistry and zooplankton in Puget Sound, Washington—a deep, seasonally hypoxic fjord in the Pacific Northwest that supports a productive and diverse pelagic community. From summer through fall in two years that differed in the timing and intensity of hypoxia, we conducted multi-frequency bioacoustic surveys, CTD casts, and depth-stratified zooplankton sampling to examine changes in distribution and species composition of animals in relation to oxygen concentrations. We exploited a natural gradient in oxygen along the axis of the fjord by sampling at moderately hypoxic and normoxic sites with otherwise similar hydrography and species composition to disentangle the effects of oxygen from changes in other environmental factors. Our results support the hypothesis that zooplankton species composition and vertical distributions are altered by hypoxia, but only when examined at the species and life-stage level. Relatively few taxa showed clear responses to hypoxia, and bioacoustic backscatter data (which was dominated by adult euphausiids and amphipods) indicated that those taxa were not affected by the levels of hypoxia we observed. Examination of net tow data revealed more subtle changes, including behavioral avoidance of low oxygen by some copepods and young euphausiid life stages. Overall, the high species diversity and relatively low susceptibility of many zooplankton to hypoxia in Puget Sound may confer ecosystem resilience to near-future projected changes in this region.

Aquatic respiration rate measurements at low oxygen concentrations.

Directory of Open Access Journals (Sweden)

Moritz Holtappels

Full Text Available Despite its huge ecological importance, microbial oxygen respiration in pelagic waters is little studied, primarily due to methodological difficulties. Respiration measurements are challenging because of the required high resolution of oxygen concentration measurements. Recent improvements in oxygen sensing techniques bear great potential to overcome these limitations. Here we compare 3 different methods to measure oxygen consumption rates at low oxygen concentrations, utilizing amperometric Clark type sensors (STOX, optical sensors (optodes, and mass spectrometry in combination with (18-18O2 labeling. Oxygen concentrations and consumption rates agreed well between the different methods when applied in the same experimental setting. Oxygen consumption rates between 30 and 400 nmol L(-1 h(-1 were measured with high precision and relative standard errors of less than 3%. Rate detection limits in the range of 1 nmol L(-1 h(-1 were suitable for rate determinations in open ocean water and were lowest at the lowest applied O2 concentration.

The Deepwater Horizon oil spill and Gulf of Mexico shelf hypoxia

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Rabalais, Nancy N.; Smith, Leslie M.; Turner, R. Eugene

2018-01-01

The oil/water/dispersant mixture from the 2010 Deepwater Horizon oil spill was juxtaposed on the Louisiana continental shelf with the annual development of oxygen-depleted bottom waters. There was uncertainty whether the oil from the spill might worsen the extent or severity of the seasonal hypoxic area formation in 2010. The surface and bottom water hydrocarbons in May were elevated compared to in June and July, while the bottom-water dissolved oxygen concentrations were higher in May and June compared to in July. The degradation of oil in the water column or sediments was not known. The results of an empirical orthogonal functions (EOF) analysis of the progression of hypoxia development in May, June and July 2010, and an analysis of conditions in July compared to a 27-year background database, indicated no difference in oxygen concentrations for May, June or July 2010, with or without oil data included, nor any difference in July 2010 compared to other years. The analysis instead indicated that, in all years compared, the hypoxic area increased with higher river discharge, higher nitrate-N load, an easterly (westward) wind and reduced wind speed. Although the analyses did not demonstrate that the oil spill affected, or did not affect, the size of the 2010 hypoxic zone, there was evidence that the 2010 hypoxia season did not differ from the long-term record.

Contrasting effects of hypoxia on copper toxicity during development in the three-spined stickleback (Gasterosteus aculeatus).

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Fitzgerald, Jennifer A; Katsiadaki, Ioanna; Santos, Eduarda M

2017-03-01

Hypoxia is a global problem in aquatic systems and often co-occurs with pollutants. Despite this, little is known about the combined effects of these stressors on aquatic organisms. The objective of this study was to investigate the combined effects of hypoxia and copper, a toxic metal widespread in the aquatic environment. We used the three-spined stickleback (Gasterosteus aculeatus) as a model because of its environmental relevance and amenability for environmental toxicology studies. We focused on embryonic development as this is considered to be a sensitive life stage to environmental pollution. We first investigated the effects of hypoxia alone on stickleback development to generate the information required to design subsequent studies. Our data showed that exposure to low oxygen concentrations (24.7 ± 0.9% air saturation; AS) resulted in strong developmental delays and increased mortalities, whereas a small decrease in oxygen (75.0 ± 0.5%AS) resulted in premature hatching. Stickleback embryos were then exposed to a range of copper concentrations under hypoxia (56.1 ± 0.2%AS) or normoxia (97.6 ± 0.1%AS), continuously, from fertilisation to free swimming larvae. Hypoxia caused significant changes in copper toxicity throughout embryonic development. Prior to hatching, hypoxia suppressed the occurrence of mortalities, but after hatching hypoxia significantly increased copper toxicity. Interestingly, when exposures were conducted only after hatching, the onset of copper-induced mortalities was delayed under hypoxia compared to normoxia, but after 48 h, copper was more toxic to hatched embryos under hypoxia. This is the second species for which the protective effect of hypoxia on copper toxicity prior to hatching, followed by its exacerbating effect after hatching is demonstrated, suggesting the hypothesis that this pattern may be common for teleost species. Our research highlights the importance of considering the interactions between multiple

Optimized chondrogenesis of ATCD5 cells through sequential regulation of oxygen conditions

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Chen, Li; Fink, Trine; Ebbesen, Peter

2006-01-01

, chondrocyte-specific extracellular matrix (ECM) production was monitored. Furthermore, the transcription of collagen II, an early-phase marker, and collagen X, a marker of hypertrophic conversion, was followed by real-time RT-PCR. Low oxygen concentrations between 1 and 9% inhibited chondrogenic conversion......, as evidenced by reduced glycosaminoglycan deposition in the ECM in a manner proportional to the degree of hypoxia. Cells cultured at oxygen concentrations of 12 and 15% underwent a faster and higher degree of early-phase chondrogenesis when compared to control cells cultured at ambient air (21% O2......). For the hypertrophic conversion of the ATDC5 cells, all degrees of hypoxia inhibited collagen X expression in a dose-dependent manner. Short-term culturing of the ATDC5 cells for 6 to 8 days at 12% oxygen with subsequent culturing at 21% for the remainder of the experiment resulted in maximal production of major ECM...

Direct measurement of local oxygen concentration in the bone marrow of live animals

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Spencer, Joel A.; Ferraro, Francesca; Roussakis, Emmanuel; Klein, Alyssa; Wu, Juwell; Runnels, Judith M.; Zaher, Walid; Mortensen, Luke J.; Alt, Clemens; Turcotte, Raphaël; Yusuf, Rushdia; Côté, Daniel; Vinogradov, Sergei A.; Scadden, David T.; Lin, Charles P.

2014-04-01

Characterization of how the microenvironment, or niche, regulates stem cell activity is central to understanding stem cell biology and to developing strategies for the therapeutic manipulation of stem cells. Low oxygen tension (hypoxia) is commonly thought to be a shared niche characteristic in maintaining quiescence in multiple stem cell types. However, support for the existence of a hypoxic niche has largely come from indirect evidence such as proteomic analysis, expression of hypoxia inducible factor-1α (Hif-1α) and related genes, and staining with surrogate hypoxic markers (for example, pimonidazole). Here we perform direct in vivo measurements of local oxygen tension (pO2) in the bone marrow of live mice. Using two-photon phosphorescence lifetime microscopy, we determined the absolute pO2 of the bone marrow to be quite low (hypoxic as it is perfused with small arteries that are often positive for the marker nestin. These pO2 values change markedly after radiation and chemotherapy, pointing to the role of stress in altering the stem cell metabolic microenvironment.

Short- and long-term behavioral effects of exposure to 21%, 40% and 100% oxygen after perinatal hypoxia-ischemia in the rat.

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Woodworth, K Nina; Palmateer, Julie; Swide, Joseph; Grafe, Marjorie R

2011-10-01

Until recently, supplementation with 100% oxygen was standard therapy for newborns who required resuscitation at birth or suffered later hypoxic-ischemic events. Exposure to high concentrations of oxygen, however, may worsen oxidative stress induced by ischemic injury. In this study we investigated the short- and long-term behavioral outcomes in rats that had undergone hypoxic-ischemic brain injury on postnatal day 7, followed by 2h exposure to 21%, 40%, or 100% oxygen, compared to normal controls. There were no differences in the development of walking, head lifting and righting reflexes from postnatal days 9 to 15. Cliff avoidance showed some abnormal responses in the H21 animals. From postnatal days 28 to 56, three tests of sensorimotor coordination were performed weekly: ledged tapered beam, cylinder, and bilateral tactile stimulation. The ledged tapered beam test without prior training of animals was sensitive to injury, but did not distinguish between treatment groups. The cylinder test showed a greater use of the unimpaired limb in female 21% and 40% oxygen groups compared to controls. Performance in both cylinder and the beam tests showed a correlation with the degree of brain injury. The bilateral tactile stimulation test showed that the male 21% oxygen groups had worse sensory asymmetry than male 40% or 100% oxygen groups, but was not statistically significantly different from controls. We thus found a minor benefit to post-hypoxia-ischemic treatment with 100% and 40% oxygen compared to 21% in one test of early motor skills. Our results for long-term sensorimotor behavior, however, showed conflicting results, however, as males treated with 40% or 100% oxygen had less sensory asymmetry (better performance) in the bilateral tactile stimulation test than males treated with 21% oxygen, while females had impaired motor performance in the cylinder test with both 21% and 40% oxygen. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro.

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McCord, Amy M; Jamal, Muhammad; Shankavaram, Uma T; Shankavarum, Uma T; Lang, Frederick F; Camphausen, Kevin; Tofilon, Philip J

2009-04-01

In vitro investigations of tumor stem-like cells (TSC) isolated from human glioblastoma (GB) surgical specimens have been done primarily at an atmospheric oxygen level of 20%. To determine whether an oxygen level more consistent with in situ conditions affects their stem cell-like characteristics, we compared GB TSCs grown under conditions of 20% and 7% oxygen. Growing CD133(+) cells sorted from three GB neurosphere cultures at 7% O(2) reduced their doubling time and increased the self-renewal potential as reflected by clonogenicity. Furthermore, at 7% oxygen, the cultures exhibited an enhanced capacity to differentiate along both the glial and neuronal pathways. As compared with 20%, growth at 7% oxygen resulted in an increase in the expression levels of the neural stem cell markers CD133 and nestin as well as the stem cell markers Oct4 and Sox2. In addition, whereas hypoxia inducible factor 1alpha was not affected in CD133(+) TSCs grown at 7% O(2), hypoxia-inducible factor 2alpha was expressed at higher levels as compared with 20% oxygen. Gene expression profiles generated by microarray analysis revealed that reducing oxygen level to 7% resulted in the up-regulation and down-regulation of a significant number of genes, with more than 140 being commonly affected among the three CD133(+) cultures. Furthermore, Gene Ontology categories up-regulated at 7% oxygen included those associated with stem cells or GB TSCs. Thus, the data presented indicate that growth at the more physiologically relevant oxygen level of 7% enhances the stem cell-like phenotype of CD133(+) GB cells.

Effects of hypoxia on human cancer cell line chemosensitivity

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2013-01-01

Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

Kinetic modeling in PET imaging of hypoxia

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Li, Fan; Joergensen, Jesper T; Hansen, Anders E; Kjaer, Andreas

2014-01-01

Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can be used for non-invasive mapping of tissue oxygenation in vivo and several hypoxia specific PET tracers have been developed. Evaluation of PET data in the clinic is commonly based on visual assessment together with semiquantitative measurements e.g. standard uptake value (SUV). However, dynamic PET contains additional valuable information on the temporal changes in tracer distribution. Kinetic modeling can be used to extract relevant pharmacokinetic parameters of tracer behavior in vivo that reflects relevant physiological processes. In this paper, we review the potential contribution of kinetic analysis for PET imaging of hypoxia. PMID:25250200

Comparative evaluation of diffusion hypoxia and psychomotor skills with or without postsedation oxygenation following administration of nitrous oxide in children undergoing dental procedures: A clinical study.

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Khinda, Vineet Inder Singh; Bhuria, Parvesh; Khinda, Paramjit; Kallar, Shiminder; Brar, Gurlal Singh

2016-01-01

Diffusion hypoxia is the most serious potential complication associated with nitrous oxide. It occurs during the recovery period. Hence, administration of 100% oxygen is mandatory as suggested by many authors. The aim of this study is to evaluate the occurrence/nonoccurrence of diffusion hypoxia in two groups of patients undergoing routine dental treatment under nitrous oxide sedation when one group is subjected to 7 min of postsedation oxygenation and the second group of the patients is made to breathe room air for the similar period. A total of sixty patients within the age group of 7-10 years requiring invasive dental procedures were randomly divided into two groups of 30 each using chit method. In the control group, patients were administered 100% oxygen postsedation, whereas, in the study group, patients were made to breathe room air postsedation. Various parameters (pulse rate, respiratory rate, blood pressure, and oxygen saturation [SpO2]) were recorded pre- and post-operatively. Data were collected and then sent for statistical analysis. The mean postoperative SpO2 at measurement times 1, 3, 5, and 7 min in both the groups was higher than the mean preoperative SpO2. This increase was statistically significant. No significant difference was found between the Trieger test scores. This study proves that clinical occurrence of diffusion hypoxia is not possible while following the routine procedure of nitrous oxide sedation.

Progressive hypoxia decouples activity and aerobic performance of skate embryos.

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Di Santo, Valentina; Tran, Anna H; Svendsen, Jon C

2016-01-01

Although fish population size is strongly affected by survival during embryonic stages, our understanding of physiological responses to environmental stressors is based primarily on studies of post-hatch fishes. Embryonic responses to acute exposure to changes in abiotic conditions, including increase in hypoxia, could be particularly important in species exhibiting long developmental time, as embryos are unable to select a different environment behaviourally. Given that oxygen is key to metabolic processes in fishes and aquatic hypoxia is becoming more severe and frequent worldwide, organisms are expected to reduce their aerobic performance. Here, we examined the metabolic and behavioural responses of embryos of a benthic elasmobranch fish, the little skate (Leucoraja erinacea), to acute progressive hypoxia, by measuring oxygen consumption and movement (tail-beat) rates inside the egg case. Oxygen consumption rates were not significantly affected by ambient oxygen levels until reaching 45% air saturation (critical oxygen saturation, S crit). Below S crit, oxygen consumption rates declined rapidly, revealing an oxygen conformity response. Surprisingly, we observed a decoupling of aerobic performance and activity, as tail-beat rates increased, rather than matching the declining metabolic rates, at air saturation levels of 55% and below. These results suggest a significantly divergent response at the physiological and behavioural levels. While skate embryos depressed their metabolic rates in response to progressive hypoxia, they increased water circulation inside the egg case, presumably to restore normoxic conditions, until activity ceased abruptly around 9.8% air saturation.

[The level of superoxide dismutase expression in primary and metastatic colorectal cancer cells in hypoxia and tissue normoxia].

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Skrzycki, Michał; Czeczot, Hanna; Chrzanowska, Alicja; Otto-Ślusarczyk, Dagmara

2015-11-01

Superoxide oxidase (SOD) is a key antioxidant enzyme protecting cells against oxidative stress, which might induce cancerogenesis. In tumor cells SOD influences the level of the reactive oxygen species (ROS) allowing for survival and proliferation. High rate of cells proliferation in tumor leads to their temporary hypoxia due to lower rate of angiogenesis. Therefore during tumor development, cancer cells function in conditions of hypoxia or tissue normoxia. The aim of study was to evaluate of SOD isoenzymes (SOD1 and SOD2) expression level in cell lines of primary (SW 480) and metastatic (SW 620) colorectal cancer, cultured in hypoxia (1% oxygen), tissue normoxia (10% oxygen), and atmospheric normoxia (21% oxygen). Cells were cultured in MEM medium in different oxygen concentrations (1%, 10%, 21%) in hypoxic chamber with oxygenation regulator. The number of living cells in lines SW 480 and 620 was determined by trypan blue method. Expression of SOD1 and SOD2 at the mRNA level was determined by RT-PCR and PCR. In both studied cell lines (SW 480 and SW 620), the number of living cells (viability) was increased in hypoxia and atmospheric normoxia. The expression level of SOD1 and SOD2 in studied cell lines was different. The lowest level of expression of both SOD isoenzymes was observed in hypoxia. In conditions of atmospheric normoxia the expression level of SOD1 in SW480 cell line was increased, and similar in SW620 cell line comparing to tissue normoxia. Whereas the SOD2 expression level in atmospheric normoxia conditions in both cell lines was significantly increased. Observed differences were statistically significant (p ≤ 0,05). The profile of expression of SOD1 and SOD2 in cell lines SW480 and SW620 indicates differentiated response of tumor cells depending on access to oxygen. Low level of SOD isoenzymes expression in SW480 and SW620 cells in hypoxia indicates decreased production of ROS. Differences of SOD isoenzymes expression level in tissue normoxia

Cellular Oxygen Sensing: Crystal Structure of Hypoxia-Inducible Factor Prolyl Hydroxylase (PHD2)

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McDonough,M.; Li, V.; Flashman, E.; Chowdhury, R.; Mohr, C.; Lienard, B.; Zondlo, J.; Oldham, N.; Clifton, I.; et al.

2006-01-01

Cellular and physiological responses to changes in dioxygen levels in metazoans are mediated via the posttranslational oxidation of hypoxia-inducible transcription factor (HIF). Hydroxylation of conserved prolyl residues in the HIF-{alpha} subunit, catalyzed by HIF prolyl-hydroxylases (PHDs), signals for its proteasomal degradation. The requirement of the PHDs for dioxygen links changes in dioxygen levels with the transcriptional regulation of the gene array that enables the cellular response to chronic hypoxia; the PHDs thus act as an oxygen-sensing component of the HIF system, and their inhibition mimics the hypoxic response. We describe crystal structures of the catalytic domain of human PHD2, an important prolyl-4-hydroxylase in the human hypoxic response in normal cells, in complex with Fe(II) and an inhibitor to 1.7 Angstroms resolution. PHD2 crystallizes as a homotrimer and contains a double-stranded {beta}-helix core fold common to the Fe(II) and 2-oxoglutarate-dependant dioxygenase family, the residues of which are well conserved in the three human PHD enzymes (PHD 1-3). The structure provides insights into the hypoxic response, helps to rationalize a clinically observed mutation leading to familial erythrocytosis, and will aid in the design of PHD selective inhibitors for the treatment of anemia and ischemic disease.

Hypoxia-inducible factor-1 alpha has a key role in hypoxic preconditioning.

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Taie, Satoshi; Ono, Junichiro; Iwanaga, Yasuyuki; Tomita, Shuhei; Asaga, Takehiko; Chujo, Kosuke; Ueki, Masaaki

2009-08-01

Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.

Chondroprotective effect of zinc oxide nanoparticles in conjunction with hypoxia on bovine cartilage-matrix synthesis.

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Mirza, Eraj Humayun; Pan-Pan, Chong; Wan Ibrahim, Wan Mohd Azhar Bin; Djordjevic, Ivan; Pingguan-Murphy, Belinda

2015-11-01

Articular cartilage is a tissue specifically adapted to a specific niche with a low oxygen tension (hypoxia), and the presence of such conditions is a key factor in regulating growth and survival of chondrocytes. Zinc deficiency has been linked to cartilage-related disease, and presence of Zinc is known to provide antibacterial benefits, which makes its inclusion attractive in an in vitro system to reduce infection. Inclusion of 1% zinc oxide nanoparticles (ZnONP) in poly octanediol citrate (POC) polymer cultured in hypoxia has not been well determined. In this study we investigated the effects of ZnONP on chondrocyte proliferation and matrix synthesis cultured under normoxia (21% O2 ) and hypoxia (5% O2 ). We report an upregulation of chondrocyte proliferation and sulfated glycosaminoglycan (S-GAG) in hypoxic culture. Results demonstrate a synergistic effect of oxygen concentration and 1% ZnONP in up-regulation of anabolic gene expression (Type II collagen and aggrecan), and a down regulation of catabolic (MMP-13) gene expression. Furthermore, production of transcription factor hypoxia-inducible factor 1A (HIF-1A) in response to hypoxic condition to regulate chondrocyte survival under hypoxia is not affected by the presence of 1% ZnONP. Presence of 1% ZnONP appears to act to preserve homeostasis of cartilage in its hypoxic environment. © 2015 Wiley Periodicals, Inc.

Plankton community respiration, net ecosystem metabolism, and oxygen dynamics on the Louisiana continental shelf: Implications for hypoxia

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Murrell, Michael C.; Stanley, Roman S.; Lehrter, John C.; Hagy, James D.

2013-01-01

We conducted a multi-year study of the Louisiana continental shelf (LCS) to better understand the linkages between water column metabolism and the formation of hypoxia (dissolved oxygen Continental Shelf Research, 29: 1861-1872) to estimate net water column metabolism. There was consistent evidence of net heterotrophy, particularly in western transects, and in deeper waters (>40 m depth), indicating a net organic carbon deficit on the LCS. We offer a simple scale argument to suggest that riverine and inshore coastal waters may be significant sources of organic carbon to account for this deficit. This study provided unprecedented, continental shelf scale coverage of heterotrophic metabolism, which is useful for constraining models of oxygen, carbon, and nutrient dynamics along the LCS.

Modulation of radioprotective effects of respiratory hypoxia by changing the duration of hypoxia before irradiation and by combining hypoxia and administration of hemopoiesis-stimulating agents

International Nuclear Information System (INIS)

Vacek, A.; Hofer, M.

2001-01-01

Aim: Analysis of radioprotective effect of respiratory hypoxia on hemopoietic tissue and enhancement of this effect by hemopoietic activation. Material and methods: In mice breathing hypoxic gas mixture during total body gamma irradiation the recovery of pluripotent and committed granulocyte-macrophage progenitor cells and animal lethality were determined. Results: In mice forced to breathe 10% O 2 and 8% O 2 during irradiation, the oxygen tension in the spleen decreased to 40% and 20%, respectively, of control values. Hypoxia mitigated the lethal effect of gamma-rays and improved the recovery of hemopoiesis in compartments of pluripotent and committed progenitor cells. Enhancement of the proliferative activity in hemopoietic tissue by a cytokine (rmGM-CSF) or an immunomodulator (dextran sulfate) increased the effect of hypoxic radioprotection, while elimination of proliferative cells by hydroxyurea decreased the radioprotective effect. Adaptation of experimental animals to hypoxic conditions was found to reduce the radioprotective effect without influencing tissue partial oxygen pressure lowered by hypoxic conditions. Conclusion: The data presented confirm the radioprotective effect of 10% and 8% O 2 respiratory hypoxia on hemopoiesis. These findings may represent a way out for further experimental and clinical research aimed at considering differential protection of various tissues by hypoxia. (orig.) [de

Hypoxia inhibits hypertrophic differentiation and endochondral ossification in explanted tibiae.

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Jeroen C H Leijten

Full Text Available Hypertrophic differentiation of growth plate chondrocytes induces angiogenesis which alleviates hypoxia normally present in cartilage. In the current study, we aim to determine whether alleviation of hypoxia is merely a downstream effect of hypertrophic differentiation as previously described or whether alleviation of hypoxia and consequent changes in oxygen tension mediated signaling events also plays an active role in regulating the hypertrophic differentiation process itself.Fetal mouse tibiae (E17.5 explants were cultured up to 21 days under normoxic or hypoxic conditions (21% and 2.5% oxygen respectively. Tibiae were analyzed on growth kinetics, histology, gene expression and protein secretion.The oxygen level had a strong influence on the development of explanted fetal tibiae. Compared to hypoxia, normoxia increased the length of the tibiae, length of the hypertrophic zone, calcification of the cartilage and mRNA levels of hypertrophic differentiation-related genes e.g. MMP9, MMP13, RUNX2, COL10A1 and ALPL. Compared to normoxia, hypoxia increased the size of the cartilaginous epiphysis, length of the resting zone, calcification of the bone and mRNA levels of hyaline cartilage-related genes e.g. ACAN, COL2A1 and SOX9. Additionally, hypoxia enhanced the mRNA and protein expression of the secreted articular cartilage markers GREM1, FRZB and DKK1, which are able to inhibit hypertrophic differentiation.Collectively our data suggests that oxygen levels play an active role in the regulation of hypertrophic differentiation of hyaline chondrocytes. Normoxia stimulates hypertrophic differentiation evidenced by the expression of hypertrophic differentiation related genes. In contrast, hypoxia suppresses hypertrophic differentiation of chondrocytes, which might be at least partially explained by the induction of GREM1, FRZB and DKK1 expression.

Investigation of hypoxia off the Changjiang Estuary using a coupled model of ROMS-CoSiNE

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Zhou, Feng; Chai, Fei; Huang, Daji; Xue, Huijie; Chen, Jianfang; Xiu, Peng; Xuan, Jiliang; Li, Jia; Zeng, Dingyong; Ni, Xiaobo; Wang, Kui

2017-12-01

The cause for large variability of hypoxia off the Changjiang Estuary has not been well understood partly due to various nutrient sources and complex physical-biological processes involved. The Regional Ocean Modeling Systems (ROMS) coupled with Carbon, Silicate and Nitrogen Ecosystem (CoSiNE) was used to investigate the 2006 hypoxia in the East China Sea, the largest hypoxia ever recorded. The model performance was evaluated comprehensively by comparing a suite of quantitative metrics, procedures and spatiotemporal patterns between the simulated results and observed data. The simulated results are generally consistent with the observations and are capable of reproducing the development of hypoxia and the observed vertical profiles of dissolved oxygen. Event-scale reduction of hypoxia occurred during the weakening of stratification in mid-July and mid-September, due to strong stirring caused by tropical storms or strong northerly wind. Change in wind direction altered the pathway of Changjiang Diluted Water and consequently caused variation in hypoxic location. Increase in river discharge led to an expansion of hypoxic water during the summer monsoon. Sensitivity analysis suggested that the hypoxia extent was affected by the change in nutrient concentration of the Changjiang as well as that of the Kuroshio. Sensitivity analysis also suggested the importance of sediment oxygen consumption to the size of the hypoxic zone. These results demonstrate that a prognostic 3D model is useful for investigating the highly variable hypoxia, with comprehensive considerations of multiple factors related to both physical and biological processes from the estuary to the shelf break of the East China Sea.

Low oxygen atmosphere facilitates proliferation and maintains undifferentiated state of umbilical cord mesenchymal stem cells in an hypoxia inducible factor-dependent manner.

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Drela, Katarzyna; Sarnowska, Anna; Siedlecka, Patrycja; Szablowska-Gadomska, Ilona; Wielgos, Miroslaw; Jurga, Marcin; Lukomska, Barbara; Domanska-Janik, Krystyna

2014-07-01

As we approach the era of mesenchymal stem cell (MSC) application in the medical clinic, the standarization of their culture conditions are of the particular importance. We re-evaluated the influences of oxygens concentration on proliferation, stemness and differentiation of human umbilical cord Wharton Jelly-derived MSCs (WJ-MSCs). Primary cultures growing in 21% oxygen were either transferred into 5% O2 or continued to grow under standard 21% oxygen conditions. Cell expansion was estimated by WST1/enzyme-linked immunosorbent assay or cell counting. After 2 or 4 weeks of culture, cell phenotypes were evaluated using microscopic, immunocytochemical, fluorescence-activated cell-sorting and molecular methods. Genes and proteins typical of mesenchymal cells, committed neural cells or more primitive stem/progenitors (Oct4A, Nanog, Rex1, Sox2) and hypoxia inducible factor (HIF)-1α-3α were evaluated. Lowering O2 concentration from 21% to the physiologically relevant 5% level substantially affected cell characteristics, with induction of stemness-related-transcription-factor and stimulation of cell proliferative capacity, with increased colony-forming unit fibroblasts (CFU-F) centers exerting OCT4A, NANOG and HIF-1α and HIF-2α immunoreactivity. Moreover, the spontaneous and time-dependent ability of WJ-MSCs to differentiate into neural lineage under 21% O2 culture was blocked in the reduced oxygen condition. Importantly, treatment with trichostatin A (TSA, a histone deacetylase inhibitor) suppressed HIF-1α and HIF-2α expression, in addition to blockading the cellular effects of reduced oxygen concentration. A physiologically relevant microenvironment of 5% O2 rejuvenates WJ-MSC culture toward less-differentiated, more primitive and faster-growing phenotypes with involvement of HIF-1α and HIF-2α-mediated and TSA-sensitive chromatin modification mechanisms. These observations add to the understanding of MSC responses to defined culture conditions, which is the most

Cognitive responses to hypobaric hypoxia: implications for aviation training

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Neuhaus C

2014-11-01

Full Text Available Christopher Neuhaus,1,2 Jochen Hinkelbein2,31Department of Anesthesiology, Heidelberg University Hospital, Ruprecht Karls University of Heidelberg, Heidelberg, 2Emergency Medicine and Air Rescue Working Group, German Society of Aviation and Space Medicine (DGLRM, Munich, 3Department of Anesthesiology and Intensive Care Medicine, University Hospital of Cologne, Cologne, GermanyAbstract: The aim of this narrative review is to provide an overview on cognitive responses to hypobaric hypoxia and to show relevant implications for aviation training. A principal element of hypoxia-awareness training is the intentional evocation of hypoxia symptoms during specific training sessions within a safe and controlled environment. Repetitive training should enable pilots to learn and recognize their personal hypoxia symptoms. A time span of 3–6 years is generally considered suitable to refresh knowledge of the more subtle and early symptoms especially. Currently, there are two different technical approaches available to induce hypoxia during training: hypobaric chamber training and reduced-oxygen breathing devices. Hypoxia training for aircrew is extremely important and effective, and the hypoxia symptoms should be emphasized clearly to aircrews. The use of tight-fitting masks, leak checks, and equipment checks should be taught to all aircrew and reinforced regularly. It is noteworthy that there are major differences in the required quality and quantity of hypoxia training for both military and civilian pilots.Keywords: cognitive response, aviation training, pilot, hypoxia, oxygen, loss of consciousness

Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia

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Richard T. Jaspers

2014-07-01

Full Text Available Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH (10% air/90%N2 saturated water. We analyzed cross-sectional area (CSA, succinate dehydrogenase (SDH activity, capillarization, myonuclear density, myoglobin (Mb concentration and Mb mRNA expression of high and low oxidative muscle fibres. After 3 weeks of CCH, CSA, SDH activity, Mb concentration, capillary and myonuclear density of both muscle fibre types were similar as under normoxia. In contrast, staining intensity for Mb mRNA of hypoxic high oxidative muscle fibres was 94% higher than that of normoxic controls (P<0.001. Between 3 and 6 weeks of CCH, CSA of high and low oxidative muscle fibres increased by 25 and 30%, respectively. This was similar to normoxic controls. Capillary and myonuclear density were not changed by CCH. However, in high oxidative muscle fibres of fish maintained under CCH, SDH activity, Mb concentration as well as Mb mRNA content were higher by 86%, 138% and 90%, respectively, than in muscle fibres of fish kept under normoxia (P<0.001. In low oxidative muscle fibres, SDH activity, Mb and Mb mRNA content were not significantly changed. Under normoxia, the calculated interstitial oxygen tension required to prevent anoxic cores in muscle fibres (PO2crit of high oxidative muscle fibres was between 1.0 and 1.7 mmHg. These values were similar at 3 and 6 weeks CCH. We conclude that high oxidative skeletal muscle fibres of zebrafish continue to grow and increase oxidative capacity during CCH. Oxygen supply to mitochondria in these fibres may be facilitated by an increased Mb concentration, which is regulated by an increase in Mb mRNA content per myonucleus.

Human erythropoietin response to hypocapnic hypoxia, normocapnic hypoxia, and hypocapnic normoxia

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Klausen, T; Christensen, H; Hansen, J M

1996-01-01

This study investigated the human erythropoietin (EPO) response to short-term hypocapnic hypoxia, its relationship to a normoxic or hypoxic increase of the haemoglobin oxygen affinity, and its suppression by the addition of CO2 to the hypoxic gas. On separate days, eight healthy male subjects were...

Effects of Acute Hypoxia and Reoxygenation on Physiological and Immune Responses and Redox Balance of Wuchang Bream (Megalobrama amblycephala Yih, 1955

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Nan Chen

2017-06-01

Full Text Available To study Megalobrama amblycephala adaption to water hypoxia, the changes in physiological levels, innate immune responses, redox balance of M.amblycephala during hypoxia were investigated in the present study. When M. amblycephala were exposed to different dissolved oxygen (DO including control (DO: 5.5 mg/L and acute hypoxia (DO: 3.5 and 1.0 mg/L, respectively, hemoglobin (Hb, methemoglobin (MetHb, glucose, Na+, succinatedehydrogenase (SDH, lactate, interferon alpha (IFNα, and lysozyme (LYZ, except hepatic glycogen and albumin gradually increased with the decrease of DO level. When M. amblycephala were exposed to different hypoxia time including 0.5 and 6 h (DO: 3.5 mg/L, and then reoxygenation for 24 h after 6 h hypoxia, Hb, MetHb, glucose, lactate, and IFNα, except Na+, SDH, hepatic glycogen, albumin, and LYZ increased with the extension of hypoxia time, while the above investigated indexes (except albumin, IFNα, and LYZ decreased after reoxygenation. On the other hand, the liver SOD, CAT, hydrogen peroxide (H2O2, and total ROS were all remained at lower levels under hypoxia stress. Finally, Hif-1α protein in the liver, spleen, and gill were increased with the decrease of oxygen concentration and prolongation of hypoxia time. Interestingly, one Hsp70 isoforms mediated by internal ribozyme entry site (IRES named junior Hsp70 was only detected in liver, spleen and gill. Taken together, these results suggest that hypoxia affects M. amblycephala physiology and reduces liver oxidative stress. Hypoxia-reoxygenation stimulates M. amblycephala immune parameter expressions, while Hsp70 response to hypoxia is tissue-specific.

Seasonal and interannual effects of hypoxia on fish habitat quality in central Lake Erie

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Arend, Kristin K.; Beletsky, Dmitry; DePinto, Joseph; Ludsin, Stuart A.; Roberts, James J.; Rucinski, Daniel K.; Scavia, Donald; Schwab, David J.; Höök, Tomas O.

2011-01-01

1. Hypoxia occurs seasonally in many stratified coastal marine and freshwater ecosystems when bottom dissolved oxygen (DO) concentrations are depleted below 2–3 mg O2 L-1. 2. We evaluated the effects of hypoxia on fish habitat quality in the central basin of Lake Erie from 1987 to 2005, using bioenergetic growth rate potential (GRP) as a proxy for habitat quality. We compared the effect of hypoxia on habitat quality of (i) rainbow smelt, Osmerus mordax mordax Mitchill (young-of-year, YOY, and adult), a cold-water planktivore, (ii) emerald shiner, Notropis atherinoides Rafinesque (adult), a warm-water planktivore, (iii) yellow perch, Perca flavescens Mitchill (YOY and adult), a cool-water benthopelagic omnivore and (iv) round goby Neogobius melanostomus Pallas (adult) a eurythermal benthivore. Annual thermal and DO profiles were generated from 1D thermal and DO hydrodynamics models developed for Lake Erie’s central basin. 3. Hypoxia occurred annually, typically from mid-July to mid-October, which spatially and temporally overlaps with otherwise high benthic habitat quality. Hypoxia reduced the habitat quality across fish species and life stages, but the magnitude of the reduction varied both among and within species because of the differences in tolerance to low DO levels and warm-water temperatures. 4. Across years, trends in habitat quality mirrored trends in phosphorus concentration and water column oxygen demand in central Lake Erie. The per cent reduction in habitat quality owing to hypoxia was greatest for adult rainbow smelt and round goby (mean: -35%), followed by adult emerald shiner (mean: -12%), YOY rainbow smelt (mean: -10%) and YOY and adult yellow perch (mean: -8.5%). 5. Our results highlight the importance of differential spatiotemporally interactive effects of DO and temperature on relative fish habitat quality and quantity. These effects have the potential to influence the performance of individual fish species as well as population dynamics

Hypoxia, HIF-1 Regulation and Cancer Therapy

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Groot, A.J.

2008-01-01

Oxygen insufficiency (hypoxia) is a common feature of human cancer and associated with tumor aggressiveness and poor clinical outcome. Furthermore, hypoxic tumors are more resistant to ionizing radiation and chemotherapy contributing to their unfavorable prognosis. The oxygen sensing pathway is

Seasonal hypoxia in eutrophic stratified coastal shelves: mechanisms, sensibilities and interannual variability from the North-Western Black Sea case

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Capet, A.; Beckers, J.-M.; Grégoire, M.

2012-12-01

The Black Sea north-western shelf (NWS) is a~shallow eutrophic area in which seasonal stratification of the water column isolates bottom waters from the atmosphere and prevents ventilation to compensate for the large consumption of oxygen, due to respiration in the bottom waters and in the sediments. A 3-D coupled physical biogeochemical model is used to investigate the dynamics of bottom hypoxia in the Black Sea NWS at different temporal scales from seasonal to interannual (1981-2009) and to differentiate the driving factors (climatic versus eutrophication) of hypoxic conditions in bottom waters. Model skills are evaluated by comparison with 14 500 in-situ oxygen measurements available in the NOAA World Ocean Database and the Black Sea Commission data. The choice of skill metrics and data subselections orientate the validation procedure towards specific aspects of the oxygen dynamics, and prove the model's ability to resolve the seasonal cycle and interannual variability of oxygen concentration as well as the spatial location of the oxygen depleted waters and the specific threshold of hypoxia. During the period 1981-2009, each year exhibits seasonal bottom hypoxia at the end of summer. This phenomenon essentially covers the northern part of the NWS, receiving large inputs of nutrients from the Danube, Dniestr and Dniepr rivers, and extends, during the years of severe hypoxia, towards the Romanian Bay of Constanta. In order to explain the interannual variability of bottom hypoxia and to disentangle its drivers, a statistical model (multiple linear regression) is proposed using the long time series of model results as input variables. This statistical model gives a general relationship that links the intensity of hypoxia to eutrophication and climate related variables. The use of four predictors allows to reproduce 78% of hypoxia interannual variability: the annual nitrate discharge (N), the sea surface temperature in the month preceding stratification (T), the

Assessing and addressing the re-eutrophication of Lake Erie: central basin hypoxia

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Scavia, Donald; Allan, J. David; Arend, Kristin K.; Bartell, Steven; Beletsky, Dmitry; Bosch, Nate S.; Brandt, Stephen B.; Briland, Ruth D.; Daloğlu, Irem; DePinto, Joseph V.; Dolan, David M.; Evans, Mary Anne; Farmer, Troy M.; Goto, Daisuke; Han, Haejin; Höök, Tomas O.; Knight, Roger; Ludsin, Stuart A.; Mason, Doran; Michalak, Anna M.; Richards, R. Peter; Roberts, James J.; Rucinski, Daniel K.; Rutherford, Edward; Schwab, David J.; Sesterhenn, Timothy M.; Zhang, Hongyan; Zhou, Yuntao

2014-01-01

Relieving phosphorus loading is a key management tool for controlling Lake Erie eutrophication. During the 1960s and 1970s, increased phosphorus inputs degraded water quality and reduced central basin hypolimnetic oxygen levels which, in turn, eliminated thermal habitat vital to cold-water organisms and contributed to the extirpation of important benthic macroinvertebrate prey species for fishes. In response to load reductions initiated in 1972, Lake Erie responded quickly with reduced water-column phosphorus concentrations, phytoplankton biomass, and bottom-water hypoxia (dissolved oxygen 2) requires cutting total phosphorus loads by 46% from the 2003–2011 average or reducing dissolved reactive phosphorus loads by 78% from the 2005–2011 average. Reductions to these levels are also protective of fish habitat. We provide potential approaches for achieving those new loading targets, and suggest that recent load reduction recommendations focused on western basin cyanobacteria blooms may not be sufficient to reduce central basin hypoxia to 2000 km2.

Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

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Bethany L Peterson

Full Text Available Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6 and older (postnatal day 20 age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

Blunted neuronal calcium response to hypoxia in naked mole-rat hippocampus.

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Peterson, Bethany L; Larson, John; Buffenstein, Rochelle; Park, Thomas J; Fall, Christopher P

2012-01-01

Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.

Reversal of Increasing Tropical Ocean Hypoxia Trends With Sustained Climate Warming

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Fu, Weiwei; Primeau, Francois; Keith Moore, J.; Lindsay, Keith; Randerson, James T.

2018-04-01

Dissolved oxygen (O2) is essential for the survival of marine animals. Climate change impacts on future oxygen distributions could modify species biogeography, trophic interactions, biodiversity, and biogeochemistry. The Coupled Model Intercomparison Project Phase 5 models predict a decreasing trend in marine O2 over the 21st century. Here we show that this increasing hypoxia trend reverses in the tropics after 2100 in the Community Earth System Model forced by atmospheric CO2 from the Representative Concentration Pathway 8.5 and Extended Concentration Pathway 8.5. In tropical intermediate waters between 200 and 1,000 m, the model predicts a steady decline of O2 and an expansion of oxygen minimum zones (OMZs) during the 21st century. By 2150, however, the trend reverses with oxygen concentration increasing and OMZ volume shrinking through 2300. A novel five-box model approach in conjunction with output from the full Earth system model is used to separate the contributions of biological and physical processes to the trends in tropical oxygen. The tropical O2 recovery is caused mainly by reductions in tropical biological export, coupled with a modest increase in ventilation after 2200. The time-evolving oxygen distribution impacts marine nitrogen cycling, with potentially important climate feedbacks.

Medical Oxygen Concentrator for Microgravity Operation, Phase I

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National Aeronautics and Space Administration — We have all seen people carrying portable oxygen tanks or concentrators to provide critical life support respiratory oxygen. Heavy, bulky, and for O2 concentrators,...

Comparative evaluation of diffusion hypoxia and psychomotor skills with or without postsedation oxygenation following administration of nitrous oxide in children undergoing dental procedures: A clinical study

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Vineet Inder Singh Khinda

2016-01-01

Full Text Available Background: Diffusion hypoxia is the most serious potential complication associated with nitrous oxide. It occurs during the recovery period. Hence, administration of 100% oxygen is mandatory as suggested by many authors. Aim: The aim of this study is to evaluate the occurrence/nonoccurrence of diffusion hypoxia in two groups of patients undergoing routine dental treatment under nitrous oxide sedation when one group is subjected to 7 min of postsedation oxygenation and the second group of the patients is made to breathe room air for the similar period. Materials and Methods: A total of sixty patients within the age group of 7–10 years requiring invasive dental procedures were randomly divided into two groups of 30 each using chit method. In the control group, patients were administered 100% oxygen postsedation, whereas, in the study group, patients were made to breathe room air postsedation. Various parameters (pulse rate, respiratory rate, blood pressure, and oxygen saturation [SpO2] were recorded pre- and post-operatively. Data were collected and then sent for statistical analysis. Results: The mean postoperative SpO2 at measurement times 1, 3, 5, and 7 min in both the groups was higher than the mean preoperative SpO2. This increase was statistically significant. No significant difference was found between the Trieger test scores. Conclusion: This study proves that clinical occurrence of diffusion hypoxia is not possible while following the routine procedure of nitrous oxide sedation.

Hypoxia by degrees: Establishing definitions for a changing ocean

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Hofmann, A. F.; Peltzer, E. T.; Walz, P. M.; Brewer, P. G.

2011-12-01

The marked increase in occurrences of low oxygen events on continental shelves coupled with observed expansion of low oxygen regions of the ocean has drawn significant scientific and public attention. With this has come the need for the establishment of better definitions for widely used terms such as "hypoxia" and "dead zones". Ocean chemists and physicists use concentration units such as μmolO2/kg for reporting since these units are independent of temperature, salinity and pressure and are required for mass balances and for numerical models of ocean transport. Much of the reporting of dead zone occurrences is in volumetric concentration units of mlO 2/l or mgO 2/l for historical reasons. And direct measurements of the physiological state of marine animals require reporting of the partial pressure of oxygen (pO 2) in matm or kPa since this provides the thermodynamic driving force for molecular transfer through tissue. This necessarily incorporates temperature and salinity terms and thus accommodates changes driven by climate warming and the influence of the very large temperature range around the world where oxygen limiting values are reported. Here we examine the various definitions used and boundaries set and place them within a common framework. We examine the large scale ocean pO 2 fields required for pairing with pCO 2 data for examination of the combined impacts of ocean acidification and global warming. The term "dead zones", which recently has received considerable attention in both the scientific literature and the press, usually describes shallow, coastal regions of low oxygen caused either by coastal eutrophication and organic matter decomposition or by upwelling of low oxygen waters. While we make clear that bathyal low oxygen waters should not be confused with shallow-water "dead zones", as deep water species are well adapted, we show that those waters represent a global vast reservoir of low oxygen water which can readily be entrained in upwelling

Salicylic acid induces apoptosis in colon carcinoma cells grown in-vitro: Influence of oxygen and salicylic acid concentration

Energy Technology Data Exchange (ETDEWEB)

Zitta, Karina; Meybohm, Patrick; Bein, Berthold; Huang, Ying; Heinrich, Christin; Scholz, Jens; Steinfath, Markus; Albrecht, Martin, E-mail: Albrecht@anaesthesie.uni-kiel.de

2012-04-15

In solid tumors the hypoxic environment can promote tumor progression and resistance to therapy. Recently, acetylsalicylic acid a major component of analgesic drugs and its metabolite salicylic acid (SA) have been shown to reduce the risk of colon cancer, but the mechanisms of action remain still unclear. Here we elucidate the effects of physiologically relevant concentrations of SA on colon carcinoma cells (CaCo-2) grown under normoxic and hypoxic conditions. Western blotting, caspase-3/7 apoptosis assays, MTS cell-proliferation assays, LDH cytotoxicity assays and hydrogen peroxide measurements were performed to investigate the effects of 1 and 10 {mu}M SA on CaCo-2 cells grown under normoxic conditions and cells exposed to hypoxia. Under normoxic conditions, SA did not influence cell proliferation or LDH release of CaCo-2 cells. However, caspase-3/7 activity was significantly increased. Under hypoxia, cell proliferation was reduced and LDH release and caspase-3/7 activities were increased. None of these parameters was altered by the addition of SA under hypoxic conditions. Hypoxia increased hydrogen peroxide concentrations 300-fold and SA significantly augmented the release of hydrogen peroxide under normoxic, but not under hypoxic conditions. Phosphorylation of the pro-survival kinases akt and erk1/2 was not changed by SA under hypoxic conditions, whereas under normoxia SA reduced phosphorylation of erk1/2 after 2 hours. We conclude that in colon carcinoma cells effects of SA on apoptosis and cellular signaling are dependent on the availability of oxygen. -- Highlights: Black-Right-Pointing-Pointer Effects of salicylic acid on colon carcinoma cells grown under normoxic and hypoxic conditions Black-Right-Pointing-Pointer Salicylic acid increases caspase-3/7 activity and hydrogen peroxide release under normoxia Black-Right-Pointing-Pointer Salicylic acid decreases pro-survival erk-1/2 phosphorylation under normoxia Black-Right-Pointing-Pointer Salicylic acid does

Extreme hypoxia tolerance of naked mole-rat brain.

Science.gov (United States)

Larson, John; Park, Thomas J

2009-12-09

Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

Deriving mechanisms responsible for the lack of correlation between hypoxia and acidity in solid tumors.

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Hamid R Molavian

Full Text Available Hypoxia and acidity are two main microenvironmental factors intimately associated with solid tumors and play critical roles in tumor growth and metastasis. The experimental results of Helmlinger and colleagues (Nature Medicine 3, 177, 1997 provide evidence of a lack of correlation between these factors on the micrometer scale in vivo and further show that the distribution of pH and pO(2 are heterogeneous. Here, using computational simulations, grounded in these experimental results, we show that the lack of correlation between pH and pO(2 and the heterogeneity in their shapes are related to the heterogeneous concentration of buffers and oxygen in the blood vessels, further amplified by the network of blood vessels and the cell metabolism. We also demonstrate that, although the judicious administration of anti-angiogenesis agents (normalization process in tumors may lead to recovery of the correlation between hypoxia and acidity, it may not normalize the pH throughout the whole tumor. However, an increase in the buffering capacity inside the blood vessels does appear to increase the extracellular pH throughout the whole tumor. Based on these results, we propose that the application of anti-angiogenic agents and at the same time increasing the buffering capacity of the tumor extracellular environment may be the most efficient way of normalizing the tumor microenvironment. As a by-product of our simulation we show that the recently observed lack of correlation between glucose consumption and hypoxia in cells which rely on respiration is related to the inhomogeneous consumption of glucose to oxygen concentration. We also demonstrate that this lack of correlation in cells which rely on glycolysis could be related to the heterogeneous concentration of oxygen inside the blood vessels.

Preliminary Study of Oxygen-Enhanced Longitudinal Relaxation in MRI: A Potential Novel Biomarker of Oxygenation Changes in Solid Tumors

International Nuclear Information System (INIS)

O'Connor, James P.B.; Naish, Josephine H.; Parker, Geoff J.M.; Waterton, John C.; Watson, Yvonne; Jayson, Gordon C.; Buonaccorsi, Giovanni A.; Cheung, Sue; Buckley, David L.; McGrath, Deirdre M.; West, Catharine M.L.; Davidson, Susan E.; Roberts, Caleb; Mills, Samantha J.; Mitchell, Claire L.; Hope, Lynn; Ton, N. Chan; Jackson, Alan

2009-01-01

Purpose: There is considerable interest in developing non-invasive methods of mapping tumor hypoxia. Changes in tissue oxygen concentration produce proportional changes in the magnetic resonance imaging (MRI) longitudinal relaxation rate (R 1 ). This technique has been used previously to evaluate oxygen delivery to healthy tissues and is distinct from blood oxygenation level-dependent (BOLD) imaging. Here we report application of this method to detect alteration in tumor oxygenation status. Methods and materials: Ten patients with advanced cancer of the abdomen and pelvis underwent serial measurement of tumor R 1 while breathing medical air (21% oxygen) followed by 100% oxygen (oxygen-enhanced MRI). Gadolinium-based dynamic contrast-enhanced MRI was then performed to compare the spatial distribution of perfusion with that of oxygen-induced ΔR 1 . Results: ΔR 1 showed significant increases of 0.021 to 0.058 s -1 in eight patients with either locally recurrent tumor from cervical and hepatocellular carcinomas or metastases from ovarian and colorectal carcinomas. In general, there was congruency between perfusion and oxygen concentration. However, regional mismatch was observed in some tumor cores. Here, moderate gadolinium uptake (consistent with moderate perfusion) was associated with low area under the ΔR 1 curve (consistent with minimal increase in oxygen concentration). Conclusions: These results provide evidence that oxygen-enhanced longitudinal relaxation can monitor changes in tumor oxygen concentration. The technique shows promise in identifying hypoxic regions within tumors and may enable spatial mapping of change in tumor oxygen concentration.

Toward a quantitative reconstruction of hypoxia from varve records in the large perialpin Lake Bourget over the last 150 years

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Jenny, J.-P.; Arnaud, F.; Dorioz, J. M.; Giguet Covex, C.; Frossard, V.; Sabatier, P.; Millet, L.; Reyss, J. L.; Tachikawa, K.; Romeyer, O.; Pignol, C.; Mallet, E.; Perga, M. E.

2012-04-01

Hypoxia -defined as dissolved oxygen ≤2 mg/l- is a severe detrimental factor for aquatic environments. In lakes, despit the importance for management, it is generally still hard to estimate hypoxia because of the lack of appropriate proxies or restricted number of sample cores. In this study, by using (40) sediment core data from chosen depths, we propose to go a step further toward a quantitative reconstruction of hypoxia integrating the extension of hypoxic water layer, both through space (volume) and time (yearly value). For that we went a step further in using an existing proxy: varve preservation. It is generally well-adapted for hypoxia detection, but not yet developed for small scale time and space variations through a complete large lake basin. Varves preservation is the consequence of the death of most of benthic macro-organisms that normally mix-up first millimetres of sediments, due to oxygen depletion. In Lake Bourget recent laminated sediments correspond to biochemical varves. We assume that their preservation results from a threshold in dissolved oxygen concentrations induced by seasonal hypoxia. Chironomids, organic matter and Mn/Fe ratio (XRF) were used as complementary proxies of hypoxia to validate our assumptions concerning varves. Our results show that volume of hypoxia can be annually estimated according to varve records through lake. Volumes of hypoxia varied through time in the Lake Bourget. Sediments recorded first the onset of severe hypoxia in the deepest part of the basin (-140m) in AD 1935±1, corresponding to 11.103m3 of hypoxic waters. Then hypoxic surface progressively extended on the slope until reaching a maximum at -90m in AD 1960, leading to 306.103m3 of hypoxic waters. After a retreat dated to AD 1980, hypoxia seemed to re-extend until today. Those fluctuations over the "oscillating zone" of hypoxia (-90 to -133m) were compared with potential forcing factors. The onset of hypolimnetic hypoxia is commonly attributed to

Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate.

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Yin, Chengqian; He, Dan; Chen, Shuyang; Tan, Xiaoling; Sang, Nianli

2016-07-26

Molecular oxygen is the final electron acceptor in cellular metabolism but cancer cells often become adaptive to hypoxia, which promotes resistance to chemotherapy and radiation. The reduction of endogenous glycolytic pyruvate to lactate is known as an adaptive strategy for hypoxic cells. Whether exogenous pyruvate is required for hypoxic cell proliferation by either serving as an electron acceptor or a biosynthetic substrate remains unclear. By using both hypoxic and ρ0 cells defective in electron transfer chain, we show that exogenous pyruvate is required to sustain proliferation of both cancer and non-cancer cells that cannot utilize oxygen. Particularly, we show that absence of pyruvate led to glycolysis inhibition and AMPK activation along with decreased NAD+ levels in ρ0 cells; and exogenous pyruvate increases lactate yield, elevates NAD+/NADH ratio and suppresses AMPK activation. Knockdown of lactate dehydrogenase significantly inhibits the rescuing effects of exogenous pyruvate. In contrast, none of pyruvate-derived metabolites tested (including acetyl-CoA, α-ketoglutarate, succinate and alanine) can replace pyruvate in supporting ρ0 cell proliferation. Knockdown of pyruvate carboxylase, pyruvate dehydrogenase and citrate synthase do not impair exogenous pyruvate to rescue ρ0 cells. Importantly, we show that exogenous pyruvate relieves ATP insufficiency and mTOR inhibition and promotes proliferation of hypoxic cells, and that well-oxygenated cells release pyruvate, providing a potential in vivo source of pyruvate. Taken together, our data support a novel pyruvate cycle model in which oxygenated cells release pyruvate for hypoxic cells as an oxygen surrogate. The pyruvate cycle may be targeted as a new therapy of hypoxic cancers.

The role of hypoxia in structuring macrobenthos community off the Louisiana shelf

Science.gov (United States)

Shivarudrappa, S. K.; Briggs, K.

2013-12-01

Core samples were collected from 24 box cores belonging to four different provinces with varying hypoxia frequency and history in the northern Gulf of Mexico. Macrobenthos from these four provinces were sampled in spring, summer and late-summer seasons. According to historical data of bottom water oxygen concentration since 1985, the control province was exposed to hypoxia rarefaction curves of expected species diversity. Impact of grain size and organic matter concentration on the community structure was assessed using non-metric multi-dimensional scaling. Different species dominated by their abundance or their biomass at all four provinces, but the effect was magnified in the provinces other than the control. Capitellid, cossurid and spionid polychaetes dominated by abundance, whereas maldanid and nephtyid polychaetes and Nemerteans dominated by biomass. This implies that the fauna responsible for dominance by their abundance were small, opportunistic deposit feeders, and that large carnivores contributed to dominance by their biomass. Although species and abundance changed from province to province and season to season, the functional groups were nevertheless dominated, in order, by subsurface deposit feeders, surface deposit feeders, and carnivores at all provinces in all three seasons. This study provides insight into compositional changes in the macrobenthic community due to hypoxia and subsequent recovery from hypoxia on the northern Gulf of Mexico shelf between the Mississippi and Atchafalaya Rivers.

Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia

Science.gov (United States)

Carreau, Aude; Hafny-Rahbi, Bouchra El; Matejuk, Agata; Grillon, Catherine; Kieda, Claudine

2011-01-01

Abstract Oxygen supply and diffusion into tissues are necessary for survival. The oxygen partial pressure (pO2), which is a key component of the physiological state of an organ, results from the balance between oxygen delivery and its consumption. In mammals, oxygen is transported by red blood cells circulating in a well-organized vasculature. Oxygen delivery is dependent on the metabolic requirements and functional status of each organ. Consequently, in a physiological condition, organ and tissue are characterized by their own unique ‘tissue normoxia’ or ‘physioxia’ status. Tissue oxygenation is severely disturbed during pathological conditions such as cancer, diabetes, coronary heart disease, stroke, etc., which are associated with decrease in pO2, i.e. ‘hypoxia’. In this review, we present an array of methods currently used for assessing tissue oxygenation. We show that hypoxia is marked during tumour development and has strong consequences for oxygenation and its influence upon chemotherapy efficiency. Then we compare this to physiological pO2 values of human organs. Finally we evaluate consequences of physioxia on cell activity and its molecular modulations. More importantly we emphasize the discrepancy between in vivo and in vitro tissue and cells oxygen status which can have detrimental effects on experimental outcome. It appears that the values corresponding to the physioxia are ranging between 11% and 1% O2 whereas current in vitro experimentations are usually performed in 19.95% O2, an artificial context as far as oxygen balance is concerned. It is important to realize that most of the experiments performed in so-called normoxia might be dangerously misleading. PMID:21251211

Protein S-glutathionylation induced by hypoxia increases hypoxia-inducible factor-1α in human colon cancer cells.

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Jeon, Daun; Park, Heon Joo; Kim, Hong Seok

2018-01-01

Hypoxia is a common characteristic of many types of solid tumors. Intratumoral hypoxia selects for tumor cells that survive in a low oxygen environment, undergo epithelial-mesenchymal transition, are more motile and invasive, and show gene expression changes driven by hypoxia-inducible factor-1α (HIF-1α) activation. Therefore, targeting HIF-1α is an attractive strategy for disrupting multiple pathways crucial for tumor growth. In the present study, we demonstrated that hypoxia increases the S-glutathionylation of HIF-1α and its protein levels in colon cancer cells. This effect is significantly prevented by decreasing oxidized glutathione as well as glutathione depletion, indicating that S-glutathionylation and the formation of protein-glutathione mixed disulfides is related to HIF-1α protein levels. Moreover, colon cancer cells expressing glutaredoxin 1 are resistant to inducing HIF-1α and expressing hypoxia-responsive genes under hypoxic conditions. Therefore, S-glutathionylation of HIF-1α induced by tumor hypoxia may be a novel therapeutic target for the development of new drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxygen, the lead actor in the pathophysiologic drama: enactment of the trinity of normoxia, hypoxia, and hyperoxia in disease and therapy.

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Kulkarni, Aditi C; Kuppusamy, Periannan; Parinandi, Narasimham

2007-10-01

Aerobic life has evolved a dependence on molecular oxygen for its mere survival. Mitochondrial oxidative phosphorylation absolutely requires oxygen to generate the currency of energy in aerobes. The physiologic homeostasis of these organisms is strictly maintained by optimal cellular and tissue-oxygenation status through complex oxygen-sensing mechanisms, signaling cascades, and transport processes. In the event of fluctuating oxygen levels leading to either an increase (hyperoxia) or decrease (hypoxia) in cellular oxygen, the organism faces a crisis involving depletion of energy reserves, altered cell-signaling cascades, oxidative reactions/events, and cell death or tissue damage. Molecular oxygen is activated by both nonenzymatic and enzymatic mechanisms into highly reactive oxygen species (ROS). Aerobes have evolved effective antioxidant defenses to counteract the reactivity of ROS. Although the ROS are also required for many normal physiologic functions of the aerobes, overwhelming production of ROS coupled with their insufficient scavenging by endogenous antioxidants will lead to detrimental oxidative stress. Needless to say, molecular oxygen is at the center of oxygenation, oxidative phosphorylation, and oxidative stress. This review focuses on the biology and pathophysiology of oxygen, with an emphasis on transport, sensing, and activation of oxygen, oxidative phosphorylation, oxygenation, oxidative stress, and oxygen therapy.

Is hypoxia training good for muscles and exercise performance?

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Vogt, Michael; Hoppeler, Hans

2010-01-01

Altitude training has become very popular among athletes as a means to further increase exercise performance at sea level or to acclimatize to competition at altitude. Several approaches have evolved during the last few decades, with "live high-train low" and "live low-train high" being the most popular. This review focuses on functional, muscular, and practical aspects derived from extensive research on the "live low-train high" approach. According to this, subjects train in hypoxia but remain under normoxia for the rest of the time. It has been reasoned that exercising in hypoxia could increase the training stimulus. Hypoxia training studies published in the past have varied considerably in altitude (2300-5700 m) and training duration (10 days to 8 weeks) and the fitness of the subjects. The evidence from muscle structural, biochemical, and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available performance capacity data such as maximal oxygen uptake (Vo(2)max) and (maximal) power output, hypoxia as a supplement to training is not consistently found to be advantageous for performance at sea level. Stronger evidence exists for benefits of hypoxic training on performance at altitude. "Live low-train high" may thus be considered when altitude acclimatization is not an option. In addition, the complex pattern of gene expression adaptations induced by supplemental training in hypoxia, but not normoxia, suggest that muscle tissue specifically responds to hypoxia. Whether and to what degree these gene expression changes translate into significant changes in protein concentrations that are ultimately responsible for observable structural or functional phenotypes remains open. It is conceivable that the global functional markers such as Vo(2)max and (maximal) power output are too coarse to detect more subtle changes that might still be functionally relevant, at least to high-level athletes.

Oxygen concentrators performance with nitrous oxide at 50:50 volume

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Jorge Ronaldo Moll

2014-06-01

Full Text Available Background and objectives: Few investigations have addressed the safety of oxygen from concentrators for use in anesthesia in association with nitrous oxide. This study evaluated the percent of oxygen from a concentrator in association with nitrous oxide in a semi-closed rebreathing circuit. Methods: Adult patients undergoing low risk surgery were randomly allocated into two groups, receiving a fresh gas flow of oxygen from concentrators (O293 or of oxygen from concentrators and nitrous oxide (O293N2O. The fraction of inspired oxygen and the percentage of oxygen from fresh gas flow were measured every 10 min. The ratio of FiO2/oxygen concentration delivered was compared at various time intervals and between the groups. Results: Thirty patients were studied in each group. There was no difference in oxygen from concentrators over time for both groups, but there was a significant improvement in the FiO2 (p < 0.001 for O293 group while a significant decline (p < 0.001 for O293N2O. The FiO2/oxygen ratio varied in both groups, reaching a plateau in the O293 group. Pulse oximetry did not fall below 98.5% in either group. Conclusion: The FiO2 in the mixture of O293 and nitrous oxide fell during the observation period although oxygen saturation was higher than 98.5% throughout the study. Concentrators can be considered a stable source of oxygen for use during short anesthetic procedures, either pure or in association with nitrous oxide at 50:50 volume.

Dynamics and distribution of natural and human-caused hypoxia

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Rabalais, N. N.; Díaz, R. J.; Levin, L. A.; Turner, R. E.; Gilbert, D.; Zhang, J.

2010-02-01

Water masses can become undersaturated with oxygen when natural processes alone or in combination with anthropogenic processes produce enough organic carbon that is aerobically decomposed faster than the rate of oxygen re-aeration. The dominant natural processes usually involved are photosynthetic carbon production and microbial respiration. The re-supply rate is indirectly related to its isolation from the surface layer. Hypoxic water masses (hypoxic areas has been exacerbated by any combination of interactions that increase primary production and accumulation of organic carbon leading to increased respiratory demand for oxygen below a seasonal or permanent pycnocline. Nutrient loading is likely to increase further as population growth and resource intensification rises, especially with increased dependency on crops using fertilizers, burning of fossil fuels, urbanization, and waste water generation. It is likely that the occurrence and persistence of hypoxia will be even more widespread and have more impacts than presently observed. Global climate change will further complicate the causative factors in both natural and human-caused hypoxia. The likelihood of strengthened stratification alone, from increased surface water temperature as the global climate warms, is sufficient to worsen hypoxia where it currently exists and facilitate its formation in additional waters. Increased precipitation that increases freshwater discharge and flux of nutrients will result in increased primary production in the receiving waters up to a point. The interplay of increased nutrients and stratification where they occur will aggravate and accelerate hypoxia. Changes in wind fields may expand oxygen minimum zones onto more continental shelf areas. On the other hand, not all regions will experience increased precipitation, some oceanic water temperatures may decrease as currents shift, and frequency and severity of tropical storms may increase and temporarily disrupt hypoxia more

Redox signaling during hypoxia in mammalian cells

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Kimberly A. Smith

2017-10-01

Full Text Available Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS such as hydrogen peroxide (H2O2 occurs through the reversible oxidation of cysteine thiol groups, resulting in structural modifications that can change protein function profoundly. Mitochondria are an important source of ROS generation, and studies reveal that superoxide generation by the electron transport chain increases during hypoxia. Other sources of ROS, such as the NAD(PH oxidases, may also generate oxidant signals in hypoxia. This review considers the growing body of work indicating that increased ROS signals during hypoxia are responsible for regulating the activation of protective mechanisms in diverse cell types.

Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise

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Rostika Flora

2012-08-01

Full Text Available Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α. The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise.Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium.Results: Both, HIF-1α protein and VEGF were increased (p < 0.05 in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66. Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35, while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73. The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59 in the aerobic group and strong in the anaerobic group (r = 0.69.Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise. (Med J Indones. 2012;21:133-40Keywords: Exercise, HIF-1α, myocardium, VEGF

Reactive oxygen species-driven HIF1α triggers accelerated glycolysis in endothelial cells exposed to low oxygen tension

International Nuclear Information System (INIS)

Paik, Jin-Young; Jung, Kyung-Ho; Lee, Jin-Hee; Park, Jin-Won; Lee, Kyung-Han

2017-01-01

Endothelial cells and their metabolic state regulate glucose transport into underlying tissues. Here, we show that low oxygen tension stimulates human umbilical vein endothelial cell 18 F–fluorodeoxyglucose ( 18 F–FDG) uptake and lactate production. This was accompanied by augmented hexokinase activity and membrane Glut-1, and increased accumulation of hypoxia-inducible factor-1α (HIF1α). Restoration of oxygen reversed the metabolic effect, but this was blocked by HIF1α stabilization. Hypoxia-stimulated 18 F–FDG uptake was completely abrogated by silencing of HIF1α expression or by a specific inhibitor. There was a rapid and marked increase of reactive oxygen species (ROS) by hypoxia, and ROS scavenging or NADPH oxidase inhibition completely abolished hypoxia-stimulated HIF1α and 18 F–FDG accumulation, placing ROS production upstream of HIF1α signaling. Hypoxia-stimulated HIF1α and 18 F–FDG accumulation was blocked by the protein kinase C (PKC) inhibitor, staurosporine. The phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin, blocked hypoxia-stimulated 18 F–FDG uptake and attenuated hypoxia-responsive element binding of HIF1α without influencing its accumulation. Thus, ROS-driven HIF1α accumulation, along with PKC and PI3K signaling, play a key role in triggering accelerated glycolysis in endothelial cells under hypoxia, thereby contributing to 18 F–FDG transport.

Single photon counting fluorescence lifetime detection of pericellular oxygen concentrations.

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Hosny, Neveen A; Lee, David A; Knight, Martin M

2012-01-01

Fluorescence lifetime imaging microscopy offers a non-invasive method for quantifying local oxygen concentrations. However, existing methods are either invasive, require custom-made systems, or show limited spatial resolution. Therefore, these methods are unsuitable for investigation of pericellular oxygen concentrations. This study describes an adaptation of commercially available equipment which has been optimized for quantitative extracellular oxygen detection with high lifetime accuracy and spatial resolution while avoiding systematic photon pile-up. The oxygen sensitive fluorescent dye, tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate [Ru(bipy)(3)](2+), was excited using a two-photon excitation laser. Lifetime was measured using a Becker & Hickl time-correlated single photon counting, which will be referred to as a TCSPC card. [Ru(bipy)(3)](2+) characterization studies quantified the influences of temperature, pH, cellular culture media and oxygen on the fluorescence lifetime measurements. This provided a precisely calibrated and accurate system for quantification of pericellular oxygen concentration based on measured lifetimes. Using this technique, quantification of oxygen concentrations around isolated viable chondrocytes, seeded in three-dimensional agarose gel, revealed a subpopulation of cells that exhibited significant spatial oxygen gradients such that oxygen concentration reduced with increasing proximity to the cell. This technique provides a powerful tool for quantifying spatial oxygen gradients within three-dimensional cellular models.

Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria.

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Bastos, Marcele F; Kayano, Ana Carolina A V; Silva-Filho, João Luiz; Dos-Santos, João Conrado K; Judice, Carla; Blanco, Yara C; Shryock, Nathaniel; Sercundes, Michelle K; Ortolan, Luana S; Francelin, Carolina; Leite, Juliana A; Oliveira, Rafaella; Elias, Rosa M; Câmara, Niels O S; Lopes, Stefanie C P; Albrecht, Letusa; Farias, Alessandro S; Vicente, Cristina P; Werneck, Claudio C; Giorgio, Selma; Verinaud, Liana; Epiphanio, Sabrina; Marinho, Claudio R F; Lalwani, Pritesh; Amino, Rogerio; Aliberti, Julio; Costa, Fabio T M

2018-03-20

Cerebral malaria (CM) is a multifactorial syndrome involving an exacerbated proinflammatory status, endothelial cell activation, coagulopathy, hypoxia, and accumulation of leukocytes and parasites in the brain microvasculature. Despite significant improvements in malaria control, 15% of mortality is still observed in CM cases, and 25% of survivors develop neurologic sequelae for life-even after appropriate antimalarial therapy. A treatment that ameliorates CM clinical signs, resulting in complete healing, is urgently needed. Previously, we showed a hyperbaric oxygen (HBO)-protective effect against experimental CM. Here, we provide molecular evidence that HBO targets brain endothelial cells by decreasing their activation and inhibits parasite and leukocyte accumulation, thus improving cerebral microcirculatory blood flow. HBO treatment increased the expression of aryl hydrocarbon receptor over hypoxia-inducible factor 1-α (HIF-1α), an oxygen-sensitive cytosolic receptor, along with decreased indoleamine 2,3-dioxygenase 1 expression and kynurenine levels. Moreover, ablation of HIF-1α expression in endothelial cells in mice conferred protection against CM and improved survival. We propose that HBO should be pursued as an adjunctive therapy in CM patients to prolong survival and diminish deleterious proinflammatory reaction. Furthermore, our data support the use of HBO in therapeutic strategies to improve outcomes of non-CM disorders affecting the brain.-Bastos, M. F., Kayano, A. C. A. V., Silva-Filho, J. L., Dos-Santos, J. C. K., Judice, C., Blanco, Y. C., Shryock, N., Sercundes, M. K., Ortolan, L. S., Francelin, C., Leite, J. A., Oliveira, R., Elias, R. M., Câmara, N. O. S., Lopes, S. C. P., Albrecht, L., Farias, A. S., Vicente, C. P., Werneck, C. C., Giorgio, S., Verinaud, L., Epiphanio, S., Marinho, C. R. F., Lalwani, P., Amino, R., Aliberti, J., Costa, F. T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen

Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia.

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Prabhakar, Nanduri R; Peng, Ying-Jie; Yuan, Guoxiang; Nanduri, Jayasri

2018-05-01

Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H 2 S production in the CB. Blockade of H 2 S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H 2 S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H 2 S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H 2 S. Inhibiting H 2 S synthesis prevented IH-evoked sympathetic activation and hypertension.

Impact of intermittent hypoxia and exercise on blood pressure and metabolic features from obese subjects suffering sleep apnea-hypopnea syndrome.

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González-Muniesa, P; Lopez-Pascual, A; de Andrés, J; Lasa, A; Portillo, M P; Arós, F; Durán, J; Egea, C J; Martinez, J A

2015-09-01

Strategies designed to reduce adiposity and cardiovascular-accompanying manifestations have been based on nutritional interventions conjointly with physical activity programs. The aim of this 13-week study was to investigate the putative benefits associated to hypoxia plus exercise on weight loss and relevant metabolic and cardiorespiratory variables, when prescribed to obese subjects with sleep apnea syndrome following dietary advice. The participants were randomly distributed in the following three groups: control, normoxia, and hypoxia. All the subjects received dietary advice while, additionally, normoxia group was trained under normal oxygen concentration and Hypoxia group under hypoxic conditions. There was a statistically significant decrease in fat-free mass (Kg) and water (%) on the control compared to normoxia group (p hypoxia compared to control group (p hypoxia group showed some specific benefits concerning appetite and cardiometabolic-related measurements as exertion time and diastolic blood pressure, with a therapeutical potential.

Characterization of hemodynamics and oxygenation in the renal cortex of rats

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Grosenick, Dirk; Wabnitz, Heidrun; Macdonald, Rainer; Niendorf, Thoralf; Cantow, Kathleen; Flemming, Bert; Arakelyan, Karen; Seeliger, Erdmann

2015-03-01

We have performed a pre-clinical study on 13 rats to investigate the potential of near-infrared spectroscopy for quantification of hemoglobin concentration and oxygen saturation of hemoglobin in the renal cortex of small animals. These measurements were combined with laser-Doppler fluxmetry and a fluorescence quenching technique for quantification of tissue oxygen tension. Hemoglobin concentration and oxygen saturation were determined from experimental data by a Monte Carlo model. The methods were applied to investigate and compare temporal changes during several types of interventions such as arterial and venous occlusions, as well as hyperoxia, hypoxia and hypercapnia induced by different mixtures of the inspired gas.

Dynamics and distribution of natural and human-caused hypoxia

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N. N. Rabalais

2010-02-01

Full Text Available Water masses can become undersaturated with oxygen when natural processes alone or in combination with anthropogenic processes produce enough organic carbon that is aerobically decomposed faster than the rate of oxygen re-aeration. The dominant natural processes usually involved are photosynthetic carbon production and microbial respiration. The re-supply rate is indirectly related to its isolation from the surface layer. Hypoxic water masses (<2 mg L⁻¹, or approximately 30% saturation can form, therefore, under "natural" conditions, and are more likely to occur in marine systems when the water residence time is extended, water exchange and ventilation are minimal, stratification occurs, and where carbon production and export to the bottom layer are relatively high. Hypoxia has occurred through geological time and naturally occurs in oxygen minimum zones, deep basins, eastern boundary upwelling systems, and fjords.

Hypoxia development and continuation in many areas of the world's coastal ocean is accelerated by human activities, especially where nutrient loading increased in the Anthropocene. This higher loading set in motion a cascading set of events related to eutrophication. The formation of hypoxic areas has been exacerbated by any combination of interactions that increase primary production and accumulation of organic carbon leading to increased respiratory demand for oxygen below a seasonal or permanent pycnocline. Nutrient loading is likely to increase further as population growth and resource intensification rises, especially with increased dependency on crops using fertilizers, burning of fossil fuels, urbanization, and waste water generation. It is likely that the occurrence and persistence of hypoxia will be even more widespread and have more impacts than presently observed.

Global climate change will further complicate the causative factors in both natural and human-caused hypoxia. The likelihood of

Combined effects of toxic cyanobacteria Microcystis aeruginosa and hypoxia on the physiological responses of triangle sail mussel Hyriopsis cumingii.

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Hu, Menghong; Wu, Fangli; Yuan, Mingzhe; Liu, Qigen; Wang, Youji

2016-04-05

The single and combined effects of toxic cyanobacteria Microcystis aeruginosa and hypoxia on the energy budget of triangle sail mussel Hyriopsis cumingii were determined in terms of scope for growth (SfG). Mussels were exposed to different combinations of toxic M. aeruginosa (0%, 50%, and 100% of total dietary dry weight) and dissolved oxygen concentrations (1, 3, and 6.0mg O2l(-1)) with a 3×3 factorial design for 14 days, followed by a recovery period with normal conditions for 7 days. Microcystin contents in mussel tissues increased with the increase in the exposed M. aeruginosa concentration at each sampling time. Adverse physiological responses of H. cumingii under toxic M. aeruginosa and hypoxic exposure were found in terms of clearance rate, absorption efficiency, respiration rate, excretion rate, and SfG. Results emphasized the importance of combined effects of hypoxia and toxic cyanobacteria on H. cumingii bioenergetic parameters, highlighted the interactive effects of toxic algae and hypoxia, and implied that the two stressors affected H. cumingii during the exposure period and showed carryover effects later. Thus, if H. cumingii is used as a bioremediation tool to eliminate M. aeruginosa, the waters should be oxygenated. Copyright © 2015 Elsevier B.V. All rights reserved.

Real-time determination of intracellular oxygen in bacteria using a genetically encoded FRET-based biosensor

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Potzkei Janko

2012-03-01

Full Text Available Abstract Background Molecular oxygen (O2 is one of the key metabolites of all obligate and facultative aerobic pro- and eukaryotes. It plays a fundamental role in energy homeostasis whereas oxygen deprivation, in turn, broadly affects various physiological and pathophysiological processes. Therefore, real-time monitoring of cellular oxygen levels is basically a prerequisite for the analysis of hypoxia-induced processes in living cells and tissues. Results We developed a genetically encoded Förster resonance energy transfer (FRET-based biosensor allowing the observation of changing molecular oxygen concentrations inside living cells. This biosensor named FluBO (fluorescent protein-based biosensor for oxygen consists of the yellow fluorescent protein (YFP that is sensitive towards oxygen depletion and the hypoxia-tolerant flavin-binding fluorescent protein (FbFP. Since O2 is essential for the formation of the YFP chromophore, efficient FRET from the FbFP donor domain to the YFP acceptor domain only occurs in the presence but not in the absence of oxygen. The oxygen biosensor was used for continuous real-time monitoring of temporal changes of O2 levels in the cytoplasm of Escherichia coli cells during batch cultivation. Conclusions FluBO represents a unique FRET-based oxygen biosensor which allows the non-invasive ratiometric readout of cellular oxygen. Thus, FluBO can serve as a novel and powerful probe for investigating the occurrence of hypoxia and its effects on a variety of (pathophysiological processes in living cells.

Developmental control of hypoxia during bud burst in grapevine.

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Meitha, Karlia; Agudelo-Romero, Patricia; Signorelli, Santiago; Gibbs, Daniel J; Considine, John A; Foyer, Christine H; Considine, Michael J

2018-05-01

Dormant or quiescent buds of woody perennials are often dense and in the case of grapevine (Vitis vinifera L.) have a low tissue oxygen status. The precise timing of the decision to resume growth is difficult to predict, but once committed, the increase in tissue oxygen status is rapid and developmentally regulated. Here, we show that more than a third of the grapevine homologues of widely conserved hypoxia-responsive genes and nearly a fifth of all grapevine genes possessing a plant hypoxia-responsive promoter element were differentially regulated during bud burst, in apparent harmony with resumption of meristem identity and cell-cycle gene regulation. We then investigated the molecular and biochemical properties of the grapevine ERF-VII homologues, which in other species are oxygen labile and function in transcriptional regulation of hypoxia-responsive genes. Each of the 3 VvERF-VIIs were substrates for oxygen-dependent proteolysis in vitro, as a function of the N-terminal cysteine. Collectively, these data support an important developmental function of oxygen-dependent signalling in determining the timing and effective coordination bud burst in grapevine. In addition, novel regulators, including GASA-, TCP-, MYB3R-, PLT-, and WUS-like transcription factors, were identified as hallmarks of the orderly and functional resumption of growth following quiescence in buds. © 2018 John Wiley & Sons Ltd.

Response of skeletal muscle mitochondria to hypoxia.

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Hoppeler, Hans; Vogt, Michael; Weibel, Ewald R; Flück, Martin

2003-01-01

This review explores the current concepts relating the structural and functional modifications of skeletal muscle mitochondria to the molecular mechanisms activated when organisms are exposed to a hypoxic environment. In contrast to earlier assumptions it is now established that permanent or long-term exposure to severe environmental hypoxia decreases the mitochondrial content of muscle fibres. Oxidative muscle metabolism is shifted towards a higher reliance on carbohydrates as a fuel, and intramyocellular lipid substrate stores are reduced. Moreover, in muscle cells of mountaineers returning from the Himalayas, we find accumulations of lipofuscin, believed to be a mitochondrial degradation product. Low mitochondrial contents are also observed in high-altitude natives such as Sherpas. In these subjects high-altitude performance seems to be improved by better coupling between ATP demand and supply pathways as well as better metabolite homeostasis. The hypoxia-inducible factor 1 (HIF-1) has been identified as a master regulator for the expression of genes involved in the hypoxia response, such as genes coding for glucose transporters, glycolytic enzymes and vascular endothelial growth factor (VEGF). HIF-1 achieves this by binding to hypoxia response elements in the promoter regions of these genes, whereby the increase of HIF-1 in hypoxia is the consequence of a reduced degradation of its dominant subunit HIF-1a. A further mechanism that seems implicated in the hypoxia response of muscle mitochondria is related to the formation of reactive oxygen species (ROS) in mitochondria during oxidative phosphorylation. How exactly ROS interfere with HIF-1a as well as MAP kinase and other signalling pathways is debated. The current evidence suggests that mitochondria themselves could be important players in oxygen sensing.

Impact of Hypoxia on the Metastatic Potential of Human Prostate Cancer Cells

International Nuclear Information System (INIS)

Dai Yao; Bae, Kyungmi; Siemann, Dietmar W.

2011-01-01

Purpose: Intratumoral hypoxia is known to be associated with radioresistance and metastasis. The present study examined the effect of acute and chronic hypoxia on the metastatic potential of prostate cancer PC-3, DU145, and LNCaP cells. Methods and Materials: Cell proliferation and clonogenicity were tested by MTT assay and colony formation assay, respectively. 'Wound-healing' and Matrigel-based chamber assays were used to monitor cell motility and invasion. Hypoxia-inducible factor 1 alpha (HIF-1α) expression was tested by Western blot, and HIF-1-target gene expression was detected by real-time polymerase chain reaction. Secretion of matrix metalloproteinases (MMPs) was determined by gelatin zymography. Results: When PC-3 cells were exposed to 1% oxygen (hypoxia) for various periods of time, chronic hypoxia (≥24 h) decreased cell proliferation and induced cell death. In contrast, prostate cancer cells exposed to acute hypoxia (≤6 h) displayed increased motility, clonogenic survival, and invasive capacity. At the molecular level, both hypoxia and anoxia transiently stabilized HIF-1α. Exposure to hypoxia also induced the early expression of MMP-2, an invasiveness-related gene. Treatment with the HIF-1 inhibitor YC-1 attenuated the acute hypoxia-induced migration, invasion, and MMP-2 activity. Conclusions: The length of oxygen deprivation strongly affected the functional behavior of all three prostate cancer cell lines. Acute hypoxia in particular was found to promote a more aggressive metastatic phenotype.

FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function

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Jensen, Kim Steen; Binderup, Tina; Jensen, Klaus Thorleif

2011-01-01

Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful...... tumour tissue in vivo and that FoxO3A short-hairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia....... reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes...... cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic...

Antioxidant mechanism of Rutin on hypoxia-induced pulmonary arterial cell proliferation.

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Li, Qian; Qiu, Yanli; Mao, Min; Lv, Jinying; Zhang, Lixin; Li, Shuzhen; Li, Xia; Zheng, Xiaodong

2014-11-18

Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.

Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation

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Qian Li

2014-11-01

Full Text Available Reactive oxygen species (ROS are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4 in pulmonary artery endothelial cells (PAECs. Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α. Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC, a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation.

Molecular characterization and mRNA expression of two key enzymes of hypoxia-sensing pathways in eastern oysters Crassostrea virginica (Gmelin): Hypoxia-inducible factor α (HIF-α) and HIF-prolyl hydroxylase (PHD)

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Piontkivska, Helen; Chung, J. Sook; Ivanina, Anna V.; Sokolov, Eugene P.; Techa, Sirinart; Sokolova, Inna M.

2010-01-01

Oxygen homeostasis is crucial for development, survival and normal function of all metazoans. A family of transcription factors called hypoxia-inducible factors (HIF) is critical in mediating the adaptive responses to reduced oxygen availability. The HIF transcription factor consists of a constitutively expressed β subunit and an oxygen-dependent α subunit; the abundance of the latter determines the activity of HIF and is regulated by a family of O2- and Fe2+-dependent enzymes prolyl hydroxylases (PHDs). Currently very little is known about the function of this important pathway and the molecular structure of its key players in hypoxia-tolerant intertidal mollusks including oysters, which are among the animal champions of anoxic and hypoxic tolerance and thus can serve as excellent models to study the role of HIF cascade in adaptations to oxygen deficiency. We have isolated transcripts of two key components of the oxygen sensing pathway - the oxygen-regulated HIF-α subunit and PHD - from an intertidal mollusk, the eastern oyster Crassostrea virginica, and determined the transcriptional responses of these two genes to anoxia, hypoxia and cadmium (Cd) stress. HIF-α and PHD homologs from eastern oysters C. virginica show significant sequence similarity and share key functional domains with the earlier described isoforms from vertebrates and invertebrates. Phylogenetic analysis shows that genetic diversification of HIF and PHD isoforms occurred within the vertebrate lineage indicating functional diversification and specialization of the oxygen-sensing pathways in this group, which parallels situation observed for many other important genes. HIF-α and PHD homologs are broadly expressed at the mRNA level in different oyster tissues and show transcriptional responses to prolonged hypoxia in the gills consistent with their putative role in oxygen sensing and the adaptive response to hypoxia. Similarity in amino acid sequence, domain structure and transcriptional

Resistance of juveniles of the Mediterranean pen shell, (Pinna nobilis) to hypoxia and interaction with warming

KAUST Repository

Basso, Lorena

2015-05-01

Low oxygen zones in coastal and open ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. Exposure of nearshore animals to hypoxic waters and increasing temperature may be stressful and lead to impaired physiological performance. Here, we evaluate the effect of low oxygen concentrations in interaction with increased temperature on juveniles of a large Mediterranean bivalve, Pinna nobilis. We examine the response of survival and oxygen consumption of juveniles placed in water with normal and low oxygen concentrations (100% and 40%, respectively) along an increased temperature gradient (24, 26, 28 and 30°C) during 4 days. To our knowledge, this is the first study on hypoxia and its combined effect with temperature on juveniles of this species. We show that the two stressors alone or in combination do not influence the physiological performance of juveniles for short periods (4 days). This result stands apart from a general trend pointing at ocean warming as additional stressor that could increase the vulnerability of benthic macrofauna to reduced oxygen concentrations. © 2015 Elsevier Ltd.

Resistance of juveniles of the Mediterranean pen shell, (Pinna nobilis) to hypoxia and interaction with warming

KAUST Repository

Basso, Lorena; Hendriks, Iris E.; Duarte, Carlos M.

2015-01-01

Low oxygen zones in coastal and open ecosystems have expanded in recent decades, a trend that will accelerate with climatic warming. Exposure of nearshore animals to hypoxic waters and increasing temperature may be stressful and lead to impaired physiological performance. Here, we evaluate the effect of low oxygen concentrations in interaction with increased temperature on juveniles of a large Mediterranean bivalve, Pinna nobilis. We examine the response of survival and oxygen consumption of juveniles placed in water with normal and low oxygen concentrations (100% and 40%, respectively) along an increased temperature gradient (24, 26, 28 and 30°C) during 4 days. To our knowledge, this is the first study on hypoxia and its combined effect with temperature on juveniles of this species. We show that the two stressors alone or in combination do not influence the physiological performance of juveniles for short periods (4 days). This result stands apart from a general trend pointing at ocean warming as additional stressor that could increase the vulnerability of benthic macrofauna to reduced oxygen concentrations. © 2015 Elsevier Ltd.

Drivers, mechanisms and long term variability of bottom seasonal hypoxia in the Black Sea north-western Shelf. Is there any recovery after eutrophication ?

Science.gov (United States)

Capet, Arthur; Beckers, Jean-Marie; Grégoire, Marilaure

2013-04-01

The Black Sea North-western shelf (NWS) is a shallow eutrophic area in which seasonal stratification of the water column isolates bottom waters from the atmosphere and prevents ventilation to compensate for the large consumption of oxygen, due to respiration in the bottom waters and in the sediments. A 3D coupled physical biogeochemical model is used to investigate the dynamics of bottom hypoxia in the Black Sea NWS at different temporal scales from seasonal to interannual (1981-2009) and to differentiate the driving factors (climatic versus eutrophication) of hypoxic conditions in bottom waters. Model skills are evaluated by comparison with 14500 in-situ oxygen measurements available in the NOAA World Ocean Database and the Black Sea Commission data. The choice of skill metrics and data subselections orientate the validation procedure towards specific aspects of the oxygen dynamics, and prove the model's ability to resolve the seasonal cycle and interannual variability of oxygen concentration as well as the spatial location of the oxygen depleted waters and the specific threshold of hypoxia. During the period 1981-2009, each year exhibits seasonal bottom hypoxia at the end of summer. This phenomenon essentially covers the northern part of the NWS, receiving large inputs of nutrients from the Danube, Dniestr and Dniepr rivers, and extends, during the years of severe hypoxia, towards the Romanian Bay of Constanta. In order to explain the interannual variability of bottom hypoxia and to disentangle its drivers, a statistical model (multiple linear regression) is proposed using the long time series of model results as input variables. This statistical model gives a general relationships that links the intensity of hypoxia to eutrophication and climate related variables. The use of four predictors allows to reproduce 78% of hypoxia interannual variability: the annual nitrate discharge (N), the sea surface temperature in the month preceding stratification (T ), the

[Effects of naloxone on the expression of stem cell factor and C-kit receptor in combined oxygen-glucose deprivation of primary cultured human embryonic neuron in vitro].

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Zhu, Bo; Li, Lan-ying; Lü, Guo-yi; Xue, Yu-liang; Ye, Tie-hu

2010-04-01

To explore the effects of naloxone on the expression of c-kit receptor (c-kit R) and its ligand stem cell factor (SCF) in human embryo neuronal hypoxic injury. Serum-free cerebral cortical cultures prepared from embryonic human brains were deprived of both oxygen and glucose which would set up an environment more likely with that of in vivo ischemic injury. Neurons in 24-well culture plates were randomly divided into four groups: control group, hypoxia group, naloxone 0.5 microg/ml group and naloxone 10 microg/ml group. MTT assay and biological analysis were performed to study the cell death and the changes of extracellular concentrations of lactate dehydrogenase (LDH) after combined oxygen-glucose deprivation. Neurons in 25 ml culture flasks were also randomly allocated into four groups as previously described. Intracellular total RNA were extracted at different time points: pre-hypoxia, immediately after hypoxia, and 3, 6, 12, and 24 hours after reoxygenation. The changes of SCF/c-kit R mRNA expression in hypoxic neurons treated with different concentrations of naloxone pre and post oxygen-glucose deprivation were determined with RT-PCR. The cell vitality detected by MTT assay decreased significantly in hypoxia group and naloxone 0.5 microg/ml group when compared with control group (Pcontrol group. Extracellular concentration of LDH significantly increased in hypoxia group (Pcontrol group, between naloxone 0.5 microg/ml and hypoxia group, or between naloxone 10 microg/ml and control group (all P>0.05). Immediately after oxygen-glucose deprivation, the expression of SCF/c-kit R mRNA increased significantly (Pcontrol group (Pglucose deprivation. Naloxone 0.5 microg/ml can attenuate cell injuries and regulate the expression of SCF/c-kit R. Naloxone may protect neurons by modulating the expressions of some cytokines.

An Assessment of Exercise Tolerance in Normobaric Hypoxia of Patients with Diabetes Mellitus Type 1

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Głuchowska Barbara

2014-09-01

Full Text Available Purpose. Physical activity is an integral part of the treatment of diabetes. The aim of the study was to assess aerobic capacity and cardiovascular-respiratory reactions to a single physical exercise with gradually increasing intensity in normobaric hypoxia in patients with Type 1 diabetes. Methods. The study was conducted on a sample of adults with Type 1 diabetes (GT1D, n = 13 and a randomly chosen healthy control (GK, n = 15. The study participants performed a progressive exercise test to exhaustion in normoxia (FiO2 ~ 20.90% and 7 days later in normobaric hypoxia (FiO2 ~ 15.14%. At rest, during exercise, and after completion of the test blood was drawn and physiological indicators were monitored. Results. Two-way ANOVA revealed a significant effect of hypoxia and physical exercise on blood glucose concentrations (F = 6.1 p < 0.01. In GT1D , lower glucose levels were observed in normobaric hypoxia compared with baseline and post-exercise levels in normoxia (p < 0.05. A tendency to increased maximal oxygen uptake and significantly higher minute pulmonary ventilation was observed in both groups in response to exercise and hypoxia. Conclusions. Physical activity and hypoxia may effectively control glucose homeostasis and increase cardiorespiratory adaptation to exercise in Type 1 diabetics.

[Simulated study of algal fatty acid degradation in hypoxia seawater-sediment interface along China coastal area].

Science.gov (United States)

Sui, Wei-Wei; Ding, Hai-Bing; Yang, Gui-Peng; Lu, Xiao-Lan; Li, Wen-Juan; Sun, Li-Qun

2013-11-01

Series of laboratory incubation experiments were conducted to simulate degradation of organic matter in sediment-seawater interface in hypoxia enviroments along China coastal area. Under four different redox conditions (oxygen saturation: 100%, 50%, 25% and 0%), degradations of seveal biomarkers originated from Skeletonema costatum, a typical red tide alage along China coastal area were tracked. By analyzing concentrations of four fatty acid biomarkers [14:0, 16:0, 16:1(7) and 20:5] obtained at various sampling time, results showed that their concentrations decreased significantly after 2-3 weeks' incubation. Then, their concentrations changed very slowly or very little. However, degradation of the four fatty acids varied dramatically in different incubation systems. Fatty acids 14:0, 16:1(7) and 20:5 were degraded completely in all incubation systems after two-month incubation, but 25% to 35% of 16:0 was reserved in the systems. Based on multi-G model, degradations of the four fatty acids were quantively described. The results indicated that all four fatty acids had fast-degraded and slow-degraded fractions. Their degradation rate constants (k(av)) ranged from 0.079 to 0.84 d(-1). The fastest degradation of 14:0 and 16:1 (7) occurred under 25% oxygen concentrations. For these two compounds, in the fastest degradation system, their k(av), values were 2.3 folds and 1.7 folds higher than those in the slowest degradation system [50% oxygen saturation for 14:0 and 100% oxygen saturation for 16:1(7)] respectively. The 16:0 was degraded fastest under the anoxic condition and slowest under the 50% oxygen saturation. The ratio of the two k(av)s was 2.1. The k(av)s of 20:5 had a positive relationship with oxygen saturations. Results of this study suggested that besides oxgen saturations, structure and features of organic compounds, roles of microbe in the envrioments and etc. might affect degradations of fatty acids in S. costatum in hypoxia sediment-seawater interface

An MRI Method To Map Tumor Hypoxia Using Red Blood Cells Loaded with a pO2-Responsive Gd-Agent.

Science.gov (United States)

Di Gregorio, Enza; Ferrauto, Giuseppe; Gianolio, Eliana; Lanzardo, Stefania; Carrera, Carla; Fedeli, Franco; Aime, Silvio

2015-08-25

Hypoxia is a typical hallmark of many solid tumors and often leads to therapy resistance and the development of a more aggressive cancer phenotype. Oxygen content in tissues has been evaluated using numerous different methods for several imaging modalities, but none has yet reached the required standard of spatial and temporal resolution. Magnetic Resonance Imaging (MRI) appears to be the technique of choice and several pO2-responsive probes have been designed for it over the years. In vivo translation is often hampered in Gd-relaxation agents as it is not possible to separate effects that arise from changes in local concentration from those associated with responsive properties. A novel procedure for the MRI based assessment of hypoxia is reported herein. The method relies on the combined use of Gd-DOTP- and Gd-HPDO3A-labeled red blood cells (RBCs) where the first probe acts as a vascular oxygenation-responsive agent, while the second reports the local labeled RBC concentration in a transplanted breast tumor mouse model. The MRI assessment of oxygenation state has been validated by photoacoustic imaging and ex vivo immunofluorescence. The method refines tumor staging in preclinical models and makes possible an accurate monitoring of the relationship between oxygenation and tumor growth.

Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications.

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Vaupel, Peter; Mayer, Arnulf

2014-01-01

Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.

Weakening of the radioprotective action of gas hypoxia with growth of ascitic tumors

Energy Technology Data Exchange (ETDEWEB)

Aytmagambetova, B Z; Shmakova, N L; Fadeyeva, T A

1975-06-27

It was shown previously that moderate hypoxia induced by breathing oxygen-poor air (5 percent O/sub 2/) reduces the lethal effect of the total irradiation of mice, while with local irradiation of tumors reduction of tumor growth rate is even more marked in hypoxia-protected animals than with irradiation of mice in normal air. This suggests the possible therapeutic application of hypoxia. It was found that acute gas hypoxia strongly retards radiation damage to bone marrow, both qualitatively (type of cells affected) and quantitatively. In addition, a definite weakening of the protective effect of hypoxia was observed, this being proportional to increase in tumor size. Planned future tests involving direct dynamic measurement of oxygen stress as a function of amount of ascites are expected to supply further information on reduction of radiosensitivity of normal tissues and on the selective intensification of tumor regression. Graphic data accompany the paper. (JPRS)

Hypoxia as a Biomarker and for Personalized Radiation Oncology

DEFF Research Database (Denmark)

Vordermark, Dirk; Horsman, Michael R

2016-01-01

Tumor hypoxia is a clinically relevant cause of radiation resistance. Direct measurements of tumor oxygenation have been performed predominantly with the Eppendorf histograph and these have defined the reduced prognosis after radiotherapy in poorly oxygenated tumors, especially head-and-neck canc...

Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.

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Yu, Lixia; Chen, Yuan; Wang, Weiguang; Xiao, Zhonghai; Hong, Yan

2016-08-04

Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective effects on hypoxia-induced memory deficit and AD related molecular events in mice. Adult male Kunming mice were assigned to five groups: normoxic control, hypoxic model (HH), hypoxia+vitamin B6/B12/folate (HB), hypoxia+choline (HC), hypoxia+vitamin B6/B12/folate+choline (HBC). Mice in the hypoxia, HB, HC, and HBC groups were exposed to hypobaric hypoxia for 8 h/day for 28 days in a decompression chamber mimicking 5500 meters of high altitude. Spatial and passive memories were assessed by radial arm and step-through passive test, respectively. Levels of tau and glycogen synthase kinase (GSK)-3β phosphorylation were detected by western blot. Homocysteine (Hcy) concentrations were determined using enzymatic cycling assay. Mice in the HH group exhibited significant spatial working and passive memory impairment, increased tau phosphorylation at Thr181, Ser262, Ser202/Thr205, and Ser396 in the cortex and hippocampus, and elevated Hcy levels compared with controls. Concomitantly, the levels of Ser9-phosphorylated GSK-3β were significantly decreased in brain after hypoxic treatment. Supplementations of vitamin B6/B12/folate+choline could significantly ameliorate the hypoxia-induced memory deficits, observably decreased Hcy concentrations in serum, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites through upregulating inhibitory Ser9-phosphorylated GSK-3β. Our finding give further insight into combined neuroprotective effects of vitamin B6, B12, folate, and choline on brain against hypoxia.

Drivers, mechanisms and long-term variability of seasonal hypoxia on the Black Sea northwestern shelf - is there any recovery after eutrophication?

Science.gov (United States)

Capet, A.; Beckers, J.-M.; Grégoire, M.

2013-06-01

The Black Sea northwestern shelf (NWS) is a shallow eutrophic area in which the seasonal stratification of the water column isolates the bottom waters from the atmosphere. This prevents ventilation from counterbalancing the large consumption of oxygen due to respiration in the bottom waters and in the sediments, and sets the stage for the development of seasonal hypoxia. A three-dimensional (3-D) coupled physical-biogeochemical model is used to investigate the dynamics of bottom hypoxia in the Black Sea NWS, first at seasonal and then at interannual scales (1981-2009), and to differentiate its driving factors (climatic versus eutrophication). Model skills are evaluated by a quantitative comparison of the model results to 14 123 in situ oxygen measurements available in the NOAA World Ocean and the Black Sea Commission databases, using different error metrics. This validation exercise shows that the model is able to represent the seasonal and interannual variability of the oxygen concentration and of the occurrence of hypoxia, as well as the spatial distribution of oxygen-depleted waters. During the period 1981-2009, each year exhibits seasonal bottom hypoxia at the end of summer. This phenomenon essentially covers the northern part of the NWS - which receives large inputs of nutrients from the Danube, Dniester and Dnieper rivers - and extends, during the years of severe hypoxia, towards the Romanian bay of Constanta. An index H which merges the aspects of the spatial and temporal extension of the hypoxic event is proposed to quantify, for each year, the intensity of hypoxia as an environmental stressor. In order to explain the interannual variability of H and to disentangle its drivers, we analyze the long time series of model results by means of a stepwise multiple linear regression. This statistical model gives a general relationship that links the intensity of hypoxia to eutrophication and climate-related variables. A total of 82% of the interannual variability

Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

International Nuclear Information System (INIS)

Vordermark, D.; Brown, J.M.

2003-01-01

Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1α responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1α overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a benefit from specific hypoxia

Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

Energy Technology Data Exchange (ETDEWEB)

Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

2003-12-01

Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

Formation of neutrophil extracellular traps under low oxygen level

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Katja Branitzki-Heinemann

2016-11-01

Full Text Available Since their discovery, neutrophil extracellular traps (NETs have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia inducible factor 1α (HIF-1α by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps. Since HIF-1α is a global regulator of the cellular response to low oxygen, we hypothesized that NET formation may be similarly increased under low oxygen conditions. Hypoxia occurs in tissues during infection or inflammation, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. Therefore, experiments were performed to characterize the formation of NETs under hypoxic oxygen conditions compared to normoxia. Human blood-derived neutrophils were isolated and incubated under normoxic (21% oxygen level and compared to hypoxic (1% conditions. Dissolved oxygen levels were monitored in the primary cell culture using a Fibox4-PSt3 measurement system. The formation of NETs was quantified by fluorescence microscopy in response to the known NET-inducer phorbol 12-myristate 13-acetate (PMA or S. aureus wildtype and a nuclease-deficient mutant. In contrast to our hypothesis, spontaneous NET formation of neutrophils incubated under hypoxia was distinctly reduced compared to control neutrophils incubated under normoxia. Furthermore, neutrophils incubated under hypoxia showed significantly reduced formation of NETs in response to PMA. Gene expression analysis revealed that mRNA level of hif-1α as well as hif-1α target genes was not altered. However, in good correlation to the decreased NET formation under hypoxia, the cholesterol content of the neutrophils was

Redox signaling in acute oxygen sensing

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Lin Gao

2017-08-01

Full Text Available Acute oxygen (O2 sensing is essential for individuals to survive under hypoxic conditions. The carotid body (CB is the main peripheral chemoreceptor, which contains excitable and O2-sensitive glomus cells with O2-regulated ion channels. Upon exposure to acute hypoxia, inhibition of K+ channels is the signal that triggers cell depolarization, transmitter release and activation of sensory fibers that stimulate the brainstem respiratory center to produce hyperventilation. The molecular mechanisms underlying O2 sensing by glomus cells have, however, remained elusive. Here we discuss recent data demonstrating that ablation of mitochondrial Ndufs2 gene selectively abolishes sensitivity of glomus cells to hypoxia, maintaining responsiveness to hypercapnia or hypoglycemia. These data suggest that reactive oxygen species and NADH generated in mitochondrial complex I during hypoxia are signaling molecules that modulate membrane K+ channels. We propose that the structural substrates for acute O2 sensing in CB glomus cells are “O2-sensing microdomains” formed by mitochondria and neighboring K+ channels in the plasma membrane. Keywords: Hypoxia, Acute oxygen sensing, Peripheral chemoreceptors, Carotid body, Adrenal medulla, Mitochondrial complex I, Reactive oxygen species (ROS, Pyridine nucleotides

The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

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Gabriella Teti

2018-01-01

Full Text Available Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2 imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α, which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.

Effect of Serum and Oxygen Concentration on Gene Expression and Secretion of Paracrine Factors by Mesenchymal Stem Cells

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Patrick Page

2014-01-01

Full Text Available Mesenchymal stem cells (MSC secrete paracrine factors that may exert a protective effect on the heart after coronary artery occlusion. This study was done to determine the effect of hypoxia and serum levels on the mRNA expression and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5% or 20% serum and in either normoxic (21% O2 or hypoxic (1% O2 conditions. Expression of mRNA for vascular endothelial growth factor (VEGF, monocyte chemotactic protein-1 (MCP-1, macrophage inflammatory protein-1α (MIP-1α, MIP-1β, and matrix metalloproteinase-2 (MMP-2 was determined by RT-qPCR. Secretion into the culture media was determined by ELISA. Hypoxia caused a reduction in gene expression for MCP-1 and an increase for VEGF (5% serum, MIP-1α, MIP-1β, and MMP-2. Serum reduction lowered gene expression for VEGF (normoxia, MCP-1 (hypoxia, MIP-1α (hypoxia, MIP-1β (hypoxia, and MMP-2 (hypoxia and increased gene expression for MMP-2 (normoxia. The level of secretion of these factors into the media generally paralleled gene expression with some exceptions. These data demonstrate that serum and oxygen levels have a significant effect on the gene expression and secretion of paracrine factors by MSC which will affect how MSC interact in vivo during myocardial ischemia.

A numerical analysis of biogeochemical controls with physical modulation on hypoxia during summer in the Pearl River estuary

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B. Wang

2017-06-01

Full Text Available A three-dimensional (3-D physical–biogeochemical coupled model was applied to explore the mechanisms controlling the dissolved oxygen (DO dynamics and bottom hypoxia during summer in the Pearl River estuary (PRE. By using the numerical oxygen tracers, we proposed a new method (namely the physical modulation method to quantify the contributions of boundary conditions and each source and sink process occurring in local and adjacent waters to the DO conditions. A mass balance analysis of DO based on the physical modulation method indicated that the DO conditions at the bottom layer were mainly controlled by the source and sink processes, among which the sediment oxygen demand (SOD at the water–sediment interface and the re-aeration at the air–sea interface were the two primary processes determining the spatial extent and duration of bottom hypoxia in the PRE. The SOD could cause a significant decrease in the bottom DO concentrations (averaged over July–August 2006 by over 4 mg L−1 on the shelf off the Modaomen sub-estuary, leading to the formation of a high-frequency zone of hypoxia (HFZ. However, the hypoxia that occurred in the HFZ was intermittent and distributed in a small area due to the combined effects of re-aeration and photosynthesis, which behaved as sources for DO and offset a portion of the DO consumed by SOD. The bottom DO concentrations to the west of the lower Lingdingyang Bay (i.e. the western shoal near Qi'ao Island were also largely affected by high SOD, but there was no hypoxia occurring there because of the influence of re-aeration. Specifically, re-aeration could lead to an increase in the bottom DO concentrations by ∼ 4.8 mg L−1 to the west of the lower Lingdingyang Bay. The re-aeration led to a strong vertical DO gradient between the surface and the lower layers. As a result, the majority (∼ 89 % of DO supplemented by re-aeration was transported to the lower layers through vertical diffusion and

Influence of oxygen concentration on ethylene removal using dielectric barrier discharge

Science.gov (United States)

Takahashi, Katsuyuki; Motodate, Takuma; Takaki, Koichi; Koide, Shoji

2018-01-01

Ethylene gas is decomposed using a dielectric barrier discharge plasma reactor for long-period preservation of fruits and vegetables. The oxygen concentration in ambient gas is varied from 2 to 20% to simulate the fruit and vegetable transport container. The experimental results show that the efficiency of ethylene gas decomposition increases with decreasing oxygen concentration. The reactions of ethylene molecules with ozone are analyzed by Fourier transform infrared spectrometry. The analysis results show that the oxidization process by ozone is later than that by oxygen atoms. The amount of oxygen atoms that contribute to ethylene removal increases with decreasing oxygen concentration because the reaction between oxygen radicals and oxygen molecules is suppressed at low oxygen concentrations. Ozone is completely removed and the energy efficiency of C2H4 removal is increased using manganese dioxide as a catalyst.

The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α protein levels in endothelial cells under hypoxia.

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Stefan K Alig

Full Text Available The tyrosine phosphatase SHP-1 negatively influences endothelial function, such as VEGF signaling and reactive oxygen species (ROS formation, and has been shown to influence angiogenesis during tissue ischemia. In ischemic tissues, hypoxia induced angiogenesis is crucial for restoring oxygen supply. However, the exact mechanism how SHP-1 affects endothelial function during ischemia or hypoxia remains unclear. We performed in vitro endothelial cell culture experiments to characterize the role of SHP-1 during hypoxia.SHP-1 knock-down by specific antisense oligodesoxynucleotides (AS-Odn increased cell growth as well as VEGF synthesis and secretion during 24 hours of hypoxia compared to control AS-Odn. This was prevented by HIF-1α inhibition (echinomycin and apigenin. SHP-1 knock-down as well as overexpression of a catalytically inactive SHP-1 (SHP-1 CS further enhanced HIF-1α protein levels, whereas overexpression of a constitutively active SHP-1 (SHP-1 E74A resulted in decreased HIF-1α levels during hypoxia, compared to wildtype SHP-1. Proteasome inhibition (MG132 returned HIF-1α levels to control or wildtype levels respectively in these cells. SHP-1 silencing did not alter HIF-1α mRNA levels. Finally, under hypoxic conditions SHP-1 knock-down enhanced intracellular endothelial reactive oxygen species (ROS formation, as measured by oxidation of H2-DCF and DHE fluorescence.SHP-1 decreases half-life of HIF-1α under hypoxic conditions resulting in decreased cell growth due to diminished VEGF synthesis and secretion. The regulatory effect of SHP-1 on HIF-1α stability may be mediated by inhibition of endothelial ROS formation stabilizing HIF-1α protein. These findings highlight the importance of SHP-1 in hypoxic signaling and its potential as therapeutic target in ischemic diseases.

Oxygen concentration diffusion analysis of lead-bismuth-cooled, natural-circulation reactor

International Nuclear Information System (INIS)

Ito, Kei; Sakai, Takaaki

2001-11-01

The feasibility study on fast breeder reactors in Japan has been conducted at JNC and related organizations. The Phase-I study has finished in March, 2001. During the Phase-I activity, lead-bismuth eutectic coolant has been selected as one of the possible coolant options and a medium-scale plant, cooled by a lead-bismuth natural circulation flow was studied. On the other side, it is known that lead-bismuth eutectic has a problem of structural material corrosiveness. It was found that oxygen concentration control in the eutectic plays an important role on the corrosion protection. In this report, we have developed a concentration diffusion analysis code (COCOA: COncentration COntrol Analysis code) in order to carry out the oxygen concentration control analysis. This code solves a two-dimensional concentration diffusion equation by the finite differential method. It is possible to simulate reaction of oxygen and hydrogen by the code. We verified the basic performance of the code and carried out oxygen concentration diffusion analysis for the case of an oxygen increase by a refueling process in the natural circulation reactor. In addition, characteristics of the oxygen control system was discussed for a different type of the control system as well. It is concluded that the COCOA code can simulate diffusion of oxygen concentration in the reactor. By the analysis of a natural circulation medium-scale reactor, we make clear that the ON-OFF control and PID control can well control oxygen concentration by choosing an appropriate concentration measurement point. In addition, even when a trouble occurs in the oxygen emission or hydrogen emission system, it observes that control characteristic drops away. It is still possible, however, to control oxygen concentration in such case. (author)

Adenosine concentration in the porcine coronary artery wall and A2A receptor involvement in hypoxia-induced vasodilatation.

Science.gov (United States)

Frøbert, Ole; Haink, Gesine; Simonsen, Ulf; Gravholt, Claus H; Levin, Max; Deussen, Andreas

2006-01-15

We tested whether hypoxia-induced coronary artery dilatation could be mediated by an increase in adenosine concentration within the coronary artery wall or by an increase in adenosine sensitivity. Porcine left anterior descendent coronary arteries, precontracted with prostaglandin F(2alpha) (10(-5) M), were mounted in a pressure myograph and microdialysis catheters were inserted into the tunica media. Dialysate adenosine concentrations were analysed by HPLC. Glucose, lactate and pyruvate were measured by an automated spectrophotometric kinetic enzymatic analyser. The exchange fraction of [(14)C]adenosine over the microdialysis membrane increased from 0.32 +/- 0.02 to 0.46 +/- 0.02 (n = 4, P lactate/pyruvate ratio was significantly increased in hypoxic arteries but did not correlate with adenosine concentration. We conclude that hypoxia-induced coronary artery dilatation is not mediated by increased adenosine produced within the artery wall but might be facilitated by increased adenosine sensitivity at the A(2A) receptor level.

Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

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Peter Vaupel

2014-03-01

Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

Quantitative analysis of brain metabolites concentrations using MR spectroscopy in acute hypoxia ischemic encephalopathy

International Nuclear Information System (INIS)

Xiao Yeyu; Wang HaiYu; Shen Zhiwei; Lin Yan; Chen Yaowen; Xiao Gang; Wu Renhua

2010-01-01

Objective: To evaluate the absolute quantification of brain metabolites concentrations using external standard MRS in acute hypoxia ischemia encephalopathy (HIE) piglet model. Method: Eight 7-day-old healthy piglets were subjected to insult of hypoxia ischemia (HI). The animals and an external standard phantom containing detectable metabolites of known concentrations were studied on a 1.5 T GE Signa scanner. The single-voxel proton magnetic resonance spectroscopy ( 1 H-MRS) data were processed using LCModel software, and the quantification of N-acetylaspartate (NAA), creatine (Cr) and lactate (Lac) were accomplished. Multivariate analysis of variance was performed to compare the NAA, Cr, Lac concentration differences in the brains of piglets pre- and post-HI (0h). In addition, the dynamic changes of brain metabolites concentrations of 2 HIE piglets were observed at the time points of 0 h and 2 h. Results: One piglet was excluded because it was over anesthetized to death. Seven piglets' data were analyzed. The concentrations of NAA pre- and post-HI were (6.86±0.49) mmol/kg and (5.73±0.88) mmol/kg respectively, they were (4.65±0.73) mmol/kg and (4.40±0.80) mmol/kg for Cr; and were 0.00 mmol/kg and (0.43±0.39) mmol/kg for Lac. After HI, decreased NAA concentration immediately was observed, and it was of statistical significance (F=8.608, P=0.013). The concentration of Cr was insignificantly decreased (F=0.379, P=0.550). The concentration of Lac was increased, and the difference was of statistical significance (F=8.600, P=0.013). Dynamic observation showed a Lac peak immediately after HI and it decreased after 2 h post-HI. Conclusions: External standard MRS using LCModel has great value in the quantitative analysis of brain metabolites. The changes of NAA and Lac concentrations are sensitive to reflect the early metabolic change of acute HIE. (authors)

The infectious hypoxia: occurrence and causes during Shigella infection.

Science.gov (United States)

Arena, Ellen T; Tinevez, Jean-Yves; Nigro, Giulia; Sansonetti, Philippe J; Marteyn, Benoit S

2017-03-01

Hypoxia is defined as a tissue oxygenation status below physiological needs. During Shigella infection, an infectious hypoxia is induced within foci of infection. In this review, we discuss how Shigella physiology and virulence are modulated and how the main recruited immune cells, the neutrophils, adapt to this environment. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

[Oxidative power and intracellular distribution of mitochondria control cell oxygen regime when arterial hypoxemia occurs].

Science.gov (United States)

Liabakh, E G; Lissov, P N

2012-01-01

The regulatory impact of the mitochondria spatial distribution and enlargement in their oxidative power qO2 on the tissue oxygenation of skeletal muscle during hypoxia were studied. Investigations were performed by the mathematical modeling of 3D O2 diffusion-reaction in muscle fiber. The oxygen consumption rate VO2 and tissue pO2 were analyzed in response to a decrease in arterial blood oxygen concentration from 19.5 to 10 vol. % at a moderate load (3.5 ml/min per 100 g). The cells with evenly (case 1) and unevenly (case 2) distributed mitochondria were considered. According to calculations due to a rise in mitochondria oxidative power from 3.5 to 6.5 ml/min. per 100 g of tissue it is possible to maintain muscle oxygen V(O2) at constant level of 3.5 ml/min per 100 g despite a decrease in O2 delivery. Minimum value of tissue pO2 was about 0 and an area of hypoxia appeared inside the cell in case 1. But hypoxia disappeared and minimum value of pO2 increased from 0 to 4 mm Hg if mitochondria were distributed unevenly (case 2). It is shown that the possibilities of such regulation were limited and depended on the ratio of "the degree of hypoxemia--the level of oxygen delivery." It was assumed that an increase in mitochondria enzyme activity and mitochondria migration to the places of the greatest oxygen consumption rate can improve oxygen regime in the cells in terms of their adaptation to hypoxia. It is possible that changes in mitochondrial oxidative power and their intracellular redistribution may be considered as a new dimension in regulation of cell oxygen regime.

Multiple roles of hypoxia in ovarian function: roles of hypoxia-inducible factor-related and -unrelated signals during the luteal phase

OpenAIRE

Nishimura, Ryo; Okuda, Kiyoshi

2015-01-01

There is increasing interest in the role of oxygen conditions in the microenvironment of organs because of the discovery of a hypoxia-specific transcription factor, namely hypoxia-inducible factor (HIF) 1. Ovarian function has several phases that change day by day, including ovulation, follicular growth and corpus luteum formation and regression. These phases are regulated by many factors, including pituitary hormones and local hormones, such as steroids, peptides and cytokines, as well as ox...

Drivers, mechanisms and long-term variability of seasonal hypoxia on the Black Sea northwestern shelf – is there any recovery after eutrophication?

Directory of Open Access Journals (Sweden)

A. Capet

2013-06-01

Full Text Available The Black Sea northwestern shelf (NWS is a shallow eutrophic area in which the seasonal stratification of the water column isolates the bottom waters from the atmosphere. This prevents ventilation from counterbalancing the large consumption of oxygen due to respiration in the bottom waters and in the sediments, and sets the stage for the development of seasonal hypoxia. A three-dimensional (3-D coupled physical–biogeochemical model is used to investigate the dynamics of bottom hypoxia in the Black Sea NWS, first at seasonal and then at interannual scales (1981–2009, and to differentiate its driving factors (climatic versus eutrophication. Model skills are evaluated by a quantitative comparison of the model results to 14 123 in situ oxygen measurements available in the NOAA World Ocean and the Black Sea Commission databases, using different error metrics. This validation exercise shows that the model is able to represent the seasonal and interannual variability of the oxygen concentration and of the occurrence of hypoxia, as well as the spatial distribution of oxygen-depleted waters. During the period 1981–2009, each year exhibits seasonal bottom hypoxia at the end of summer. This phenomenon essentially covers the northern part of the NWS – which receives large inputs of nutrients from the Danube, Dniester and Dnieper rivers – and extends, during the years of severe hypoxia, towards the Romanian bay of Constanta. An index H which merges the aspects of the spatial and temporal extension of the hypoxic event is proposed to quantify, for each year, the intensity of hypoxia as an environmental stressor. In order to explain the interannual variability of H and to disentangle its drivers, we analyze the long time series of model results by means of a stepwise multiple linear regression. This statistical model gives a general relationship that links the intensity of hypoxia to eutrophication and climate-related variables. A total of 82% of the

Impact of Hypoxia on Startle Response (C-start) of Fish in a Tropical Urban Estuary

Science.gov (United States)

Sánchez-García, M.; Zottoli, S. J.; Roberson, L.

2016-02-01

Hypoxic zones have become more prevalent in marine ecosystems as a result of physical changes to the coastal zone, pollution and eutrophication, and are expected to increase in prevalence with climate change. While some studies have examined the behavioral effects of hypoxia on coastal fishes in temperate and sub-tropical zones, none have focused on tropical coastal zones. Behavioral changes may affect fish survival, predator-prey interactions and ultimately ecosystem structure. Through behavioral endpoints we evaluated the effects of non-lethal levels of hypoxia on estuarine fish collected from the tropical Condado Lagoon, San Juan P.R, in a laboratory setting. Two groups of 10 fishes were placed individually in a sound test chamber and oxygen concentrations were modulated from a pre-treatment at 100% oxygen to increasing levels of hypoxia (80, 70, & 60%), followed by a reversal treatment (100%) to test for recovery of pretreatment behavior. An abrupt sound stimulus was used to elicit a startle response, a quantifiable biological endpoint, while recording with a high speed camera. This approach can lend valuable insight into changes in the central nervous system and effects of anthropogenic inputs on tropical ecosystems at the individual- and population-level. We found that hypoxic conditions significantly decrease fish responsiveness; fish startled only half the time at 80% O2 and dropped as much as 61% at 60% O2. Additionally, responsiveness in reversal tests were significantly lower than under pre-treatment conditions. These results indicate that hypoxia may have long-term or possibly permanent effects, even under relatively mild hypoxia conditions common to tropical estuaries. Future work will aim to understand if the startle response can be regained after a hypoxic event.

The effect of lidocaine on neutrophil CD11b/CD18 and endothelial ICAM-1 expression and IL-1beta concentrations induced by hypoxia-reoxygenation.

LENUS (Irish Health Repository)

Lan, W

2012-02-03

BACKGROUND: Lidocaine has actions potentially of benefit during ischaemia-reperfusion. Neutrophils and endothelial cells have an important role in ischaemia-reperfusion injury. METHODS: Isolated human neutrophil CD11b and CD18, and human umbilical vein endothelial cell (HUVEC) ICAM-1 expression and supernatant IL-1beta concentrations in response to hypoxia-reoxygenation were studied in the presence or absence of different concentrations of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)). Adhesion molecule expression was quantified by flow cytometry and IL- 1beta concentrations by ELISA. Differences were assessed with analysis of variance and Student-Newman-Keuls as appropriate. Data are presented as mean+\\/-SD. RESULTS: Exposure to hypoxia-reoxygenation increased neutrophil CD11b (94.33+\\/-40.65 vs. 34.32+\\/-6.83 mean channel fluorescence (MCF), P = 0.02), CD18 (109.84+\\/-35.44 vs. 59.05+\\/-6.71 MCF, P = 0.03) and endothelial ICAM-1 (146.62+\\/-16.78 vs. 47.29+\\/-9.85 MCF, P < 0.001) expression compared to normoxia. Neutrophil CD18 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (71.07+\\/-10.14 vs. 109.84+\\/-35.44 MCF, P = 0.03). Endothelial ICAM-1 expression on exposure to hypoxia-reoxygenation was less in lidocaine (0.005 mg mL(-1)) treated cells compared to control (133.25+\\/-16.05 vs. 146.62+\\/-16.78 MCF, P = 0.03). Hypoxia-reoxygenation increased HUVEC supernatant IL-1beta concentrations compared to normoxia (3.41+\\/-0.36 vs. 2.65+\\/-0.21 pg mL(-1), P = 0.02). Endothelial supernatant IL-1beta concentrations in lidocaine-treated HUVECs were similar to controls. CONCLUSIONS: Lidocaine at clinically relevant concentrations decreased neutrophil CD18 and endothelial ICAM-1 expression but not endothelial IL-1beta concentrations.

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

Science.gov (United States)

Ren, Si-Hua; He, Yu-Xin; Ma, Yi-Ran; Jin, Jing-Chun; Kang, Dan

2016-02-01

To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

[Acute mild hypoxia impairment of dynamic cerebral autoregulation assessed by spectral analysis and thigh-cuff deflation].

Science.gov (United States)

Katsukawa, Hajime; Ogawa, Yojiro; Aoki, Ken; Yanagida, Ryo; Iwasaki, Kenichi

2012-01-01

Acute hypoxia may impair dynamic cerebral autoregulation. However, previous studies have been controversial. The difference in methods of estimation of dynamic cerebral autoregulation is reported to be responsible for conflicting reports. We, therefore, conducted this study using two representative methods of estimation of dynamic cerebral autoregulation to test our hypothesis that dynamic cerebral autoregulation is impaired during acute exposure to mild hypoxia. Eleven healthy men were exposed to 15% oxygen concentration for two hours. They were examined under normoxia (21% O(2)) and hypoxia (15% O(2)). The mean arterial pressure (MAP) in the radial artery was measured by tonometry, and cerebral blood flow velocity (CBFv) in the middle cerebral artery was measured by transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was assessed by spectral and transfer function analyses of beat-by-beat changes in MAP and CBFv. Moreover, the dynamic rate of regulation and percentage restoration of CBFv were estimated when a temporal decrease in arterial pressure was induced by thigh-cuff deflation. Arterial oxygen saturation decreased significantly during hypoxia (97±0% to 88±1%), whereas respiratory rate was unchanged, as was steady-state CBFv. With 15% O(2), the very-low-frequency power of CBFv variability increased significantly. Transfer function coherence (0.40±0.02 to 0.53±0.05) and gain (0.51±0.07 cm/s/mmHg to 0.79±0.11 cm/s/mmHg) in the very-low-frequency range increased significantly. Moreover, the percentage restoration of CBF velocity determined by thigh-cuff deflation decreased significantly during hypoxia (125±25% to 65±8%). Taken together, these results obtained using two representative methods consistently indicate that mild hypoxia impairs dynamic cerebral autoregulation.

Prolonged hypoxia modulates platelet activating factor receptor-mediated responses by fetal ovine pulmonary vascular smooth muscle cells.

Science.gov (United States)

Renteria, Lissette S; Raj, J Usha; Ibe, Basil O

2010-12-01

Hypoxia augments PAF receptor (PAFr) binding and PAFr protein expression in venous SMC (SMC-PV). We compared effect of acute and prolonged hypoxia (pO(2)<40 torr) on PAFr-mediated responses in arterial SMC (SMC-PA) and SMC-PV. Cells were studied for 30 min (acute) or for 48 h (prolonged) hypoxia and compared to normoxic (pO(2) ~100 torr) conditions. PAF binding was quantified in fmol/10(6) cells (mean ± SEM). PAF binding in normoxia were SMC-PA, 5.2 ± 0.2 and in SMC-PV, 19.3 ± 1.1; values in acute hypoxia were SMC-PA, 7.7 ± 0.4 and in SMC-PV, 27.8 ± 1.7. Prolonged hypoxia produced 6-fold increase in binding in SMC-PA, but only 2-fold increase in SMC-PV, but binding in SMC-PV was still higher. Acute hypoxia augmented inositol phosphate release by 50% and 40% in SMC-PA and SMC-PV, respectively. During normoxia, PAFr mRNA expression by both cell types was similar, but expression in hypoxia by SMC-PA was greater. In SMC-PA, hypoxia and PAF augmented intracellular calcium flux. Re-exposure of cells to 30 min normoxia after 48 h hypoxia decreased binding by 45-60%, suggesting immediate down-regulation of hypoxia-induced PAFr-mediated effects. We speculate that re-oxygenation immediately reverses hypoxia effect probably due to oxygen tension-dependent reversibility of PAFr activation and suggest that exposure of the neonate to prolonged state of hypoxia will vilify oxygen exchange capacity of the neonatal lungs. Copyright © 2010 Elsevier Inc. All rights reserved.

Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

Science.gov (United States)

Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

2016-01-01

We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

Directory of Open Access Journals (Sweden)

Kiminori Sada

Full Text Available We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs, cellular hypoxia increased after incubation with high glucose (HG. A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1, a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Glycogen synthesis is induced in hypoxia by the hypoxia-inducible factor and promotes cancer cell survival

Directory of Open Access Journals (Sweden)

Joffrey ePelletier

2012-02-01

Full Text Available The hypoxia-inducible factor 1 (HIF-1, in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1, were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these hypoxia-preconditioned cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO2 acts as an alarm that prepares the cells to face subsequent nutrient depletion and to survive.

Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

Energy Technology Data Exchange (ETDEWEB)

Pelletier, Joffrey; Bellot, Grégory [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France); Gounon, Pierre; Lacas-Gervais, Sandra [Centre Commun de Microscopie Appliquée, University of Nice-Sophia Antipolis, Nice (France); Pouysségur, Jacques; Mazure, Nathalie M., E-mail: mazure@unice.fr [Institute of Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, University of Nice-Sophia Antipolis, Nice (France)

2012-02-28

The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO{sub 2} acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

Glycogen Synthesis is Induced in Hypoxia by the Hypoxia-Inducible Factor and Promotes Cancer Cell Survival

International Nuclear Information System (INIS)

Pelletier, Joffrey; Bellot, Grégory; Gounon, Pierre; Lacas-Gervais, Sandra; Pouysségur, Jacques; Mazure, Nathalie M.

2012-01-01

The hypoxia-inducible factor 1 (HIF-1), in addition to genetic and epigenetic changes, is largely responsible for alterations in cell metabolism in hypoxic tumor cells. This transcription factor not only favors cell proliferation through the metabolic shift from oxidative phosphorylation to glycolysis and lactic acid production but also stimulates nutrient supply by mediating adaptive survival mechanisms. In this study we showed that glycogen synthesis is enhanced in non-cancer and cancer cells when exposed to hypoxia, resulting in a large increase in glycogen stores. Furthermore, we demonstrated that the mRNA and protein levels of the first enzyme of glycogenesis, phosphoglucomutase1 (PGM1), were increased in hypoxia. We showed that induction of glycogen storage as well as PGM1 expression were dependent on HIF-1 and HIF-2. We established that hypoxia-induced glycogen stores are rapidly mobilized in cells that are starved of glucose. Glycogenolysis allows these “hypoxia-preconditioned” cells to confront and survive glucose deprivation. In contrast normoxic control cells exhibit a high rate of cell death following glucose removal. These findings point to the important role of hypoxia and HIF in inducing mechanisms of rapid adaptation and survival in response to a decrease in oxygen tension. We propose that a decrease in pO 2 acts as an “alarm” that prepares the cells to face subsequent nutrient depletion and to survive.

Oxygen-Partial-Pressure Sensor for Aircraft Oxygen Mask

Science.gov (United States)

Kelly, Mark; Pettit, Donald

2003-01-01

A device that generates an alarm when the partial pressure of oxygen decreases to less than a preset level has been developed to help prevent hypoxia in a pilot or other crewmember of a military or other high-performance aircraft. Loss of oxygen partial pressure can be caused by poor fit of the mask or failure of a hose or other component of an oxygen distribution system. The deleterious physical and mental effects of hypoxia cause the loss of a military aircraft and crew every few years. The device is installed in the crewmember s oxygen mask and is powered via communication wiring already present in all such oxygen masks. The device (see figure) includes an electrochemical sensor, the output potential of which is proportional to the partial pressure of oxygen. The output of the sensor is amplified and fed to the input of a comparator circuit. A reference potential that corresponds to the amplified sensor output at the alarm oxygen-partial-pressure level is fed to the second input of the comparator. When the sensed partial pressure of oxygen falls below the minimum acceptable level, the output of the comparator goes from the low state (a few millivolts) to the high state (near the supply potential, which is typically 6.8 V for microphone power). The switching of the comparator output to the high state triggers a tactile alarm in the form of a vibration in the mask, generated by a small 1.3-Vdc pager motor spinning an eccentric mass at a rate between 8,000 and 10,000 rpm. The sensation of the mask vibrating against the crewmember s nose is very effective at alerting the crewmember, who may already be groggy from hypoxia and is immersed in an environment that is saturated with visual cues and sounds. Indeed, the sensation is one of rudeness, but such rudeness could be what is needed to stimulate the crewmember to take corrective action in a life-threatening situation.

The relationship between temporal variation of hypoxia, polarographic measurements and predictions of tumour response to radiation

Science.gov (United States)

Toma-Dasu, Iuliana; Dasu, Alexandru; Karlsson, Mikael

2004-10-01

The polarographic oxygen sensor is one of the most used devices for in vivo measurements of oxygen and many other measurement techniques for measuring tumour hypoxia are correlated with electrode measurements. Little is known however about the relationship between electrode measurements and the real tissue oxygenation. This paper investigates the influence of the temporal change of the hypoxic pattern on the electrode measurements and the tumour response. Electrode measurements and tumour response were simulated using a computer program that allows both the calculation of the tissue oxygenation with respect to the two types of hypoxia that might arise in tumours and the virtual insertion of the electrode into the tissue. It was therefore possible to control the amount of each type of hypoxia in order to investigate their influence on the measurement results. Tissues with several vascular architectures ranging from well oxygenated to poorly oxygenated were taken into consideration as might be seen in practice. The influence of the electrode measurements on the treatment outcome was estimated by calculating the tumour control probability for the tumours characterized either by the real or by the measured tumour oxygenation. We have simulated electrode oxygen measurements in different types of tissues, covering a wide range of tumour oxygenations. The results of the simulations showed that the measured distribution depends on the details of the vascular network and not on the type of hypoxia. We have also simulated the effects of the temporal change of the acute hypoxic pattern due to the opening and the closure of different blood vessels during a full fractionated treatment. The results of this simulation suggested that the temporal variation of the hypoxic pattern does not lead to significantly different results for the electrode measurements or the predicted tumour control probabilities. In conclusion, it was found that the averaging effect of the electrode leads

IMPACT OF OXYGEN CONCENTRATION ON ZEBRA MUSSEL MORTALITY

Energy Technology Data Exchange (ETDEWEB)

Daniel P. Molloy

2003-01-27

These tests have indicated that the bacterium Pseudomonas fluorescens strain CL0145A is effective at killing zebra mussels in environments having dissolved oxygen (DO) concentrations ranging from very low to very high. The results suggest that the highest mussel kill can be achieved in moderately to highly aerated environments, while kill may be 0-20% lower under conditions of very low oxygen. For example, under highly oxygenated conditions 97% kill was achieved while conditions having low DO produced 79% mussel kill. Service water measured in a local power plant indicated that DO concentrations were in the range of 8-9 ppm (e.g., highly aerated) within their pipes. Therefore, we will not expect to see decreases in the efficacy of CL0145A treatments due to oxygen levels within such power plant pipes.

IMPACT OF OXYGEN CONCENTRATION ON ZEBRA MUSSEL MORTALITY

International Nuclear Information System (INIS)

Molloy, Daniel P.

2003-01-01

These tests have indicated that the bacterium Pseudomonas fluorescens strain CL0145A is effective at killing zebra mussels in environments having dissolved oxygen (DO) concentrations ranging from very low to very high. The results suggest that the highest mussel kill can be achieved in moderately to highly aerated environments, while kill may be 0-20% lower under conditions of very low oxygen. For example, under highly oxygenated conditions 97% kill was achieved while conditions having low DO produced 79% mussel kill. Service water measured in a local power plant indicated that DO concentrations were in the range of 8-9 ppm (e.g., highly aerated) within their pipes. Therefore, we will not expect to see decreases in the efficacy of CL0145A treatments due to oxygen levels within such power plant pipes

Oxygenation decreases elastin secretion from rat ductus arteriosus smooth muscle cells.

Science.gov (United States)

Kawakami, Shoji; Minamisawa, Susumu

2015-08-01

The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The oxygen concentration in the blood rises after birth, and in the DA this increase in oxygen concentration causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling of various vessels. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA due to production of proteins secreted from DA smooth muscle cells (SMC). Liquid chromatography-tandem mass spectrometry was used to comprehensively investigate the secreted proteins in the supernatant of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic conditions (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMC. On reverse transcription-polymerase chain reaction, the expression of elastin mRNA was not significantly changed in DA SMC from hypoxic to normoxic conditions. Given that elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, and that a rise in oxygen concentration reduced the secretion of elastin, this suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, and therefore may play a role in DA structural remodeling after birth. © 2015 Japan Pediatric Society.

Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes

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Shih-Han Kao

2016-02-01

Full Text Available Tumor hypoxia is a pathophysiologic outcome of disrupted microcirculation with inadequate supply of oxygen, leading to enhanced proliferation, epithelial-mesenchymal transition (EMT, metastasis, and chemo-resistance. Epigenetic changes induced by hypoxia are well documented, and they lead to tumor progression. Recent advances show that DNA demethylation mediated by the Ten-eleven translocation (TET proteins induces major epigenetic changes and controls key steps of cancer development. TET enzymes serve as 5mC (5-methylcytosine-specific dioxygenases and cause DNA demethylation. Hypoxia activates the expression of TET1, which also serves as a co-activator of HIF-1α transcriptional regulation to modulate HIF-1α downstream target genes and promote epithelial-mesenchymal transition. As HIF is a negative prognostic factor for tumor progression, hypoxia-activated prodrugs (HAPs may provide a favorable therapeutic approach to lessen hypoxia-induced malignancy.

Hypoxia Pathway Proteins As Central Mediators of Metabolism in the Tumor Cells and Their Microenvironment

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Sundary Sormendi

2018-01-01

Full Text Available Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation. However, as the modulated action of hypoxia-inducible factors or the oxygen sensors (prolyl hydroxylase domain-containing enzymes can also lead to changes in enzyme expression, these metabolic changes can also be indirect. With this review, we want to summarize our current knowledge of the hypoxia-induced changes in metabolism during cancer development, how they are affected in the tumor cells and in the cells of the microenvironment, most prominently in immune cells.

Hypoxia-based strategies for regenerative dentistry-Views from the different dental fields.

Science.gov (United States)

Müller, Anna Sonja; Janjić, Klara; Lilaj, Bledar; Edelmayer, Michael; Agis, Hermann

2017-09-01

The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting. In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dislocation behavior of surface-oxygen-concentration controlled Si wafers

International Nuclear Information System (INIS)

Asazu, Hirotada; Takeuchi, Shotaro; Sannai, Hiroya; Sudo, Haruo; Araki, Koji; Nakamura, Yoshiaki; Izunome, Koji; Sakai, Akira

2014-01-01

We have investigated dislocation behavior in the surface area of surface-oxygen-concentration controlled Si wafers treated by a high temperature rapid thermal oxidation (HT-RTO). The HT-RTO process allows us to precisely control the interstitial oxygen concentration ([O i ]) in the surface area of the Si wafers. Sizes of rosette patterns, generated by nano-indentation and subsequent thermal annealing at 900 °C for 1 h, were measured for the Si wafers with various [O i ]. It was found that the rosette size decreases in proportion to the − 0.25 power of [O i ] in the surface area of the Si wafers, which were higher than [O i ] of 1 × 10 17 atoms/cm 3 . On the other hand, [O i ] of lower than 1 × 10 17 atoms/cm 3 did not affect the rosette size very much. These experimental results demonstrate the ability of the HT-RTO process to suppress the dislocation movements in the surface area of the Si wafer. - Highlights: • Surface-oxygen-concentration controlled Si wafers have been made. • The oxygen concentration was controlled by high temperature rapid thermal oxidation. • Dislocation behavior in the surface area of the Si wafers has been investigated. • Rosette size decreased with increasing of interstitial oxygen atoms. • The interstitial oxygen atoms have a pinning effect of dislocations at the surface

Research Report: Intermittent hypobaric hypoxia and hyperbaric oxygen on GAP-43 in the rat carotid body.

Science.gov (United States)

Peng, Zhengwu; Fan, Juan; Liu, Ling; Kuang, Fang; Xue, Fen; Wang, Bairen

2015-01-01

Adaptive changes in the carotid body (CB) including the expression of the growth-associated protein-43 (GAP-43) have been studied in response to low, but not high, oxygen exposure. Expression of GAP-43 in the CB of rats under different atmospheric pressures and oxygen partial pressure (PO2) conditions was investigated. Mature male Sprague-Dawley rats were exposed to intermittent hypobaric hypoxia (IHH, 0, 1, 2 and 3 weeks), intermittent hyperbaric oxygen (IHBO2, 0, 1, 5 and 10 days, sacrificed six hours or 24 hours after the last HBO2 exposure), and intermittent hyperbaric normoxia (IHN, same treatment pattern as IHBO2). GAP-43 was highly expressed (mainly in type I cells) in the CB of normal rats. IHH u-regulated GAP-43 expression in the CB with significant differences (immunohistochemical staining [IHC]: F(3,15)=40.64, P GAP-43 expression in the CB was inhibited by IHBO2 (controls vs. IHBO2 groups, IHC: F(6,30) = 15.85, P GAP-43 expression were found for IHN. These findings indicated that different PO2 conditions, but not air pressures, played an important role in the plasticity of the CB, and that GAP-43 might be a viable factor for the plasticity of the CB.

[Study on intermittent hypoxia in children sleep apnea hypopnea syndrome model and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels in serum].

Science.gov (United States)

Hou, Jin; Yan, Jing; Kang, Quan-qing

2012-03-01

Using rats fed in intermittent hypoxia environment to study the relationship between sleep apnea hypopnea syndrome (SAHS) of children and growth retardation. The hypoxic chamber was designed and manufactured, the control of intermittent hypoxia was achieved. Twenty-four rats were randomly divided into three groups: mild and severe hypoxia group, and control group. In control group, the animals were normally fed, without interruption. The animals in other two groups were kept in the cabin, simulated mild and severe intermittent hypoxia conditions 8-hour a day, a total of 35 days. According to the results of preliminary experiments, the concentration of intermittent hypoxia and frequency were determined. The animals with mild hypoxia events occurred nearly six times per hour, the average minimum oxygen saturation dropped to 0.853, the animals with severe hypoxia events occurred nearly 24 times per hour, the average minimum oxygen saturation dropped to 0.776. Body mass and length were measured before and after experiment. The serum insulin-like growth factor (IGF)-1 and insulin-like growth factor binding protein (IGFBP)-3 expression were tested from venous blood by enzyme-linked immunosorbent assay (ELISA). The length and body mass of rats in three groups before and after experiment were not statistically different (P>0.05). Before the experiment the serum IGF-1 and IGFBP-3 levels were not significantly different (P>0.05). 35 d after the experiment, the serum IGF-1 (x±s, the same below) in the control group, mild hypoxia and severe hypoxia were (60.0±18.5) ng/ml, (40.6±9.9) ng/ml and (13.1±8.6) ng/ml, F=25.840, Phypoxia increased (Papnea hypopnea syndrome, the intermittent hypoxia in young rats does not show physical growth retardation, but the serum IGF-1, IGFBP-3 levels decreased with the increase of hypoxia and decline of oxygen saturation.

2007 Hypoxia Watch Bottom CTD Station Locations

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National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2004 Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2005 Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2002 Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2003 Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2001 Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Reducing body fat with altitude hypoxia training in swimmers: role of blood perfusion to skeletal muscles.

Science.gov (United States)

Chia, Michael; Liao, Chin-An; Huang, Chih-Yang; Lee, Wen-Chih; Hou, Chien-Wen; Yu, Szu-Hsien; Harris, M Brennan; Hsu, Tung-Shiung; Lee, Shin-Da; Kuo, Chia-Hua

2013-02-28

Swimmers tend to have greater body fat than athletes from other sports. The purpose of the study was to examine changes in body composition after altitude hypoxia exposure and the role of blood distribution to the skeletal muscle in swimmers. With a constant training volume of 12.3 km/day, young male swimmers (N = 10, 14.8 ± 0.5 years) moved from sea-level to a higher altitude of 2,300 meters. Body composition was measured before and after translocation to altitude using dual-energy X-ray absorptiometry (DXA) along with 8 control male subjects who resided at sea level for the same period of time. To determine the effects of hypoxia on muscle blood perfusion, total hemoglobin concentration (THC) was traced by near-infrared spectroscopy (NIRS) in the triceps and quadriceps muscles under glucose-ingested and insulin-secreted conditions during hypoxia exposure (16% O2) after training. While no change in body composition was found in the control group, subjects who trained at altitude had unequivocally decreased fat mass (-1.7 ± 0.3 kg, -11.4%) with increased lean mass (+0.8 ± 0.2 kg, +1.5%). Arterial oxygen saturation significantly decreased with increased plasma lactate during hypoxia recovery mimicking 2,300 meters at altitude (~93% versus ~97%). Intriguingly, hypoxia resulted in elevated muscle THC, and sympathetic nervous activities occurred in parallel with greater-percent oxygen saturation in both muscle groups. In conclusion, the present study provides evidence that increased blood distribution to the skeletal muscle under postprandial condition may contribute to the reciprocally increased muscle mass and decreased body mass after a 3-week altitude exposure in swimmers.

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

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I. K. Hals

2013-01-01

Full Text Available Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8±3.5% in encapsulated and 42.9±5.2% in nonencapsulated islets (P<0.2. Nonencapsulated islets released 37.7% (median more HMGB1 compared to encapsulated islets after hypoxic culture conditions (P<0.001. Glucose-induced insulin release was marginally affected by hypoxia. Basal oxygen consumption was equally reduced in encapsulated and nonencapsulated islets, by 22.0±6.1% versus 24.8±5.7%. Among 27 tested cytokines/chemokines, hypoxia increased the secretion of IL-6 and IL-8/CXCL8 in both groups of islets, whereas an increase of MCP-1/CCL2 was seen only with nonencapsulated islets. Conclusion. Alginate microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation.

Hypoxia: From Placental Development to Fetal Programming.

Science.gov (United States)

Fajersztajn, Lais; Veras, Mariana Matera

2017-10-16

Hypoxia may influence normal and different pathological processes. Low oxygenation activates a variety of responses, many of them regulated by hypoxia-inducible factor 1 complex, which is mostly involved in cellular control of O 2 consumption and delivery, inhibition of growth and development, and promotion of anaerobic metabolism. Hypoxia plays a significant physiological role in fetal development; it is involved in different embryonic processes, for example, placentation, angiogenesis, and hematopoiesis. More recently, fetal hypoxia has been associated directly or indirectly with fetal programming of heart, brain, and kidney function and metabolism in adulthood. In this review, the role of hypoxia in fetal development, placentation, and fetal programming is summarized. Hypoxia is a basic mechanism involved in different pregnancy disorders and fetal health developmental complications. Although there are scientific data showing that hypoxia mediates changes in the growth trajectory of the fetus, modulates gene expression by epigenetic mechanisms, and determines the health status later in adulthood, more mechanistic studies are needed. Furthermore, if we consider that intrauterine hypoxia is not a rare event, and can be a consequence of unavoidable exposures to air pollution, nutritional deficiencies, obesity, and other very common conditions (drug addiction and stress), the health of future generations may be damaged and the incidence of some diseases will markedly increase as a consequence of disturbed fetal programming. Birth Defects Research 109:1377-1385, 2017.© 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Induction of adipocyte-like phenotype in human mesenchymal stem cells by hypoxia

DEFF Research Database (Denmark)

Fink, Trine; Abildtrup, Lisbeth Ann; Fogd, Kirsten

2004-01-01

Human mesenchymal stem cells (hMSCs) have the capacity to differentiate along several pathways to form bone, cartilage, tendon, muscle, and adipose tissues. The adult hMSCs reside in vivo in the bone marrow in niches where oxygen concentration is far below the ambient air, which is the most...... commonly encountered laboratory condition. The study reported here was designed to determine whether oxygen has a role in the differentiation of hMSCs into adipocytes. Indeed, when exposed to atmosphere containing only 1% of oxygen, the formation of adipocyte-like phenotype with cytoplasmic lipid....... High level of induction, however, was observed with the PPAR-gamma-induced angiopoietin-related gene, PGAR. The lack of an adipocyte-specific transcription pattern thus indicates that despite accumulation of the lipid, true adipogenic differentiation did not take place. In conclusion, hypoxia appears...

Cycling hypoxia: A key feature of the tumor microenvironment.

Science.gov (United States)

Michiels, Carine; Tellier, Céline; Feron, Olivier

2016-08-01

A compelling body of evidence indicates that most human solid tumors contain hypoxic areas. Hypoxia is the consequence not only of the chaotic proliferation of cancer cells that places them at distance from the nearest capillary but also of the abnormal structure of the new vasculature network resulting in transient blood flow. Hence two types of hypoxia are observed in tumors: chronic and cycling (intermittent) hypoxia. Most of the current work aims at understanding the role of chronic hypoxia in tumor growth, response to treatment and metastasis. Only recently, cycling hypoxia, with spatial and temporal fluctuations in oxygen levels, has emerged as another key feature of the tumor environment that triggers different responses in comparison to chronic hypoxia. Either type of hypoxia is associated with distinct effects not only in cancer cells but also in stromal cells. In particular, cycling hypoxia has been demonstrated to favor, to a higher extent than chronic hypoxia, angiogenesis, resistance to anti-cancer treatments, intratumoral inflammation and tumor metastasis. These review details these effects as well as the signaling pathway it triggers to switch on specific transcriptomic programs. Understanding the signaling pathways through which cycling hypoxia induces these processes that support the development of an aggressive cancer could convey to the emergence of promising new cancer treatments. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of Nanosize Zeolite Molecular Sieves for Medical Oxygen Concentration

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Mingfei Pan

2017-07-01

Full Text Available The development of a portable oxygen concentrator is of prime significance for patients with respiratory problems. This paper presents a portable concentrator prototype design using the pressure/vacuum swing adsorption (PVSA cycle with a deep evacuation step (−0.82 barg instead of desorption with purge flow to simplify the oxygen production process. The output of the oxygen concentrator is a ~90 vol % enriched oxygen stream in a continuous adsorption and desorption cycle (cycle time ~90 s. The size of the adsorption column is 3 cm in diameter and 20 cm in length. A Li+ exchanged 13X nanosize zeolite is used as the adsorbent to selectively adsorb nitrogen from air. A dynamic model of the pressure and vacuum swing adsorption units was developed to study the pressurization and depressurization process inside the microporous area of nanosized zeolites. The describing equations were solved using COMSOL Multiphysics Chemical Engineering module. The output flow rate and oxygen concentration results from the simulation model were compared with the experimental data. Velocity and concentration profiles were obtained to study the adsorption process and optimize the operational parameters.

Hypoxia enhances proliferation and tissue formation of human mesenchymal stem cells

International Nuclear Information System (INIS)

Grayson, Warren L.; Zhao, Feng; Bunnell, Bruce; Ma, Teng

2007-01-01

Changes in oxygen concentrations affect many of the innate characteristics of stem and progenitor cells. Human mesenchymal stem cells (hMSCs) were maintained under hypoxic atmospheres (2% O 2 ) for up to seven in vitro passages. This resulted in approximately 30-fold higher hMSC expansion over 6 weeks without loss of multi-lineage differentiation capabilities. Under hypoxia, hMSCs maintained their growth-rates even after reaching confluence, resulting in the formation of multiple cell layers. Hypoxic hMSCs also displayed differences in the cell and nuclear morphologies as well as enhanced ECM formation and organization. These changes in cellular characteristics were accompanied by higher mRNA levels of Oct-4 and HIF-2α, as well as increased expression levels of connexin-43, a protein used in gap junction formation. The results from this study demonstrated that oxygen concentrations affected many aspects of stem-cell physiology, including growth and in vitro development, and may be a critical parameter during expansion and differentiation

Hypoxia regulates microRNA expression in the human carotid body

International Nuclear Information System (INIS)

Mkrtchian, Souren; Lee, Kian Leong; Kåhlin, Jessica; Ebberyd, Anette; Poellinger, Lorenz; Fagerlund, Malin Jonsson; Eriksson, Lars I.

2017-01-01

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

Hypoxia regulates microRNA expression in the human carotid body

Energy Technology Data Exchange (ETDEWEB)

Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Lee, Kian Leong, E-mail: csilkl@nus.edu.sg [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Kåhlin, Jessica [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Ebberyd, Anette [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Poellinger, Lorenz [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Fagerlund, Malin Jonsson; Eriksson, Lars I. [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden)

2017-03-15

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

Use of an oxygen concentrator in a Nigerian neonatal unit: economic implications and reliability.

Science.gov (United States)

Mokuolu, Olugbenga A; Ajayi, Oluade A

2002-09-01

A 3-year experience of using an oxygen concentrator in a Nigerian newborn unit and economic appraisal of its effectiveness is reported. The oxygen concentrator is a device that absorbs nitrogen from ambient air, with a resultant oxygen concentration of 85 to 95% at different flow rates. The oxygen concentrator met our oxygen needs which averaged 18 hours a day, and had a huge cost advantage over the oxygen cylinders. The cost of oxygen via cylinder for just one patient for a year exceeds the initial capital outlay for a concentrator. The Puritan-Bennett oxygen concentrator has a lifespan of at least 7 years and is virtually maintenance-free for the 1st 26,400 hours of use, after which some major components might need replacement. We conclude that in developing countries oxygen concentrators are a more cost-effective, reliable and convenient means of oxygen supply than oxygen cylinders, and recommend their use where there is a high demand for oxygen.

Detrimental effects of hypoxia-specific expression of uracil DNA glycosylase (Ung) in Mycobacterium smegmatis.

Science.gov (United States)

Kurthkoti, Krishna; Varshney, Umesh

2010-12-01

Mycobacterium tuberculosis is known to reside latently in a significant fraction of the human population. Although the bacterium possesses an aerobic mode of metabolism, it adapts to persistence under hypoxic conditions such as those encountered in granulomas. While in mammalian systems hypoxia is a recognized DNA-damaging stress, aspects of DNA repair in mycobacteria under such conditions have not been studied. We subjected Mycobacterium smegmatis, a model organism, to the Wayne's protocol of hypoxia. Analysis of the mRNA of a key DNA repair enzyme, uracil DNA glycosylase (Ung), by real-time reverse transcriptase PCR (RT-PCR) revealed its downregulation during hypoxia. However, within an hour of recovery of the culture under normal oxygen levels, the Ung mRNA was restored. Analysis of Ung by immunoblotting and enzyme assays supported the RNA analysis results. To understand its physiological significance, we misexpressed Ung in M. smegmatis by using a hypoxia-responsive promoter of narK2 from M. tuberculosis. Although the misexpression of Ung during hypoxia decreased C-to-T mutations, it compromised bacterial survival upon recovery at normal oxygen levels. RT-PCR analysis of other base excision repair gene transcripts (UdgB and Fpg) suggested that these DNA repair functions also share with Ung the phenomenon of downregulation during hypoxia and recovery with return to normal oxygen conditions. We discuss the potential utility of this phenomenon in developing attenuated strains of mycobacteria.

Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

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Kumar Anil

2010-10-01

Full Text Available Abstract Background The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6 plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. Results We have shown that RGCs exposed to hypoxia (1% or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM, revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Conclusion Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.

Moderate hypoxia influences potassium outward currents in adipose-derived stem cells.

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Mayuri Prasad

Full Text Available Moderate hypoxic preconditioning of adipose-derived stem cells (ASCs enhances properties such as proliferation and secretion of growth factors, representing a valuable strategy to increase the efficiency of cell-based therapies. In a wide variety of cells potassium (K+ channels are key elements involved in the cellular responses to hypoxia, suggesting that ASCs cultured under low oxygen conditions may display altered electrophysiological properties. Here, the effects of moderate hypoxic culture on proliferation, whole-cell currents, and ion channel expression were investigated using human ASCs cultured at 5% and 20% oxygen. Although cell proliferation was greatly enhanced, the dose-dependent growth inhibition by the K+ channel blocker tetraethylammonium (TEA was not significantly affected by hypoxia. Under both normoxic and hypoxic conditions, ASCs displayed outward K+ currents composed by Ca2+-activated, delayed rectifier, and transient components. Hypoxic culture reduced the slope of the current-voltage curves and caused a negative shift in the voltage activation threshold of the whole-cell currents. However, the TEA-mediated shift of voltage activation threshold was not affected by hypoxia. Semiquantitative real-time RT-PCR revealed that expression of genes encoding for various ion channels subunits related to oxygen sensing and proliferation remained unchanged after hypoxic culture. In conclusion, outward currents are influenced by moderate hypoxia in ASCs through a mechanism that is not likely the result of modulation of TEA-sensitive K+ channels.

Cytoprotective effects of atmospheric-pressure plasmas against hypoxia-induced neuronal injuries

Science.gov (United States)

Yan, Xu; Meng, Zhaozhong; Ouyang, Jiting; Qiao, Yajun; Li, Jiaxin; Jia, Mei; Yuan, Fang; (Ken Ostrikov, Kostya

2018-02-01

Atmospheric pressure plasma jet (APPJ) has recently been the focus of cytoprotective research due to the physiological roles of ROS and RNS. In the current study, we investigated the effect of APPJ treatment on the hypoxia (1% oxygen) induced cell injuries. SH-SY5Y cells were treated by APPJ for different duration and incubated in normoxic condition (20% oxygen) for 5 h followed by 24 h hypoxia treatment. Cell viability was evaluated by lactate dehydrogenase (LDH) release and further monitored using the electric cell-substrate impedance sensing (ECIS) system after APPJ treatment. Results showed that APPJ could reduce cell injuries after 24 h hypoxia, which was consistent with the ECIS results. Furthermore, extracellular NO and H2O2 production was significantly increased with the APPJ treatment. It was also interesting to find that APPJ treatment reduced SH-SY5Y cells proliferation in the hypoxic microenvironment during the first 20 h of hypoxia. Although more work was still need to clarify whether the cell viability maintenance was related to the cell proliferation during hypoxia, our results provide the first evidence of real-time cell viability changes after APPJ treatment under both normoxic and hypoxic conditions, which could provide evidence for the neuroprotective applications of APPJ.

The role of hypoxia-induced factor in the regulation of oxygen homeostasis during reparative regeneration in compromised microcirculation

Directory of Open Access Journals (Sweden)

S. G. Izmaylov

2017-01-01

Full Text Available The aim of the present review is to find an answer to the clinically important question on the mechanisms regulating the activity of reparative regeneration in hypoxic conditions and potential ways to modify this process. In the recent studies, compensated hypoxia is characterized as a trigger for the regeneration, with the central regulating factor being the member of the cytokine family, hypoxia-inducible factor-1 (HIF-1. Changes in the concentration of this protein modulates cell migration, angiogenesis and epithelialmesenchymal integration; it also stimulates the proliferation of endothelial cells and fibroblasts, playing a  major role in the stimulation of wound healing, especially with compromised microcirculation, for example, diabetes mellitus. 

Evaluation of the Oxygen Concentrator Prototypes: Pressure Swing Adsorption Prototype and Electrochemical Prototype

Science.gov (United States)

Gilkey, Kelly M.; Olson, Sandra L.

2015-01-01

An oxygen concentrator is needed to provide enriched oxygen in support of medical contingency operations for future exploration human spaceflight programs. It would provide continuous oxygen to an ill or injured crew member in a closed cabin environment. Oxygen concentration technology is being pursued to concentrate oxygen from the ambient environment so oxygen as a consumable resource can be reduced. Because oxygen is a critical resource in manned spaceflight, using an oxygen concentrator to pull oxygen out of the ambient environment instead of using compressed oxygen can provide better optimization of resources. The overall goal of this project is to develop an oxygen concentrator module that minimizes the hardware mass, volume, and power footprint while still performing at the required clinical capabilities. Should a medical event occur that requires patient oxygenation, the release of 100 percent oxygen into a small closed cabin environment can rapidly raise oxygen levels to the vehicles fire limit. The use of an oxygen concentrator to enrich oxygen from the ambient air and concentrate it to the point where it can be used for medical purposes means no oxygen is needed from the ultra-high purity (99.5+% O2) oxygen reserve tanks. By not adding oxygen from compressed tanks to the cabin environment, oxygen levels can be kept below the vehicle fire limit thereby extending the duration of care provided to an oxygenated patient without environmental control system intervention to keep the cabin oxygen levels below the fire limits. The oxygen concentrator will be a Food and Drug Administration (FDA) clearable device. A demonstration unit for the International Space Station (ISS) is planned to verify the technology and provide oxygen capability. For the ISS, the demonstration unit should not exceed 10 kg (approximately 22 lb), which is the soft stowage mass limit for launch on resupply vehicles for the ISS. The unit's size should allow for transport within the

Hypoxia, Color Vision Deficiencies, and Blood Oxygen Saturation

Science.gov (United States)

2013-11-01

using the Dvorine Pseudoisochromatic Plate Test (2nd edition, Psychological Corporation, Baltimore, MD) illuminated by True Daylight Illuminator T8...Plant, G.T. (1994). Insights into the different exploits of colour in the visual cortex. Proc Biol Sci, 258 (1353), 327-334. Barbur, J.L...Aviat Space Environ Med, 80, 933-940. Crow, T.J.,& Kelman, G.R.(1973). Psychological effects of mild acute hypoxia. Br J Anaesth, 45, 335-337

PRONOUNCED MUSCLE DEOXYGENATION DURING SUPRAMAXIMAL EXERCISE UNDER SIMULATED HYPOXIA IN SPRINT ATHLETES

Directory of Open Access Journals (Sweden)

Kazuo Oguri

2008-12-01

Full Text Available The purpose of this study was to determine whether acute hypoxia alters the deoxygenation level in vastus lateralis muscle during a 30 s Wingate test, and to compare the muscle deoxygenation level between sprint athletes and untrained men. Nine male track sprinters (athletic group, VO2max 62.5 ± 4.1 ml/kg/min and 9 healthy untrained men (untrained group, VO2max 49.9 ± 5.2 ml·kg-1·min-1 performed a 30 s Wingate test under simulated hypoxic (FIO2 = 0.164 and PIO2 = 114 mmHg and normoxic conditions. During the exercise, changes in oxygenated hemoglobin (OxyHb in the vastus lateralis were measured using near infrared continuous wave spectroscopy. Decline in OxyHb, that is muscle deoxygenation, was expressed as percent change from baseline. Percutaneous arterial oxygen saturation (SpO2, oxygen uptake (VO2, and ventilation (VE were measured continuously. In both groups, there was significantly greater muscle deoxygenation, lower SpO2, lower peakVO2, and higher peakVE during supramaximal exercise under hypoxia than under normoxia, but no differences in peak and mean power output during the exercise. Under hypoxia, the athletic group experienced significantly greater muscle deoxygenation, lower SpO2, greater decrement in peakVO2 and increment in peakVE during the exercise than the untrained group. When the athletic and untrained groups were pooled, the increment of muscle deoxygenation was strongly correlated with lowest SpO2 in the 30 s Wingate test under hypoxia. These results suggest that acute exposure to hypoxia causes a greater degree of peripheral muscle deoxygenation during supramaximal exercise, especially in sprint athletes, and this physiological response would be explained mainly by lower arterial oxygen saturation

Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia.

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Michael Berney

Full Text Available Mycobacteria are a group of obligate aerobes that require oxygen for growth, but paradoxically have the ability to survive and metabolize under hypoxia. The mechanisms responsible for this metabolic plasticity are unknown. Here, we report on the adaptation of Mycobacterium smegmatis to slow growth rate and hypoxia using carbon-limited continuous culture. When M. smegmatis is switched from a 4.6 h to a 69 h doubling time at a constant oxygen saturation of 50%, the cells respond through the down regulation of respiratory chain components and the F1Fo-ATP synthase, consistent with the cells lower demand for energy at a reduced growth rate. This was paralleled by an up regulation of molecular machinery that allowed more efficient energy generation (i.e. Complex I and the use of alternative electron donors (e.g. hydrogenases and primary dehydrogenases to maintain the flow of reducing equivalents to the electron transport chain during conditions of severe energy limitation. A hydrogenase mutant showed a 40% reduction in growth yield highlighting the importance of this enzyme in adaptation to low energy supply. Slow growing cells at 50% oxygen saturation subjected to hypoxia (0.6% oxygen saturation responded by switching on oxygen scavenging cytochrome bd, proton-translocating cytochrome bc1-aa3 supercomplex, another putative hydrogenase, and by substituting NAD+-dependent enzymes with ferredoxin-dependent enzymes thus highlighting a new pattern of mycobacterial adaptation to hypoxia. The expression of ferredoxins and a hydrogenase provides a potential conduit for disposing of and transferring electrons in the absence of exogenous electron acceptors. The use of ferredoxin-dependent enzymes would allow the cell to maintain a high carbon flux through its central carbon metabolism independent of the NAD+/NADH ratio. These data demonstrate the remarkable metabolic plasticity of the mycobacterial cell and provide a new framework for understanding their

The effect of hypobaric hypoxia on multichannel EEG signal complexity.

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Papadelis, Christos; Kourtidou-Papadeli, Chrysoula; Bamidis, Panagiotis D; Maglaveras, Nikos; Pappas, Konstantinos

2007-01-01

The objective of this study was the development and evaluation of nonlinear electroencephalography parameters which assess hypoxia-induced EEG alterations, and describe the temporal characteristics of different hypoxic levels' residual effect upon the brain electrical activity. Multichannel EEG, pO2, pCO2, ECG, and respiration measurements were recorded from 10 subjects exposed to three experimental conditions (100% oxygen, hypoxia, recovery) at three-levels of reduced barometric pressure. The mean spectral power of EEG under each session and altitude were estimated for the standard bands. Approximate Entropy (ApEn) of EEG segments was calculated, and the ApEn's time-courses were smoothed by a moving average filter. On the smoothed diagrams, parameters were defined. A significant increase in total power and power of theta and alpha bands was observed during hypoxia. Visual interpretation of ApEn time-courses revealed a characteristic pattern (decreasing during hypoxia and recovering after oxygen re-administration). The introduced qEEG parameters S1 and K1 distinguished successfully the three hypoxic conditions. The introduced parameters based on ApEn time-courses are assessing reliably and effectively the different hypoxic levels. ApEn decrease may be explained by neurons' functional isolation due to hypoxia since decreased complexity corresponds to greater autonomy of components, although this interpretation should be further supported by electrocorticographic animal studies. The introduced qEEG parameters seem to be appropriate for assessing the hypoxia-related neurophysiological state of patients in the hyperbaric chambers in the treatment of decompression sickness, carbon dioxide poisoning, and mountaineering.

Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia.

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Hals, Ingrid K; Bruerberg, Simon Gustafson; Ma, Zuheng; Scholz, Hanne; Björklund, Anneli; Grill, Valdemar

2015-01-01

To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20-22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets

Effects of ambient oxygen concentration on soot temperature and concentration for biodiesel and diesel spray combustion

KAUST Repository

Zhang, Ji

2015-06-01

Ambient oxygen concentration, a key variable directly related to exhaust gas recirculation (EGR) levels in diesel engines, plays a significant role in particulate matter (PM) and nitrogen oxides (NOx) emissions. The utilization of biodiesel in diesel engines has been investigated over the last decades for its renewable characteristics and lower emissions compared to diesel. In an earlier work, we demonstrated that the soot temperature and concentration of biodiesel were lower than diesel under regular diesel engine conditions without EGR. Soot concentration was quantified by a parameter called KL factor. As a continuous effort, this paper presents an experimental investigation of the ambient oxygen concentration on soot temperature and KL factor during biodiesel and diesel spray combustion. The experiment was implemented in a constant volume chamber system, where the ambient oxygen concentration varied from 21 to 10% and the ambient temperature was kept to 1,000 K. A high speed two-color pyrometry technique was used to measure transient soot temperature and the KL factor of the spray flame. The soot temperature of biodiesel is found to be lower than that of diesel under the same conditions, which follows the same trend from our previous results found when the ambient temperature changes to 21% oxygen conditions. A reduction in ambient oxygen concentration generally reduces the soot temperature for both fuels. However, this is a complicated effect on soot processes as the change of oxygen concentration greatly affects the balance between soot formation and oxidation. The KL factor is observed to be the highest at 12% O2 for diesel and 18% O2 for biodiesel, respectively. On the other hand, the 10% O2 condition shows the lowest KL factor for both fuels. These results can provide quantitative experimental evidences to optimize the ambient oxygen concentration for diesel engines using different fuels for better emissions characteristics. © 2014 American Society of

Placental Gas Exchange and the Oxygen Supply to the Fetus

DEFF Research Database (Denmark)

Carter, Anthony M

2015-01-01

The oxygen supply of the fetus depends on the blood oxygen content and flow rate in the uterine and umbilical arteries and the diffusing capacity of the placenta. Oxygen consumption by the placenta is a significant factor and a potential limitation on availability to the fetus. The relevance...... anaerobic conditions and even the fetus is adapted to a low oxygen environment. Nevertheless, there is a reserve capacity, and during acute hypoxia the fetus can counter a 50% reduction in oxygen delivery by increasing fractional extraction. During sustained hypoxia, on the other hand, fetal growth...

Effect of hypoxia on benthic nutrient fluxes in the northwestern Black Sea

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Friedrich, J.

2012-04-01

The western Black Sea shelf has been affected by eutrophication from the 1960s to the mid 1990s. A combination of increased nutrient loads from the major inflowing rivers Danube, Dniester and Dnepr and favourable climate conditions led to high productivity regimes. As a consequence, increased oxygen consumption due to decomposition of organic matter caused recurrent seasonal bottom water hypoxia for more than 20 years. In addition, recycling of nutrients from organic matter settling to the seafloor along with tight benthic-pelagic coupling represents an important internal source for productivity, hence internally supporting eutrophication. From the 1970s to 1990s, the benthic and pelagic systems deteriorated and ecosystem structure and functioning changed. Following the collapse of the centrally planned economies in the eastern European countries during the 1990s, the riverine nutrient input decreased, and the ecosystem, now slowly responding, shows signs of recovery; e.g. by a decrease in hypoxic events. In this study, benthic nutrient flux data from in-situ and ex-situ experiments during the 1990s on the Danube-influenced north-western Black Sea shelf and data from the 2000s, including the EU-FP7 HYPOX experiments, are analysed to reveal the effect of hypoxia on benthic nutrient fluxes. Mann-Whitney statistical tests have been applied to demonstrate the significance of differences in fluxes due to varying oxygen conditions in the water. During the 1990s experiments, bottom water hypoxia was encountered in all locations, while during the 2000s hypoxia has been met only during summer in the Danube Prodelta area and near the Dniester mouth. Indeed, bottom water oxygen in the 1990s has been statistically significantly lower than in the 2000s while benthic oxygen consumption was higher during eutrophication-induced hypoxia. The benthic nutrient fluxes in the 1990s and the 2000s however do not differ significantly. During hypoxia, despite ceasing eutrophication

Effect of hyperbaric oxygen therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents

DEFF Research Database (Denmark)

Lawson-Smith, Pia; Jansen, Erik C; Hilsted, Linda

2010-01-01

Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction...... and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure...

Hypoxia and anoxia effects on alcohol dehydrogenase activity and hemoglobin content in Chironomus riparius Meigen, 1804

Directory of Open Access Journals (Sweden)

Valentina Grazioli

2016-02-01

Full Text Available The metabolic effects of low oxygen content on alcohol-dehydrogenase (ADH activity and hemoglobin (Hb concentration were investigated in IV-instar larvae of Chironomus riparius (Diptera: Chironomidae from an Italian stream. Two series of short-term (48 h experiments were carried out: exposure to (1 progressive hypoxia (95 to 5% of oxygen saturation and (2 anoxia (at <5% of oxygen saturation. In (1, Hb amount increased with increasing oxygen depletion up to a critical value of oxygenation (about 70% of oxygen saturation. Below this percentage, the Hb amount declined to values comparable with those present in the control. The respiration rate (R remained almost constant at oxygen saturation >50% and decreased significantly only after 48 h of treatment (= <5% of oxygen saturation reaching values <100 mmolO2 gAFDW-1 h-1. ADH activity showed two phases of growth, within the first 14 h and over 18 h of exposure. Overall, we inferred that i Hb might function as short-term oxygen storage, enabling animals to delay the on-set of anaerobiosis; and ii alcoholic fermentation co-occurs for a short time with aerobic respiration, becoming the prevalent metabolic pathway below 5% of oxygen saturation (<1 mg L-1. These considerations were supported also by results from anoxia exposure (2. In such condition, larvae were visibly stressed, becoming immobile after few minutes of incubation, and ADH reached higher values than in the hypoxia treatment (2.03±0.15 UADH mg prot-1. Overall, this study showed a shift from aerobic to anaerobic activity in C. riparius larvae exposed to poorly oxygenated water with an associated alteration of ADH activity and the Hb amount. Such metabolites might be valid candidate biomarkers for the environmental monitoring of running waters.

Effects of simulated altitude (normobaric hypoxia on cardiorespiratory parameters and circulating endothelial precursors in healthy subjects

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Pierini Alberto

2007-08-01

Full Text Available Abstract Background Circulating Endothelial Precursors (PB-EPCs are involved in the maintenance of the endothelial compartment being promptly mobilized after injuries of the vascular endothelium, but the effects of a brief normobaric hypoxia on PB-EPCs in healthy subjects are scarcely studied. Methods Clinical and molecular parameters were investigated in healthy subjects (n = 8 in basal conditions (T0 and after 1 h of normobaric hypoxia (T1, with Inspiratory Fraction of Oxygen set at 11.2% simulating 4850 mt of altitude. Blood samples were obtained at T0 and T1, as well as 7 days after hypoxia (T2. Results In all studied subjects we observed a prompt and significant increase in PB-EPCs, with a return to basal value at T2. The induction of hypoxia was confirmed by Alveolar Oxygen Partial Pressure (PAO2 and Spot Oxygen Saturation decreases. Heart rate increased, but arterial pressure and respiratory response were unaffected. The change in PB-EPCs percent from T0 to T1 was inversely related to PAO2 at T1. Rapid (T1 increases in serum levels of hepatocyte growth factor and erythropoietin, as well as in cellular PB-EPCs-expression of Hypoxia Inducible Factor-1α were observed. Conclusion In conclusion, the endothelial compartment seems quite responsive to standardized brief hypoxia, possibly important for PB-EPCs activation and recruitment.

2013 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2011 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2008 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2009 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2015 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2012 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

2010 Summer Hypoxia Watch Bottom CTD Station Locations

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA Hypoxia Watch project provides near-real-time, web-based maps of dissolved oxygen near the sea floor over the Texas-Louisiana continental shelf during a...

Hypoxia-Inducible Factor 1 Is an Inductor of Transcription Factor Activating Protein 2 Epsilon Expression during Chondrogenic Differentiation

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Stephan Niebler

2015-01-01

Full Text Available The transcription factor AP-2ε (activating enhancer-binding protein epsilon is expressed in cartilage of humans and mice. However, knowledge about regulatory mechanisms influencing AP-2ε expression is limited. Using quantitative real time PCR, we detected a significant increase in AP-2ε mRNA expression comparing initial and late stages of chondrogenic differentiation processes in vitro and in vivo. Interestingly, in these samples the expression pattern of the prominent hypoxia marker gene angiopoietin-like 4 (Angptl4 strongly correlated with that of AP-2ε suggesting that hypoxia might represent an external regulator of AP-2ε expression in mammals. In order to show this, experiments directly targeting the activity of hypoxia-inducible factor-1 (HIF1, the complex mediating responses to oxygen deprivation, were performed. While the HIF1-activating compounds 2,2′-dipyridyl and desferrioxamine resulted in significantly enhanced mRNA concentration of AP-2ε, siRNA against HIF1α led to a significantly reduced expression rate of AP-2ε. Additionally, we detected a significant upregulation of the AP-2ε mRNA level after oxygen deprivation. In sum, these different experimental approaches revealed a novel role for the HIF1 complex in the regulation of the AP-2ε gene in cartilaginous cells and underlined the important role of hypoxia as an important external regulatory stimulus during chondrogenic differentiation modulating the expression of downstream transcription factors.

Nutritional status in chronic obstructive pulmonary disease: role of hypoxia.

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Raguso, Comasia A; Luthy, Christophe

2011-02-01

In patients with chronic obstructive pulmonary disease (COPD), malnutrition and limited physical activity are very common and contribute to disease prognosis, whereas a balance between caloric intake and exercise allows body weight stability and muscle mass preservation. The goal of this review is to analyze the implications of chronic hypoxia on three key elements involved in energy homeostasis and its role in COPD cachexia. The first one is energy intake. Body weight loss, often observed in patients with COPD, is related to lack of appetite. Inflammatory cytokines are known to be involved in anorexia and to be correlated to arterial partial pressure of oxygen. Recent studies in animals have investigated the role of hypoxia in peptides involved in food consumption such as leptin, ghrelin, and adenosine monophosphate activated protein kinase. The second element is muscle function, which is strongly related to energy use. In COPD, muscle atrophy and muscle fiber shift to the glycolytic type might be an adaptation to chronic hypoxia to preserve the muscle from oxidative stress. Muscle atrophy could be the result of a marked activation of the ubiquitin-proteasome pathway as found in muscle of patients with COPD. Hypoxia, via hypoxia inducible factor-1, is implicated in mitochondrial biogenesis and autophagy. Third, hormonal control of energy balance seems to be affected in patients with COPD. Insulin resistance has been described in this group of patients as well as a sort of "growth hormone resistance." Hypoxia, by hypoxia inducible factor-1, accelerates the degradation of tri-iodothyronine and thyroxine, decreasing cellular oxygen consumption, suggesting an adaptive mechanism rather than a primary cause of COPD cachexia. COPD rehabilitation aimed at maintaining function and quality of life needs to address body weight stabilization and, in particular, muscle mass preservation. Copyright © 2011 Elsevier Inc. All rights reserved.

Susceptibility to hypoxia and breathing control changes after short-term cold exposures

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Lyudmila T. Kovtun

2013-08-01

Full Text Available Background . Hypoxia is the reduction of oxygen availability due to external or internal causes. There is large individual variability of response to hypoxia. Objective . The aim of this study was to define individual and typological features in susceptibility to hypoxia, its interrelation with hypoxic and hypercapnic ventilatory responses (HVR and HCVR, respectively and their changes after cold acclimation. Design . Twenty-four healthy men were tested. HVR and HCVR were measured by the rebreathing method during hypoxic and hypercapnic tests, respectively. These tests were carried out in thermoneutral conditions before and after cold exposures (nude, at 13°C, 2 h daily, for 10 days. Susceptibility to hypoxia (sSaO2 was determined as haemoglobin saturation slope during hypoxic test. Results . It was found that HVR and HCVR significantly increased and susceptibility to hypoxia (sSaO2 tended to decrease after cold acclimation. According to sSaO2 results before cold exposures, the group was divided into 3: Group 1 – with high susceptibility to hypoxia, Group 2 – medium and Group 3 – low susceptibility. Analysis of variances (MANOVA shows the key role of susceptibility to hypoxia and cold exposures and their interrelation. Posterior analysis (Fisher LSD showed significant difference in susceptibility to hypoxia between the groups prior to cold acclimation, while HVR and HCVR did not differ between the groups. After cold acclimation, susceptibility to hypoxia was not significantly different between the groups, while HCVR significantly increased in Groups 1 and 3, HVR significantly increased in Group 3 and HCVR, HVR did not change in Group 2. Conclusions . Short-term cold exposures caused an increase in functional reserves and improved oxygen supply of tissues in Group 1. Cold exposure hypoxia has caused energy loss in Group 3. Group 2 showed the most appropriate energy conservation reaction mode to cold exposures. No relation was found between

Determination of the Minimal Fresh Gas Flow to Maintain a Therapeutic Inspired Oxygen Concentration in a Semi-Closed Anesthesia Circle System Using an Oxygen Concentrator as the Oxygen Source

National Research Council Canada - National Science Library

Grano, Joan

2001-01-01

The purpose of this study was to determine the rate of oxygen dilution, resulting from argon accumulation, using 3 low fresh gas flow rates using an oxygen concentrator in a semi-closed anesthesia circle system...

Impact of hypoxia stress on the physiological responses of sea cucumber Apostichopus japonicus: respiration, digestion, immunity and oxidative damage

Directory of Open Access Journals (Sweden)

Da Huo

2018-04-01

Full Text Available Hypoxia is one of the most frequently occurring stressors confronted by industrial cultures of sea cucumber and can cause large economic losses and resource degradation. However, its responsive mechanisms are still lacking. In this paper, the physiological responses of Apostichopus japonicus to oxygen deficiency was illustrated, including induced oxidative response and immune defense and changed digestive enzymes activities. Significantly increased activities of alpha-amylase (AMS, acid phosphatase (ACP, lactate dehydrogenase, catalase, peroxidase, succinate dehydrogenase and higher content of malondialdehyde, and decreased activities of lipase and trypsin (TRY were observed after hypoxia exposure (dissolved oxygen [DO] 2 mg/L. Expressions of key genes showed that AMS, peptidase, ACP, alkaline phosphatase, lysozyme, heat shock protein 70 and glutathione peroxidase were increased and TRY was decreased under hypoxia. With the decline of the DO level, the decreased tendency of oxygen consumption rates was different in varied weight groups. Moreover, respiratory trees were observed degraded under long-term hypoxia stress, thus leading a negative effect of respiration. These results could help to develop a better understanding of the responsive mechanism of sea cucumber under hypoxia stress and provide a theoretical basis for the prevention of hypoxia risk.

Approximate Simulation of Acute Hypobaric Hypoxia with Normobaric Hypoxia

Science.gov (United States)

Conkin, J.; Wessel, J. H., III

2011-01-01

INTRODUCTION. Some manufacturers of reduced oxygen (O2) breathing devices claim a comparable hypobaric hypoxia (HH) training experience by providing F(sub I) O2 pO2) of the target altitude. METHODS. Literature from investigators and manufacturers indicate that these devices may not properly account for the 47 mmHg of water vapor partial pressure that reduces the inspired partial pressure of O2 (P(sub I) O2). Nor do they account for the complex reality of alveolar gas composition as defined by the Alveolar Gas Equation. In essence, by providing iso-pO2 conditions for normobaric hypoxia (NH) as for HH exposures the devices ignore P(sub A)O2 and P(sub A)CO2 as more direct agents to induce signs and symptoms of hypoxia during acute training exposures. RESULTS. There is not a sufficient integrated physiological understanding of the determinants of P(sub A)O2 and P(sub A)CO2 under acute NH and HH given the same hypoxic pO2 to claim a device that provides isohypoxia. Isohypoxia is defined as the same distribution of hypoxia signs and symptoms under any circumstances of equivalent hypoxic dose, and hypoxic pO2 is an incomplete hypoxic dose. Some devices that claim an equivalent HH experience under NH conditions significantly overestimate the HH condition, especially when simulating altitudes above 10,000 feet (3,048 m). CONCLUSIONS. At best, the claim should be that the devices provide an approximate HH experience since they only duplicate the ambient pO2 at sea level as at altitude (iso-pO2 machines). An approach to reduce the overestimation is to at least provide machines that create the same P(sub I)O2 (iso-P(sub I)O2 machines) conditions at sea level as at the target altitude, a simple software upgrade.

Macrophage-mediated response to hypoxia in disease

Directory of Open Access Journals (Sweden)

Tazzyman S

2014-11-01

Full Text Available Simon Tazzyman,1 Craig Murdoch,2 James Yeomans,1 Jack Harrison,1 Munitta Muthana3 1Department of Oncology, 2School of Clinical Dentistry, 3Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Hypoxia plays a critical role in the pathobiology of various inflamed, diseased tissues, including malignant tumors, atherosclerotic plaques, myocardial infarcts, the synovia of rheumatoid arthritic joints, healing wounds, and sites of bacterial infection. These areas of hypoxia form when the blood supply is occluded and/or the oxygen supply is unable to keep pace with cell growth and/or infiltration of inflammatory cells. Macrophages are ubiquitous in all tissues of the body and exhibit great plasticity, allowing them to perform divergent functions, including, among others, patrolling tissue, combating invading pathogens and tumor cells, orchestrating wound healing, and restoring homeostasis after an inflammatory response. The number of tissue macrophages increases markedly with the onset and progression of many pathological states, with many macrophages accumulating in avascular and necrotic areas, where they are exposed to hypoxia. Recent studies show that these highly versatile cells then respond rapidly to the hypoxia present by altering their expression of a wide array of genes. Here we review the evidence for hypoxia-driven macrophage inflammatory responses in various disease states, and how this influences disease progression and treatment. Keywords: macrophage, hypoxia, inflammation, cytokine

Sulfide-inhibition of mitochondrial respiration at very low oxygen concentrations.

Science.gov (United States)

Matallo, J; Vogt, J; McCook, O; Wachter, U; Tillmans, F; Groeger, M; Szabo, C; Georgieff, M; Radermacher, P; Calzia, E

2014-09-15

Our aim was to study the ability of an immortalized cell line (AMJ2-C11) to sustain aerobic cell respiration at decreasing oxygen concentrations under continuous sulfide exposure. We assumed that the rate of elimination of sulfide through the pathway linked to the mitochondrial respiratory chain and therefore operating under aerobic conditions, should decrease with limiting oxygen concentrations. Thus, sulfide's inhibition of cellular respiration would occur faster under continuous sulfide exposure when the oxygen concentration is in the very low range. The experiments were performed with an O2K-oxygraph (Oroboros Instruments) by suspending 0.5-1×10(6) cells in 2 ml of continuously stirred respiration medium at 37 °C and calculating the oxygen flux (JO2) as the negative derivative of the oxygen concentration in the medium. The cells were studied in two different metabolic states, namely under normal physiologic respiration (1) and after uncoupling of mitochondrial respiration (2). Oxygen concentration was controlled by means of a titration-injection pump, resulting in average concentration values of 0.73±0.05 μM, 3.1±0.2 μM, and 6.2±0.2 μM. Simultaneously we injected a 2 mM Na2S solution at a continuous rate of 10 μl/s in order to quantify the titration-time required to reduce the JO2 to 50% of the initial respiratory activity. Under the lowest oxygen concentration this effect was achieved after 3.5 [0.3;3.5] and 11.7 [6.2;21.2]min in the uncoupled and coupled state, respectively. This time was statistically significantly shorter when compared to the intermediate and the highest O2 concentrations tested, which yielded values of 24.6 [15.5;28.1]min (coupled) and 35.9 [27.4;59.2]min (uncoupled), as well as 42.4 [27.5;42.4]min (coupled) and 51.5 [46.4;51.7]min (uncoupled). All data are medians [25%, and 75% percentiles]. Our results confirm that the onset of inhibition of cell respiration by sulfide occurs earlier under a continuous exposure when approaching

Zooplankton Responses to Low-Oxygen Condition upon a Shallow Oxygen Minimum Zone in the Upwelling Region off Chile

Science.gov (United States)

Hidalgo, P.; Escribano, R.

2015-12-01

A shallow oxygen minimum zone (OMZ) is a critical component in the coastal upwelling ecosystem off Chile. This OMZ causes oxygen-deficient water entering the photic layer and affecting plankton communities having low tolerance to hypoxia. Variable, and usually species-dependent, responses of zooplankton to hypoxia condition can be found. Most dominant species avoid hypoxia by restricting their vertical distribution, while others can temporarily enter and even spent part of their life cycle within the OMZ. Whatever the case, low-oxygen conditions appear to affect virtually all vital rates of zooplankton, such as mortality, fecundity, development and growth and metabolism, and early developmental stages seem more sensitive, with significant consequences for population and community dynamics. For most study cases, these effects are negative at individual and population levels. Observations and predictions upon increasing upwelling intensity over the last 20-30 years indicate a gradual shoaling of the OMZ, and so that an expected enhancement of these negative effects of hypoxia on the zooplankton community. Unknown processes of adaptation and community-structure adjustments are expected to take place with uncertain consequences for the food web of this highly productive eastern boundary current ecosystem.

[Generation of Superoxide Radicals by Complex III in Heart Mitochondria and Antioxidant Effect of Dinitrosyl Iron Complexes at Different Partial Pressure of Oxygen].

Science.gov (United States)

Dudylina, A L; Ivanova, M V; Shumaev, K B; Ruuge, E K

2016-01-01

The EPR spin-trapping technique and EPR-oximetry were used to study generation of superoxide radicals in heart mitochondria isolated from Wistar rats under conditions of variable oxygen concentration. Lithium phthalocyanine and TEMPONE-15N-D16 were chosen to determine oxygen content in a gas-permeable capillary tube containing mitochondria. TIRON was used as a spin trap. We investigated the influence of different oxygen concentrations in incubation mixture and demonstrated that heart mitochondria can generate superoxide in complex III at different partial pressure of oxygen as well as under the conditions of deep hypoxia (partial pressure of oxygen, but the magnitude and kinetic characteristics of the effect depended on the concentration of the drug.

Relationship between oxygen concentration, respiration and filtration rate in blue mussel Mytilus edulis

Science.gov (United States)

Tang, Baojun; Riisgård, Hans Ulrik

2018-03-01

The large water-pumping and particle-capturing gills of the filter-feeding blue mussel Mytilus edulis are oversized for respiratory purposes. Consequently, the oxygen uptake rate of the mussel has been suggested to be rather insensitive to decreasing oxygen concentrations in the ambient water, since the diffusion rate of oxygen from water flowing through the mussel determines oxygen uptake. We tested this hypothesis by measuring the oxygen uptake in mussels exposed to various oxygen concentrations. These concentrations were established via N2-bubbling of the water in a respiration chamber with mussels fed algal cells to stimulate fully opening of the valves. It was found that mussels exposed to oxygen concentrations decreasing from 9 to 2 mg O2/L resulted in a slow but significant reduction in the respiration rate, while the filtration rate remained high and constant. Thus, a decrease of oxygen concentration by 78% only resulted in a 25% decrease in respiration rate. However, at oxygen concentrations below 2 mg O2/L M. edulis responded by gradually closing its valves, resulting in a rapid decrease of filtration rate, concurrent with a rapid reduction of respiration rate. These observations indicated that M. edulis is no longer able to maintain its normal aerobic metabolism at oxygen concentration below 2 mg O2/L, and there seems to be an energy-saving mechanism in bivalve molluscs to strongly reduce their activity when exposed to low oxygen conditions.

Characterization of positron emission tomography hypoxia tracer uptake and tissue oxygenation via electrochemical modeling

NARCIS (Netherlands)

Bowen, S.R.; Kogel, A.J. van der; Nordsmark, M.; Bentzen, S.M.; Jeraj, R.

2011-01-01

PURPOSE: Unique uptake and retention mechanisms of positron emission tomography (PET) hypoxia tracers make in vivo comparison between them challenging. Differences in imaged uptake of two common hypoxia radiotracers, [(61)Cu]Cu-ATSM and [(18)F]FMISO, were characterized via computational modeling to

Effects of hypoxia and ocean acidification on the upper thermal niche boundaries of coral reef fishes.

Science.gov (United States)

Ern, Rasmus; Johansen, Jacob L; Rummer, Jodie L; Esbaugh, Andrew J

2017-07-01

Rising ocean temperatures are predicted to cause a poleward shift in the distribution of marine fishes occupying the extent of latitudes tolerable within their thermal range boundaries. A prevailing theory suggests that the upper thermal limits of fishes are constrained by hypoxia and ocean acidification. However, some eurythermal fish species do not conform to this theory, and maintain their upper thermal limits in hypoxia. Here we determine if the same is true for stenothermal species. In three coral reef fish species we tested the effect of hypoxia on upper thermal limits, measured as critical thermal maximum (CT max ). In one of these species we also quantified the effect of hypoxia on oxygen supply capacity, measured as aerobic scope (AS). In this species we also tested the effect of elevated CO 2 (simulated ocean acidification) on the hypoxia sensitivity of CT max We found that CT max was unaffected by progressive hypoxia down to approximately 35 mmHg, despite a substantial hypoxia-induced reduction in AS. Below approximately 35 mmHg, CT max declined sharply with water oxygen tension ( P w O 2 ). Furthermore, the hypoxia sensitivity of CT max was unaffected by elevated CO 2 Our findings show that moderate hypoxia and ocean acidification do not constrain the upper thermal limits of these tropical, stenothermal fishes. © 2017 The Author(s).

The multi-level impact of chronic intermittent hypoxia on central auditory processing.

Science.gov (United States)

Wong, Eddie; Yang, Bin; Du, Lida; Ho, Wai Hong; Lau, Condon; Ke, Ya; Chan, Ying Shing; Yung, Wing Ho; Wu, Ed X

2017-08-01

During hypoxia, the tissues do not obtain adequate oxygen. Chronic hypoxia can lead to many health problems. A relatively common cause of chronic hypoxia is sleep apnea. Sleep apnea is a sleep breathing disorder that affects 3-7% of the population. During sleep, the patient's breathing starts and stops. This can lead to hypertension, attention deficits, and hearing disorders. In this study, we apply an established chronic intermittent hypoxemia (CIH) model of sleep apnea to study its impact on auditory processing. Adult rats were reared for seven days during sleeping hours in a gas chamber with oxygen level cycled between 10% and 21% (normal atmosphere) every 90s. During awake hours, the subjects were housed in standard conditions with normal atmosphere. CIH treatment significantly reduces arterial oxygen partial pressure and oxygen saturation during sleeping hours (relative to controls). After treatment, subjects underwent functional magnetic resonance imaging (fMRI) with broadband sound stimulation. Responses are observed in major auditory centers in all subjects, including the auditory cortex (AC) and auditory midbrain. fMRI signals from the AC are statistically significantly increased after CIH by 0.13% in the contralateral hemisphere and 0.10% in the ipsilateral hemisphere. In contrast, signals from the lateral lemniscus of the midbrain are significantly reduced by 0.39%. Signals from the neighboring inferior colliculus of the midbrain are relatively unaffected. Chronic hypoxia affects multiple levels of the auditory system and these changes are likely related to hearing disorders associated with sleep apnea. Copyright © 2017 Elsevier Inc. All rights reserved.

Monitoring and measurement of oxygen concentrations in liquid sodium

International Nuclear Information System (INIS)

Smith, D.L.

1976-01-01

The measurement of oxygen concentrations in sodium at levels of interest for LMFBR applications is reviewed. Additional data are presented to support the validity of the vanadium-equilibration method as a reference for determination of oxygen concentrations in sodium at levels equal to or less than 15 ppM. Operating experience with electrochemical oxygen meters that have a thoria-yttria electrolyte and a Na--Na 2 O reference electrode is described. Meter lifetimes in excess of one year have generally been achieved for operating temperatures of 352 and 402 0 C, and fairly stable emfs have been observed for periods of several months. 7 fig, 21 references

A novel adjustable automated system for inducing chronic intermittent hypoxia in mice.

Science.gov (United States)

Polšek, Dora; Bago, Marcel; Živaljić, Marija; Rosenzweig, Ivana; Lacza, Zsombor; Gajović, Srećko

2017-01-01

Sleep apnea is a chronic, widely underdiagnosed condition characterized by disruption of sleep architecture and intermittent hypoxia due to short cessations of breathing. It is a major independent risk factor for myocardial infarction, congestive heart failure and stroke as well as one of the rare modifiable risk factors for Alzheimer's Dementia. Reliable animal disease models are needed to understand the link between sleep apnea and the various clinically linked disorders. An automated system for inducing hypoxia was developed, in which the major improvement was the possibility to efficiently adjust the length and intensity of hypoxia in two different periods. The chamber used a small volume of gas allowing for fast exchanges of different oxygen levels. The mice were kept in their cages adapted with the system on the cage lid. As a proof of principle, they were exposed to a three week period of intermittent hypoxia for 8 hours a day, with 90 s intervals of 5, 7% and 21% oxygen to validate the model. Treated (n = 8) and control mice (no hypoxia, n = 7) were handled in the same manner and their hippocampal brain regions compared by histology. The chamber provided a fast, reliable and precise intermittent hypoxia, without inducing noticeable side effects to the animals. The validation experiment showed that apoptotic neurons in the hippocampus were more numerous in the mice exposed to intermittent hypoxia than in the control group, in all tested hippocampal regions (cornu ammonis 1 (CA1) P apnea, which was validated by apoptosis of hippocampal neurons.

Hypoxia induces mitochondrial mutagenesis and dysfunction in inflammatory arthritis.

LENUS (Irish Health Repository)

Biniecka, Monika

2012-02-01

OBJECTIVE: To assess the levels and spectrum of mitochondrial DNA (mtDNA) point mutations in synovial tissue from patients with inflammatory arthritis in relation to in vivo hypoxia and oxidative stress levels. METHODS: Random Mutation Capture assay was used to quantitatively evaluate alterations of the synovial mitochondrial genome. In vivo tissue oxygen levels (tPO(2)) were measured at arthroscopy using a Licox probe. Synovial expression of lipid peroxidation (4-hydroxynonenal [4-HNE]) and mitochondrial cytochrome c oxidase subunit II (CytcO II) deficiency were assessed by immunohistochemistry. In vitro levels of mtDNA point mutations, reactive oxygen species (ROS), mitochondrial membrane potential, and markers of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine [8-oxodG]) and lipid peroxidation (4-HNE) were determined in human synoviocytes under normoxia and hypoxia (1%) in the presence or absence of superoxide dismutase (SOD) or N-acetylcysteine (NAC) or a hydroxylase inhibitor (dimethyloxalylglycine [DMOG]). Patients were categorized according to their in vivo tPO(2) level (<20 mm Hg or >20 mm Hg), and mtDNA point mutations, immunochemistry features, and stress markers were compared between groups. RESULTS: The median tPO(2) level in synovial tissue indicated significant hypoxia (25.47 mm Hg). Higher frequency of mtDNA mutations was associated with reduced in vivo oxygen tension (P = 0.05) and with higher synovial 4-HNE cytoplasmic expression (P = 0.04). Synovial expression of CytcO II correlated with in vivo tPO(2) levels (P = 0.03), and levels were lower in patients with tPO(2) <20 mm Hg (P < 0.05). In vitro levels of mtDNA mutations, ROS, mitochondrial membrane potential, 8-oxo-dG, and 4-HNE were higher in synoviocytes exposed to 1% hypoxia (P < 0.05); all of these increased levels were rescued by SOD and DMOG and, with the exception of ROS, by NAC. CONCLUSION: These findings demonstrate that hypoxia-induced mitochondrial dysfunction drives

Antenatal smoking and substance-misuse, infant and newborn response to hypoxia.

Science.gov (United States)

Ali, Kamal; Rosser, Thomas; Bhat, Ravindra; Wolff, Kim; Hannam, Simon; Rafferty, Gerrard F; Greenough, Anne

2017-05-01

To determine at the peak age for sudden infant death syndrome (SIDS) the ventilatory response to hypoxia of infants whose mothers substance misused in pregnancy (SM infants), or smoked during pregnancy (S mothers) and controls whose mothers neither substance misused or smoked. In addition, we compared the ventilatory response to hypoxia during the neonatal period and peak age of SIDS. Infants of S or SM mothers compared to control infants would have a poorer ventilatory response to hypoxia at the peak age of SIDS. Prospective, observational study. Twelve S; 12 SM and 11 control infants were assessed at 6-12 weeks of age and in the neonatal period. Changes in minute volume, oxygen saturation, heart rate, and end tidal carbon dioxide levels on switching from breathing room air to 15% oxygen were assessed. Maternal and infant urine samples were tested for cotinine, cannabinoids, opiates, amphetamines, methadone, cocaine, and benzodiazepines. The S and SM infants had a greater decline in minute volume (P = 0.037, P = 0.016, respectively) and oxygen saturation (P = 0.031) compared to controls. In all groups, the magnitude of decline in minute volume in response to hypoxia was higher in the neonatal period compared to at 6-12 weeks (P ventilatory decline was more marked in the neonatal period compared to the peak age for SIDS indicating a maturational effect. Pediatr Pulmonol. 2017;52:650-655. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of intermittent hypoxia on running economy.

Science.gov (United States)

Burtscher, M; Gatterer, H; Faulhaber, M; Gerstgrasser, W; Schenk, K

2010-09-01

We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy (RE). 11 male and female middle-distance runners were randomly assigned to the intermittent hypoxia group (IHG) or to the control group (CG). All athletes trained for a 13-wk period starting at pre-season until the competition season. The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia (15-11% FiO2). RE, haematological parameters and body composition were determined at low altitude (600 m) at baseline, after the 5 (th), the 8 (th) and the 13 (th) week of training. RE, determined by the relative oxygen consumption during submaximal running, (-2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg, Ptraining phase. Georg Thieme Verlag KG Stuttgart . New York.

Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation.

Directory of Open Access Journals (Sweden)

Laura Asnaghi

Full Text Available The transcriptional response promoted by hypoxia-inducible factors has been associated with metastatic spread of uveal melanoma. We found expression of hypoxia-inducible factor 1α (HIF-1α protein in well-vascularized tumor regions as well as in four cell lines grown in normoxia, thus this pathway may be important even in well-oxygenated uveal melanoma cells. HIF-1α protein accumulation in normoxia was inhibited by rapamycin. As expected, hypoxia (1% pO2 further induced HIF-1α protein levels along with its target genes VEGF and LOX. Growth in hypoxia significantly increased cellular invasion of all 5 uveal melanoma lines tested, as did the introduction of an oxygen-insensitive HIF-1α mutant into Mel285 cells with low HIF-1α baseline levels. In contrast, HIF-1α knockdown using shRNA significantly decreased growth in hypoxia, and reduced by more than 50% tumor invasion in four lines with high HIF-1α baseline levels. Pharmacologic blockade of HIF-1α protein expression using digoxin dramatically suppressed cellular invasion both in normoxia and in hypoxia. We found that Notch pathway components, including Jag1-2 ligands, Hes1-Hey1 targets and the intracellular domain of Notch1, were increased in hypoxia, as well as the phosphorylation levels of Erk1-2 and Akt. Pharmacologic and genetic inhibition of Notch largely blocked the hypoxic induction of invasion as did the pharmacologic suppression of Erk1-2 activity. In addition, the increase in Erk1-2 and Akt phosphorylation by hypoxia was partially reduced by inhibiting Notch signaling. Our findings support the functional importance of HIF-1α signaling in promoting the invasive capacity of uveal melanoma cells in both hypoxia and normoxia, and suggest that pharmacologically targeting HIF-1α pathway directly or through blockade of Notch or Erk1-2 pathways can slow tumor spread.

Hypoxia as a biomarker for radioresistant cancer stem cells.

Science.gov (United States)

Peitzsch, Claudia; Perrin, Rosalind; Hill, Richard P; Dubrovska, Anna; Kurth, Ina

2014-08-01

Tumor initiation, growth and relapse after therapy are thought to be driven by a population of cells with stem cell characteristics, named cancer stem cells (CSC). The regulation of their radiation resistance and their maintenance is poorly understood. CSC are believed to reside preferentially in special microenvironmental niches located within tumor tissues. The features of these niches are of crucial importance for CSC self-renewal, metastatic potential and therapy resistance. One of the characteristics of solid tumors is occurrence of less oxygenated (hypoxic regions), which are believed to serve as so-called hypoxic niches for CSC. The purpose of this review was the critical discussion of the supportive role of hypoxia and hypoxia-related pathways during cancer progression and radiotherapy resistance and the relevance for therapeutic implications in the clinic. It is generally known since decades that hypoxia inside solid tumors impedes chemo- and radiotherapy. However, there is limited evidence to date that targeting hypoxic regions during conventional therapy is effective. Nonetheless improved hypoxia-imaging technologies and image guided individualized hypoxia targeted therapy in conjunction with the development of novel molecular targets may be able to challenge the protective effect on the tumor provided by hypoxia.

Mesenchymal Stem Cells Respond to Hypoxia by Increasing Diacylglycerols.

Science.gov (United States)

Lakatos, Kinga; Kalomoiris, Stefanos; Merkely, Béla; Nolta, Jan A; Fierro, Fernando A

2016-02-01

Mesenchymal stem cells (MSC) are currently being tested clinically for a plethora of conditions, with most approaches relying on the secretion of paracrine signals by MSC to modulate the immune system, promote wound healing, and induce angiogenesis. Hypoxia has been shown to affect MSC proliferation, differentiation, survival and secretory profile. Here, we investigate changes in the lipid composition of human bone marrow-derived MSC after exposure to hypoxia. Using mass spectrometry, we compared the lipid profiles of MSC derived from five different donors, cultured for two days in either normoxia (control) or hypoxia (1% oxygen). Hypoxia induced a significant increase of total triglycerides, fatty acids and diacylglycerols (DG). Remarkably, reduction of DG levels using the phosphatidylcholine-specific phospholipase C inhibitor D609 inhibited the secretion of VEGF and Angiopoietin-2, but increased the secretion of interleukin-8, without affecting significantly their respective mRNA levels. Functionally, incubation of MSC in hypoxia with D609 inhibited the potential of the cells to promote migration of human endothelial cells in a wound/scratch assay. Hence, we show that hypoxia induces in MSC an increase of DG that may affect the angiogenic potential of these cells. © 2015 Wiley Periodicals, Inc.

Critical oxygen tension and the effect of hypoxia on the oxygen consumption of the striped catfish, Pangasius hypophthaimos (Pangasiidae)

DEFF Research Database (Denmark)

Lefevre, S.; Bayley, Mark; Wang, Tobias

2008-01-01

The striped catfish (Pangasius hypophthalmus) is an air-breathing teleost that uses a modified swim bladder for aerial gas exchange. Pangasius is of enormous importance for aquaculture industry in the Mekong Delta(Vietnam), but little is known about its physiology. We have initiated a series...... consumption (VO2), measured with intermittent closed respirometry, was 67.8 ± 5.1 mLO2/kg/h when the fish were maintained without access to air at 27 °C. The critical oxygen tension (Pcrit) at these conditions was 57.9 ± 8.9 mmHg (N = 7). The metabolic response to aquatic hypoxia was studied in fish subjected....... The ontogenetic effect of environmental PO2 on metabolism is currently under investigation with fish being reared in 30%, 60% and 100% saturation. Data on resting VO2and Pcrit will be presented and discussed for these animals....

Effects of natural and human-induced hypoxia on coastal benthos

OpenAIRE

Levin, L. A.; Ekau, W.; Gooday, A. J.; Jorissen, F.; Middelburg, J. J.; Naqvi, S. W. A.; Neira, C.; Rabalais, N. N.; Zhang, J.

2009-01-01

Coastal hypoxia (<1.42 ml L⁻¹; 62.5 μM; 2 mg L⁻¹, approx. 30% oxygen saturation) occurs seasonally in many estuaries, fjords, and along open coasts subject to upwelling or excessive riverine nutrient input, and permanently in some isolated seas and marine basins. Underlying causes of hypoxia include enhanced nutrient input from natural causes (upwelling) or anthropogenic origin (eutrophication) and reduction of mixing by...

Changes in Oxygen Partial Pressure in the Vitreous Body and Arterial Blood of Rabbits Depending on Oxygen Concentration in Inspired Mixture.

Science.gov (United States)

Amkhanitskaya, L I; Nikolaeva, G V; Sokolova, N A

2015-07-01

We demonstrated that the vitreous body of one-month-old rabbits becomes a "reservoir" for storage and accumulation of oxygen after exposure to additional oxygenation of the organism (O2 concentrations in inspired gas mixture were 40, 60, 85, and 99%). The higher was O2 concentration in inspired mixture, the higher was oxygen saturation of the blood and vitreous body. O2 concentration of 40% was relatively safe for eye tissues. O2 concentration >60% induced oxygen accumulation in the vitreous body, which can be a provoking factor for the development of oxygen-induced pathologies.

About Error in Measuring Oxygen Concentration by Solid-Electrolyte Sensors

Directory of Open Access Journals (Sweden)

V. I. Nazarov

2008-01-01

Full Text Available The paper evaluates additional errors while measuring oxygen concentration in a gas mixture by a solid-electrolyte cell. Experimental dependences of additional errors caused by changes in temperature in a sensor zone, discharge of gas mixture supplied to a sensor zone, partial pressure in the gas mixture and fluctuations in oxygen concentrations in the air.

Hypoxia and Its Acid-Base Consequences: From Mountains to Malignancy.

Science.gov (United States)

Swenson, Erik R

Hypoxia, depending upon its magnitude and circumstances, evokes a spectrum of mild to severe acid-base changes ranging from alkalosis to acidosis, which can alter many responses to hypoxia at both non-genomic and genomic levels, in part via altered hypoxia-inducible factor (HIF) metabolism. Healthy people at high altitude and persons hyperventilating to non-hypoxic stimuli can become alkalotic and alkalemic with arterial pH acutely rising as high as 7.7. Hypoxia-mediated respiratory alkalosis reduces sympathetic tone, blunts hypoxic pulmonary vasoconstriction and hypoxic cerebral vasodilation, and increases hemoglobin oxygen affinity. These effects and others can be salutary or counterproductive to tissue oxygen delivery and utilization, based upon magnitude of each effect and summation. With severe hypoxia either in the setting of profound arterial hemoglobin desaturation and reduced O2 content or poor perfusion (ischemia) at the global or local level, metabolic and hypercapnic acidosis develop along with considerable lactate formation and pH falling to below 6.8. Although conventionally considered to be injurious and deleterious to cell function and survival, both acidoses may be cytoprotective by various anti-inflammatory, antioxidant, and anti-apoptotic mechanisms which limit total hypoxic or ischemic-reperfusion injury. Attempts to correct acidosis by giving bicarbonate or other alkaline agents under these circumstances ahead of or concurrent with reoxygenation efforts may be ill advised. Better understanding of this so-called "pH paradox" or permissive acidosis may offer therapeutic possibilities. Rapidly growing cancers often outstrip their vascular supply compromising both oxygen and nutrient delivery and metabolic waste disposal, thus limiting their growth and metastatic potential. However, their excessive glycolysis and lactate formation may not necessarily represent oxygen insufficiency, but rather the Warburg effect-an attempt to provide a large amount

Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

Energy Technology Data Exchange (ETDEWEB)

Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Tsao, Ming-Sound [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, ON M5G2C4 (Canada); Department of Laboratory Medicine and Pathobiology, 27 King’s College Circle, University of Toronto, Toronto, ON M5S1A1 (Canada); Hedley, David W., E-mail: david.hedley@uhn.ca [Ontario Cancer Institute and Campbell Family Cancer Research Institute, Princess Margaret Cancer Center, University Health Network, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medical Biophysics University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Departments of Medicine, University of Toronto, 610 University Ave., Toronto, ON M5G2M9 (Canada); Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, 610 University Ave., Toronto, ON M5G2M9 (Canada)

2014-02-26

The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%–39% between the different models. EF5 labeling in the stroma ranged from 0–20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

Elevation of hypoxia resistance with the use of gutimine

Energy Technology Data Exchange (ETDEWEB)

Vinogradov, V.M.; Pastushenkov, L.V.; Sumina, E.N.

Experimental data demonstrating the protection from the adverse effects of hypoxia offered by the antioxidant gutimine and its analogs are presented. The experiments included preliminary studies of hypoxia resistance and recovery under simulated altitude, studies of circulatory hypoxia in the brain and in intrauterine fetuses, studies of myocardial ischemia during acute and chronic experiments and studies where cardiac, kidney and limb circulation is cut off. The compound was also found to be effective in cases of hemorrhagic hypotension, complex hypoxia in peritonitis, meningococcal meningitis, and the weakening of uterine muscle contractility during prolonged deliveries, and in cranial-cerebral trauma. Mechanisms of the antihypoxic action of gutimine and its analogs have been found to include the reduction of oxygen utilization, the activation of aerobic and anaerobic metabolism, the acceleration of lactate utilization, the inhibition of lipolysis in fat tissue, and stabilization of cell membranes. Clinical observations also support the experimental data.

Gill and lung ventilation responses to steady-state aquatic hypoxia and hyperoxia in the bullfrog tadpole.

Science.gov (United States)

West, N H; Burggren, W W

1982-02-01

Gill ventilation frequency (fG), the pressure amplitude (PBC) and stroke volume (VS) of buccal ventilation cycles, the frequency of air breaths (fL), water flow over the gills (VW), gill oxygen uptake (MGO2), oxygen utilization (U), and heart frequency (fH) have been measured in unanaesthetized, air breathing Rana catesbeiana tadpoles (stage XVI-XIX). The animals were unrestrained except for ECG leads or cannulae, and were able to surface voluntarily for air breathing. They were subjected to aquatic normoxia, hyperoxia and three levels of aquatic hypoxia, and their respiratory responses recorded in the steady state. The experiments were performed at 20 +/- 0.5 degrees C. In hyperoxia there was an absence of air breathing, and fG, PBC and VW fell from the normoxic values, while U increased, resulting in no significant change in MGO2. Animals in normoxia showed a very low fL which increased in progressively more hypoxic states. VW increased from the normoxic value in mild hypoxia (PO2 = 96 +/- 2 mm Hg), but fell, associated with a reduction in PBC, in moderate (PO2 = 41 +/- 1 mm Hg) and severe (PO2 = 21 +/- 3 mm Hg) hypoxia in the presence of lung ventilation. Gill MGO2 was not significantly different from the normoxic value in mild hypoxia but fell in moderate hypoxia, while in severe hypoxia oxygen was lost to the ventilating water from the blood perfusing the gills. There was no significant change in fH from the normoxic value in either hypoxia or hyperoxia. These data indicate, that in the bimodally breathing bullfrog tadpole, aquatic PO2 exerts a strong control over both gill and lung ventilation. Furthermore, there is an interaction between gill and lung ventilation such that the onset of a high frequency of lung ventilation in moderate and severe hypoxia promotes a suppression of gill ventilation cycles.

Hypoxia-inducible factor-1α upregulation in microglia following hypoxia protects against ischemia-induced cerebral infarction.

Science.gov (United States)

Huang, Tao; Huang, Weiyi; Zhang, Zhiqiang; Yu, Lei; Xie, Caijun; Zhu, Dongan; Peng, Zizhuang; Chen, Jiehan

2014-10-01

Activated microglia were considered to be the toxic inflammatory mediators that induce neuron degeneration after brain ischemia. Hypoxia can enhance the expression of hypoxia-inducible factor-1α (HIF-1α) in microglia and cause microglial activation. However, intermittent hypoxia has been reported recently to be capable of protecting the body from myocardial ischemia. We established a high-altitude environment as the hypoxic condition in this study. The hypoxic condition displayed a neuroprotective effect after brain ischemia, and mice exposed to this condition presented better neurological performance and smaller infarct size. At the same time, a high level of HIF-1α, low level of isoform of nitric oxide synthase, and a reduction in microglial activation were also seen in ischemic focus of hypoxic mice. However, this neuroprotective effect could be blocked by 2-methoxyestradiol, the HIF-1α inhibitor. Our finding suggested that HIF-1α expression was involved in microglial activation in vitro and was regulated by oxygen supply. The microglia were inactivated by re-exposure to hypoxia, which might be due to overexpression of HIF-1α. These results indicated that hypoxic conditions can be exploited to achieve maximum neuroprotection after brain ischemia. This mechanism possibly lies in microglial inactivation through regulation of the expression of HIF-1α.

Metabolic Plasticity Enables Circadian Adaptation to Acute Hypoxia in Zebrafish Cells

Directory of Open Access Journals (Sweden)

Adolf M. Sandbichler

2018-04-01

Full Text Available Background/Aims: Reduced oxygen availability, hypoxia, is frequently encountered by organisms, tissues and cells, in aquatic environments as well as in high altitude or under pathological conditions such as infarct, stroke or cancer. The hypoxic signaling pathway was found to be mutually intertwined with circadian timekeeping in vertebrates and, as reported recently, also in mammals. However, the impact of hypoxia on intracellular metabolic oscillations is still unknown. Methods: For determination of metabolites we used Multilabel Reader based fluorescence and luminescence assays, circadian levels of Hypoxia Inducible Factor 1 alpha and oxidized peroxiredoxins were semi quantified by Western blotting and ratiometric quantification of cytosolic and mitochondrial H2O2 was achieved with stable transfections of a redox sensitive green fluorescent protein sensor into zebrafish fibroblasts. Circadian oscillations of core clock gene mRNA´s were assessed using realtime qPCR with subsequent cosine wave fit analysis. Results: Here we show that under normoxia primary metabolic activity of cells predominately occurs during day time and that after acute hypoxia of two hours, administrated immediately before each sampling point, steady state concentrations of glycolytic key metabolites such as glucose and lactate reveal to be highly rhythmic, following a circadian pattern with highest levels during the night periods and reflecting the circadian variation of the cellular response to hypoxia. Remarkably, rhythms in glycolysis are transferred to cellular energy states under normoxic conditions, so that ADP/ATP ratios oscillate as well, which is the first evidence for cycling ADP/ATP pools in a metazoan cell line to our knowledge. Furthermore, the hypoxia induced alterations in rhythms of glycolysis lead to the alignment of three major cellular redox systems, namely the circadian oscillations of NAD+/NADH and NADP+/NADPH ratios and of increased nocturnal levels

Hypoxia promotes Mycobacterium tuberculosis-specific up-regulation of granulysin in human T cells.

Science.gov (United States)

Zenk, Sebastian F; Vollmer, Michael; Schercher, Esra; Kallert, Stephanie; Kubis, Jan; Stenger, Steffen

2016-06-01

Oxygen tension affects local immune responses in inflammation and infection. In tuberculosis mycobacteria avoid hypoxic areas and preferentially persist and reactivate in the oxygen-rich apex of the lung. Oxygen restriction activates antimicrobial effector mechanisms in macrophages and restricts growth of intracellular Mycobacterium tuberculosis (M.Tb). The effect of oxygen restriction on T cell-mediated antimicrobial effector mechanisms is unknown. Therefore we determined the influence of hypoxia on the expression of granulysin, an antimicrobial peptide of lymphocytes. Hypoxia increased the antigen-specific up-regulation of granulysin mRNA and protein in human CD4(+) and CD8(+) T lymphocytes. This observation was functionally relevant, because oxygen restriction supported the growth-limiting effect of antigen-specific T cells against virulent M.Tb residing in primary human macrophages. Our results provide evidence that oxygen restriction promotes the expression of granulysin and suggest that this effect-in conjunction with additional T cell-mediated immune responses-supports protection against mycobacteria. The therapeutic modulation of oxygen availability may offer a new strategy for the host-directed therapy of infectious diseases with intracellular pathogens.

Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension

Science.gov (United States)

Naik, Jay S.; Weise-Cross, Laura; Detweiler, Neil D.; Herbert, Lindsay M.; Yellowhair, Tracylyn R.; Resta, Thomas C.

2017-01-01

Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension. SU5416 is a vascular endothelial growth factor receptor antagonist and the combination of chronic hypoxia/SU5416 produces a model of severe pulmonary arterial hypertension with vascular plexiform lesions/fibrosis that is not present with chronic hypoxia alone. The major findings from this study are: 1) compared to hypoxia alone, hypoxia/SU5416 exposure caused more severe pulmonary hypertension, right ventricular hypertrophy, adventitial lesion formation, and greater vasoconstrictor sensitivity through a superoxide and Rho kinase-dependent Ca2+ sensitization mechanism. 2) Chronic hypoxia increased medial muscularization and superoxide levels, however there was no effect of SU5416 to augment these responses. 3) Treatment with TEMPOL decreased right ventricular systolic pressure in both hypoxia and hypoxia/SU5416 groups. 4) This effect of TEMPOL was associated with normalization of vasoconstrictor responses, but not arterial remodeling. Rather, medial hypertrophy and adventitial fibrotic lesion formation were more pronounced following chronic TEMPOL treatment in hypoxia/SU5416 rats. Our findings support a major role for reactive oxygen species in mediating enhanced vasoconstrictor reactivity and pulmonary hypertension in both chronic hypoxia and hypoxia/SU5416 rat models, despite a

Renal transplantation induces mitochondrial uncoupling, increased kidney oxygen consumption, and decreased kidney oxygen tension

NARCIS (Netherlands)

Papazova, Diana A.; Friederich-Persson, Malou; Joles, Jaap A.; Verhaar, Marianne C.

2015-01-01

Hypoxia is an acknowledged pathway to renal injury and ischemia-reperfusion (I/R) and is known to reduce renal oxygen tension (PO2). We hypothesized that renal I/R increases oxidative damage and induces mitochondrial uncoupling, resulting in increased oxygen consumption and hence kidney

Effect of hypoxia on BOLD fMRI response and total cerebral blood flow in migraine with aura patients

DEFF Research Database (Denmark)

Arngrim, Nanna; Hougaard, Anders; Schytz, Henrik W

2018-01-01

was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA......Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double......-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation...

Ontogenetic Responses of Calanus chilensis to Hypoxia from Northern Chile (23ºS), Humboldt Current Ecosystem

Science.gov (United States)

Ruz, P. M.; Hidalgo, P.; Escribano, R.; Franco-Cisterna, B.; Yebra, L.; Keister, J. E.

2016-02-01

Eastern Boundary Upwelling Systems are being subjected to expansion, intensification and shoaling of Oxygen Minimum Zones (OMZ's), as a result of ongoing climate change. To understand how dominant epipelagic copepods may respond to stressful conditions induced by low oxygen, we experimentally studied the effect of hypoxia over the stage-specific physiology of Calanus chilensis from the Mejillones Bay (23°S — 70°W), northern Chile, during the winters of 2013 and 2014. Females, eggs and nauplii (NI to NIV) of C. chilensis were incubated under hypoxia ( 0.7 mg O2 L-1) and normoxia ( 8.3 mg O2 L-1) conditions at a constant temperature of 14ºC as to estimate egg production rate (EPR), hatching success (HS) and naupliar growth and development time. Additionally, we estimated survivorship by using Neutral Red technique, and also examined female metabolism by measuring specific activity of the enzymes Aminoacyl-tRNA synthetases (spAARS) (growth index) and the electron transport system (spETS) (potential respiration). Survival of females and EPR were not significantly affected by dissolved oxygen (DO) conditions, coinciding with no significant changes in their metabolism. By contrast, HS was reduced from normoxia (70%) to hypoxia (30%), whereas naupliar growth (NI to NIII) was lower under hypoxia (0.155 ± 0.007 d-1) than normoxia (0.237 ± 0.006 d-1), resulting also in a longer development time, 6.490 ± 0.353 d and 4.238 ± 0.149 d, respectively. Most eggs and nauplii collected at the end of the experiments were alive, although a higher proportion of organisms were recovered in normoxia than hypoxia. Our results revealed stage-specific responses to hypoxia in C. chilensis and the importance of ontogenetic responses to variable levels of oxygenation in the upwelling zone.

Cuticle ultrastructure, cuticular lipid composition, and gene expression in hypoxia-stressed Arabidopsis stems and leaves.

Science.gov (United States)

Kim, Hyojin; Choi, Dongsu; Suh, Mi Chung

2017-06-01

An increased permeability of the cuticle is closely associated with downregulation of genes involved in cuticular lipid synthesis in hypoxia-stressed Arabidopsis and may allow plants to cope with oxygen deficiency. The hydrophobic cuticle layer consisting of cutin polyester and cuticular wax is the first barrier to protect the aerial parts of land plants from environmental stresses. In the present study, we investigated the role of cuticle membrane in Arabidopsis responses to oxygen deficiency. TEM analysis showed that the epidermal cells of hypoxia-treated Arabidopsis stems and leaves possessed a thinner electron-translucent cuticle proper and a more electron-dense cuticular layer. A reduction in epicuticular wax crystal deposition was observed in SEM images of hypoxia-treated Arabidopsis stem compared with normoxic control. Cuticular transpiration was more rapid in hypoxia-stressed leaves than in normoxic control. Total wax and cutin loads decreased by approximately 6-12 and 12-22%, respectively, and the levels of C29 alkanes, secondary alcohols, and ketones, C16:0 ω-hydroxy fatty acids, and C18:2 dicarboxylic acids were also prominently reduced in hypoxia-stressed Arabidopsis leaves and/or stems relative to normoxic control. Genome-wide transcriptome and quantitative RT-PCR analyses revealed that the expression of several genes involved in the biosynthesis and transport of cuticular waxes and cutin monomers were downregulated more than fourfold, but no significant alterations were detected in the transcript levels of fatty acid biosynthetic genes, BCCP2, PDH-E1α, and ENR1 in hypoxia-treated Arabidopsis stems and leaves compared with normoxic control. Taken together, an increased permeability of the cuticle is closely associated with downregulation of genes involved in cuticular lipid synthesis in hypoxia-stressed Arabidopsis. The present study elucidates one of the cuticle-related adaptive responses that may allow plants to cope with low oxygen levels.

Impact of urban effluents on summer hypoxia in the highly turbid Gironde Estuary, applying a 3D model coupling hydrodynamics, sediment transport and biogeochemical processes

Science.gov (United States)

Lajaunie-Salla, Katixa; Wild-Allen, Karen; Sottolichio, Aldo; Thouvenin, Bénédicte; Litrico, Xavier; Abril, Gwenaël

2017-10-01

Estuaries are increasingly degraded due to coastal urban development and are prone to hypoxia problems. The macro-tidal Gironde Estuary is characterized by a highly concentrated turbidity maximum zone (TMZ). Field observations show that hypoxia occurs in summer in the TMZ at low river flow and a few days after the spring tide peak. In situ data highlight lower dissolved oxygen (DO) concentrations around the city of Bordeaux, located in the upper estuary. Interactions between multiple factors limit the understanding of the processes controlling the dynamics of hypoxia. A 3D biogeochemical model was developed, coupled with hydrodynamics and a sediment transport model, to assess the contribution of the TMZ and the impact of urban effluents through wastewater treatment plants (WWTPs) and sewage overflows (SOs) on hypoxia. Our model describes the transport of solutes and suspended material and the biogeochemical mechanisms impacting oxygen: primary production, degradation of all organic matter (i.e. including phytoplankton respiration, degradation of river and urban watershed matter), nitrification and gas exchange. The composition and the degradation rates of each variable were characterized by in situ measurements and experimental data from the study area. The DO model was validated against observations in Bordeaux City. The simulated DO concentrations show good agreement with field observations and satisfactorily reproduce the seasonal and neap-spring time scale variations around the city of Bordeaux. Simulations show a spatial and temporal correlation between the formation of summer hypoxia and the location of the TMZ, with minimum DO centered in the vicinity of Bordeaux. To understand the contribution of the urban watershed forcing, different simulations with the presence or absence of urban effluents were compared. Our results show that in summer, a reduction of POC from SO would increase the DO minimum in the vicinity of Bordeaux by 3% of saturation. Omitting

Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

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Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

2009-08-06

Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

International Nuclear Information System (INIS)

Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

2009-01-01

Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

Fatty Acid Uptake and Lipid Storage Induced by HIF-1α Contribute to Cell Growth and Survival after Hypoxia-Reoxygenation

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Karim Bensaad

2014-10-01

Full Text Available Summary: An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3 and FABP7, both of which are involved in fatty acid uptake. In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α-dependent manner. There was a significant lipid droplet (LD accumulation in hypoxia that was time and O2 concentration dependent. Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component significantly impaired LD formation under hypoxia. We showed that LD accumulation is due to FABP3/7-dependent fatty acid uptake while de novo fatty acid synthesis is repressed in hypoxia. We also showed that ATP production occurs via β-oxidation or glycogen degradation in a cell-type-dependent manner in hypoxia-reoxygenation. Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. : Bensaad et al. now show that FABP3 and FABP7 are induced by HIF-1α and lead to a significant lipid droplet (LD accumulation in hypoxia. In hypoxia-reoxygenation, ATP production occurs via fatty acid β-oxidation or glycogen degradation in a cell-type-dependent manner, while inhibition of LD formation increases ROS toxicity and decreases cell survival in vitro and strongly impairs tumorigenesis in vivo.

Methane oxidation and formation of EPS in compost: effect of oxygen concentration

International Nuclear Information System (INIS)

Wilshusen, J.H.; Hettiaratchi, J.P.A.; Visscher, A. de; Saint-Fort, R.

2004-01-01

Oxygen concentration plays an important role in the regulation of methane oxidation and the microbial ecology of methanotrophs. However, this effect is still poorly quantified in soil and compost ecosystems. The effect of oxygen on the formation of exopolymeric substances (EPS) is as yet unknown. We studied the effect of oxygen on the evolution of methanotrophic activity. At both high and low oxygen concentrations, peak activity was observed twice within a period of 6 months. Phospholipid fatty acid analysis showed that there was a shift from type I to type II methanotrophs during this period. At high oxygen concentration, EPS production was about 250% of the amount at low oxygen concentration. It is hypothesized that EPS serves as a carbon cycling mechanism for type I methanotrophs when inorganic nitrogen is limiting. Simultaneously, EPS stimulates nitrogenase activity in type II methanotrophs by creating oxygen-depleted zones. The kinetic results were incorporated in a simulation model for gas transport and methane oxidation in a passively aerated biofilter. Comparison between the model and experimental data showed that, besides acting as a micro-scale diffusion barrier, EPS can act as a barrier to macro-scale diffusion, reducing the performance of such biofilters. - 1.5% oxygen resulted in a slightly higher and more stable methane oxidation activity

Hypoxia Impacts on Food Web Linkages in a Pelagic Ecosystem

Science.gov (United States)

Sato, M.; Horne, J. K.; Parker-Stetter, S. L.; Essington, T.; Keister, J. E.; Moriarty, P.; Li, L.

2016-02-01

Low dissolved oxygen (DO), or hypoxia, causes significant disturbances on aquatic organisms, but the consequences for key food web linkages is not well understood. Here, we tested how the intensity of low DO events governs the degree of spatial overlap between pelagic zooplanktivorous fish and their zooplankton prey, fish feeding rates, and community compositions of zooplankton. We hypothesized that the greater sensitivity of fish to DO compared to zooplankton would lead to diminished spatial overlap at moderate DO and reduced feeding rates of fish, while severe hypoxia would amplify spatial overlap by preventing zooplankton from using deep refuge habitats leading to increased fish feeding rates. We also hypothesized shifts in zooplankton community composition towards less energetically profitable taxa such as small copepods and gelatinous species. We used a combination of multifrequency acoustic and net sampling for detecting distributions and abundance of zooplankton and pelagic fish in Hood Canal, WA, a seasonally hypoxic fjord. We employed a sampling design which paired hypoxic regions of Hood Canal with normoxic regions sampled prior to, during, and after the onset of hypoxia in two years. Contrary to our hypotheses, we found that fish and zooplankton did not change their horizontal and vertical distributions during periods and in locations with low DO levels. Consequently, the vertical overlap between fish and zooplankton did not change with DO. Fish feeding rates and the dominant zooplankton prey did not change with hypoxia events. The apparent resilience of fish to low DO in our system may be explained by decreased metabolic oxygen demand due to cool temperatures, increased availability and accessibility to their prey in low DO waters, or potential increase in predation risk at shallower depth. This study highlights the importance of both temperature and DO, instead of hypoxia threshold alone, in evaluating the impacts of hypoxia on pelagic communities.

Anti-vascular agent Combretastatin A-4-P modulates Hypoxia Inducible Factor-1 and gene expression

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Currie Margaret J

2006-12-01

Full Text Available Abstract Background A functional vascular network is essential for the survival, growth and spread of solid tumours, making blood vessels a key target for therapeutic strategies. Combretastatin A-4 phosphate (CA-4-P is a tubulin-depolymerising agent in Phase II clinical trials as a vascular disrupting agent. Not much is known of the molecular effect of CA-4-P under tumour conditions. The tumour microenvironment differs markedly from that in normal tissue, specifically with respect to oxygenation (hypoxia. Gene regulation under tumour conditions is governed by hypoxia inducible factor 1 (HIF-1, controlling angiogenic and metastatic pathways. Methods We investigated the effect of CA-4-P on factors of the upstream and downstream signalling pathway of HIF-1 in vitro. Results CA-4-P treatment under hypoxia tended to reduce HIF-1 accumulation in a concentration-dependent manner, an effect which was more prominent in endothelial cells than in cancer cell lines. Conversely, CA-4-P increased HIF-1 accumulation under aerobic conditions in vitro. At these concentrations of CA-4-P under aerobic conditions, nuclear factor κB was activated via the small GTPase RhoA, and expression of the HIF-1 downstream angiogenic effector gene, vascular endothelial growth factor (VEGF-A, was increased. Conclusion Our findings advance the understanding of signal transduction pathways involved in the actions of the anti-vascular agent CA-4-P.

Introduction of high oxygen concentrations into silicon wafers by high-temperature diffusion

International Nuclear Information System (INIS)

Casse, G.; Glaser, M.; Lemeilleur, F.; Ruzin, A.; Wegrzecki, M.

1999-01-01

The tolerance of silicon detectors to hadron irradiation can be improved by the introduction of a high concentration of oxygen into the starting material. High-resistivity Floating-Zone (FZ) silicon is required for detectors used in particle physics applications. A significantly high oxygen concentration (>10 17 atoms cm -3 ) cannot readily be achieved during the FZ silicon refinement. The diffusion of oxygen at elevated temperatures from a SiO 2 layer grown on both sides of a silicon wafer is a simple and effective technique to achieve high and uniform concentrations of oxygen throughout the bulk of a 300 μm thick silicon wafer

Hypoxia-induced oxidative base modifications in the VEGF hypoxia-response element are associated with transcriptionally active nucleosomes.

Science.gov (United States)

Ruchko, Mykhaylo V; Gorodnya, Olena M; Pastukh, Viktor M; Swiger, Brad M; Middleton, Natavia S; Wilson, Glenn L; Gillespie, Mark N

2009-02-01

Reactive oxygen species (ROS) generated in hypoxic pulmonary artery endothelial cells cause transient oxidative base modifications in the hypoxia-response element (HRE) of the VEGF gene that bear a conspicuous relationship to induction of VEGF mRNA expression (K.A. Ziel et al., FASEB J. 19, 387-394, 2005). If such base modifications are indeed linked to transcriptional regulation, then they should be detected in HRE sequences associated with transcriptionally active nucleosomes. Southern blot analysis of the VEGF HRE associated with nucleosome fractions prepared by micrococcal nuclease digestion indicated that hypoxia redistributed some HRE sequences from multinucleosomes to transcriptionally active mono- and dinucleosome fractions. A simple PCR method revealed that VEGF HRE sequences harboring oxidative base modifications were found exclusively in mononucleosomes. Inhibition of hypoxia-induced ROS generation with myxathiozol prevented formation of oxidative base modifications but not the redistribution of HRE sequences into mono- and dinucleosome fractions. The histone deacetylase inhibitor trichostatin A caused retention of HRE sequences in compacted nucleosome fractions and prevented formation of oxidative base modifications. These findings suggest that the hypoxia-induced oxidant stress directed at the VEGF HRE requires the sequence to be repositioned into mononucleosomes and support the prospect that oxidative modifications in this sequence are an important step in transcriptional activation.

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302.

Science.gov (United States)

Wojtkowiak, Jonathan W; Cornnell, Heather C; Matsumoto, Shingo; Saito, Keita; Takakusagi, Yoichi; Dutta, Prasanta; Kim, Munju; Zhang, Xiaomeng; Leos, Rafael; Bailey, Kate M; Martinez, Gary; Lloyd, Mark C; Weber, Craig; Mitchell, James B; Lynch, Ronald M; Baker, Amanda F; Gatenby, Robert A; Rejniak, Katarzyna A; Hart, Charles; Krishna, Murali C; Gillies, Robert J

2015-01-01

Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clinical HAPs activity could be improved. In this study, we sought to identify non-pharmacological methods to acutely exacerbate tumor hypoxia to increase TH-302 activity in pancreatic ductal adenocarcinoma (PDAC) tumor models. Three human PDAC cell lines with varying sensitivity to TH-302 (Hs766t > MiaPaCa-2 > SU.86.86) were used to establish PDAC xenograft models. PDAC cells were metabolically profiled in vitro and in vivo using the Seahorse XF system and hyperpolarized (13)C pyruvate MRI, respectively, in addition to quantitative immunohistochemistry. The effect of exogenous pyruvate on tumor oxygenation was determined using electroparamagnetic resonance (EPR) oxygen imaging. Hs766t and MiaPaCa-2 cells exhibited a glycolytic phenotype in comparison to TH-302 resistant line SU.86.86. Supporting this observation is a higher lactate/pyruvate ratio in Hs766t and MiaPaCa xenografts as observed during hyperpolarized pyruvate MRI studies in vivo. Coincidentally, response to exogenous pyruvate both in vitro (Seahorse oxygen consumption) and in vivo (EPR oxygen imaging) was greatest in Hs766t and MiaPaCa models, possibly due to a higher mitochondrial reserve capacity. Changes in oxygen consumption and in vivo hypoxic status to pyruvate were limited in the SU.86.86 model. Combination therapy of pyruvate plus TH-302 in vivo significantly decreased tumor growth and increased survival in the MiaPaCa model and improved survival in Hs766t tumors. Using metabolic profiling, functional imaging, and computational modeling, we show improved TH-302 activity by transiently increasing tumor hypoxia metabolically with exogenous pyruvate. Additionally, this work identified a set of biomarkers that may be used clinically to predict which tumors will be most responsive to

Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

DEFF Research Database (Denmark)

Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

2003-01-01

Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming...

Immunohistochemical detection of osteopontin in advanced head-and-neck cancer: Prognostic role and correlation with oxygen electrode measurements, hypoxia-inducible-factor-1α-related markers, and hemoglobin levels

International Nuclear Information System (INIS)

Bache, Matthias; Reddemann, Rolf; Said, Harun M.; Holzhausen, Hans-Juergen; Taubert, Helge; Becker, Axel; Kuhnt, Thomas; Haensgen, Gabriele; Dunst, Juergen; Vordermark, Dirk

2006-01-01

Purpose: The tumor-associated glycoprotein osteopontin (OPN) is discussed as a plasma marker of tumor hypoxia. However, the association of immunohistochemical OPN expression in tumor sections with tumor oxygenation parameters (HF5, median pO 2 ), the hypoxia-related markers hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CAIX), or hemoglobin and systemic vascular endothelial growth factor (VEGF) levels has not been investigated. Methods and Materials: Tumor tissue sections of 34 patients with advanced head-and-neck cancer treated with radiotherapy were assessed by immunochemistry for the expression of OPN, HIF-1α, and CA IX. Relationship of OPN expression with tumor oxygenation parameters (HF5, median pO 2 ), HIF-1α and CA IX expression, hemoglobin and serum VEGF level, and clinical parameters was studied. Results: Bivariate analysis showed a significant correlation of positive OPN staining with low hemoglobin level (p = 0.02), high HIF-1α expression (p = 0.02), and high serum vascular endothelial growth factor level (p = 0.02) for advanced head-and-neck cancer. Furthermore, considering the 31 Stage IV patients, the median pO 2 correlated significantly with the OPN expression (p = 0.02). OPN expression alone had only a small impact on prognosis. However, in a univariate Cox proportional hazard regression model, the expression of either OPN or HIF-1α or CA IX was associated with a 4.1-fold increased risk of death (p = 0.02) compared with negativity of all three markers. Conclusion: Osteopontin expression detected immunohistochemically is associated with oxygenation parameters in advanced head-and-neck cancer. When the results of OPN, HIF-1α, and CA IX immunohistochemistry are combined into a hypoxic profile, a strong and statistically significant impact on overall survival is found

Changes in Muscle and Cerebral Deoxygenation and Perfusion during Repeated Sprints in Hypoxia to Exhaustion

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Sarah J. Willis

2017-10-01

Full Text Available During supramaximal exercise, exacerbated at exhaustion and in hypoxia, the circulatory system is challenged to facilitate oxygen delivery to working tissues through cerebral autoregulation which influences fatigue development and muscle performance. The aim of the study was to evaluate the effects of different levels of normobaric hypoxia on the changes in peripheral and cerebral oxygenation and performance during repeated sprints to exhaustion. Eleven recreationally active participants (six men and five women; 26.7 ± 4.2 years, 68.0 ± 14.0 kg, 172 ± 12 cm, 14.1 ± 4.7% body fat completed three randomized testing visits in conditions of simulated altitude near sea-level (~380 m, FIO2 20.9%, ~2000 m (FIO2 16.5 ± 0.4%, and ~3800 m (FIO2 13.3 ± 0.4%. Each session began with a 12-min warm-up followed by two 10-s sprints and the repeated cycling sprint (10-s sprint: 20-s recovery test to exhaustion. Measurements included power output, vastus lateralis, and prefrontal deoxygenation [near-infrared spectroscopy, delta (Δ corresponds to the difference between maximal and minimal values], oxygen uptake, femoral artery blood flow (Doppler ultrasound, hemodynamic variables (transthoracic impedance, blood lactate concentration, and rating of perceived exertion. Performance (total work, kJ; −27.1 ± 25.8% at 2000 m, p < 0.01 and −49.4 ± 19.3% at 3800 m, p < 0.001 and pulse oxygen saturation (−7.5 ± 6.0%, p < 0.05 and −18.4 ± 5.3%, p < 0.001, respectively decreased with hypoxia, when compared to 400 m. Muscle Δ hemoglobin difference ([Hbdiff] and Δ tissue saturation index (TSI were lower (p < 0.01 at 3800 m than at 2000 and 400 m, and lower Δ deoxyhemoglobin resulted at 3800 m compared with 2000 m. There were reduced changes in peripheral [Δ[Hbdiff], ΔTSI, Δ total hemoglobin ([tHb

Osmotic phenomena in application for hyperbaric oxygen treatment.

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Babchin, A; Levich, E; Melamed M D, Y; Sivashinsky, G

2011-03-01

Hyperbaric oxygen (HBO) treatment defines the medical procedure when the patient inhales pure oxygen at elevated pressure conditions. Many diseases and all injuries are associated with a lack of oxygen in tissues, known as hypoxia. HBO provides an effective method for fast oxygen delivery in medical practice. The exact mechanism of the oxygen transport under HBO conditions is not fully identified. The objective of this article is to extend the colloid and surface science basis for the oxygen transport in HBO conditions beyond the molecular diffusion transport mechanism. At a pressure in the hyperbaric chamber of two atmospheres, the partial pressure of oxygen in the blood plasma increases 10 times. The sharp increase of oxygen concentration in the blood plasma creates a considerable concentration gradient between the oxygen dissolved in the plasma and in the tissue. The concentration gradient of oxygen as a non-electrolyte solute causes an osmotic flow of blood plasma with dissolved oxygen. In other words, the molecular diffusion transport of oxygen is supplemented by the convective diffusion raised due to the osmotic flow, accelerating the oxygen delivery from blood to tissue. A non steady state equation for non-electrolyte osmosis is solved asymptotically. The solution clearly demonstrates two modes of osmotic flow: normal osmosis, directed from lower to higher solute concentrations, and anomalous osmosis, directed from higher to lower solute concentrations. The fast delivery of oxygen from blood to tissue is explained on the basis of the strong molecular interaction between the oxygen and the tissue, causing an influx of oxygen into the tissue by convective diffusion in the anomalous osmosis process. The transport of the second gas, nitrogen, dissolved in the blood plasma, is also taken into the consideration. As the patient does not inhale nitrogen during HBO treatment, but exhales it along with oxygen and carbon dioxide, the concentration of nitrogen in blood

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

Science.gov (United States)

Hals, I. K.; Rokstad, A. M.; Strand, B. L.; Oberholzer, J.; Grill, V.

2013-01-01

Islet transplantation in diabetes is hampered by the need of life-long immunosuppression. Encapsulation provides partial immunoprotection but could possibly limit oxygen supply, a factor that may enhance hypoxia-induced beta cell death in the early posttransplantation period. Here we tested susceptibility of alginate microencapsulated human islets to experimental hypoxia (0.1–0.3% O2 for 8 h, followed by reoxygenation) on viability and functional parameters. Hypoxia reduced viability as measured by MTT by 33.8 ± 3.5% in encapsulated and 42.9 ± 5.2% in nonencapsulated islets (P microencapsulation of human islets does not increase susceptibility to acute hypoxia. This is a positive finding in relation to potential use of encapsulation for islet transplantation. PMID:24364039

Hypoxanthine as a measurement of hypoxia.

Science.gov (United States)

Saugstad, O D

1975-04-01

The hypoxanthine concentration in plasma was found to be a sensitive parameter of hypoxia of the fetus and the newborn infant. The plasma level of hypoxanthine in the umbilical cord in 29 newborn infants with normal delivery varied between 0 and 11.0 mumol/liter with a mean of 5.8 mumol/liter, SD 3.0 mumol/liter. Compared with this reference group the hypoxanthine concentration in plasma of the umbilical cord in 10 newborn infants with clinical signs of intrauterine hypoxia during labor was found to be significantly higher, with a range of 11.0-61.5 mumol/liter, with a mean of 25.0 mumol/liter, SD 18.0 mumol/liter. The plasma level of hypoxanthine in two premature babies developing an idiopathic respiratory distress syndrome was monitored. The metabolite was found to be considerably increased, in one of them more than 24 hr after a period of hypoxia necessitating artificial ventilation. The hypoxanthine level in plasma of umbilical arterial blood was followed about 2 hr postpartum in three newborn infants with clinical signs of intrauterine hypoxia. The decrease of the plasma concentration of the metabolite seemed to be with a constant velocity, as it was about 10 mumol/liter/hr in these cases. A new method was used for the determination of hypoxanthine in plasma, based on the principle that PO2 decreased when hypoxanthine is oxidized to uric acid.

Zeaxanthin Inhibits Hypoxia-Induced VEGF Secretion by RPE Cells through Decreased Protein Levels of Hypoxia-Inducible Factors-1α

Directory of Open Access Journals (Sweden)

Richard Rosen

2015-01-01

Full Text Available Hypoxia is the most important stimulus leading to upregulation of VEGF in the retina and this is caused by accumulation of hypoxia-inducible factors-1α (HIF-1α protein. The effects of zeaxanthin, a natural phytochemical, on the VEGF and HIF-1α expression in the primary culture of human retinal pigment epithelial (RPE cells were studied. An in vitro RPE cell hypoxia model was established by placing cells under 1% oxygen pressure or by adding cobalt chloride (CoCl2 to the culture medium. RPE cells and conditioned media were collected from cultures treated with and without zeaxanthin under normoxic and hypoxic conditions. VEGF and HIF-1α protein and RNA levels were measured by ELISA kits and RT-PCR, respectively. Hypoxia caused a significant increase of VEGF expression and accumulation of HIF-1α in RPE cells. Zeaxanthin at 50–150 μM significantly inhibited the expression of VEGF and accumulation of HIF-1α protein caused by hypoxia but did not affect expression of VEGF and HIF-1α under normoxic conditions. This is the first report on the effect of zeaxanthin on VEGF and HIF-1α levels in cultured RPE cells and suggests that zeaxanthin may have potential value in the prevention and treatment of various retinal diseases associated with vascular leakage and neovascularization.