scholarly journals Acute hypoxia-reoxygenation and vascular oxygen sensing in the chicken embryo

2017 ◽  
Vol 5 (22) ◽  
pp. e13501
Author(s):  
Riazuddin Mohammed ◽  
Carlos E. Salinas ◽  
Dino A. Giussani ◽  
Carlos E. Blanco ◽  
Angel L. Cogolludo ◽  
...  
Keyword(s):  
Chicken Embryo ◽  
Oxygen Sensing ◽  
Acute Hypoxia ◽  
Hypoxia Reoxygenation

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

2002 ◽  
Vol 283 (2) ◽  
pp. R331-R338 ◽  
Author(s):  
K. Ruijtenbeek ◽  
C. G. A. Kessels ◽  
E. Villamor ◽  
C. E. Blanco ◽  
J. G. R. De Mey
Keyword(s):  
Chicken Embryo ◽  
Acute Hypoxia ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Direct Effects ◽  
No Donor ◽  
Femoral Arteries ◽  
Contraction And Relaxation

In the chicken embryo, acute hypoxemia results in cardiovascular responses, including an increased peripheral resistance. We investigated whether local direct effects of decreased oxygen tension might participate in the arterial response to hypoxemia in the chicken embryo. Femoral arteries of chicken embryos were isolated at 0.9 of incubation time, and the effects of acute hypoxia on contraction and relaxation were determined in vitro. While hypoxia reduced contraction induced by high K+ to a small extent (−21.8 ± 5.7%), contractile responses to exogenous norepinephrine (NE) were markedly reduced (−51.1 ± 3.2%) in 80% of the arterial segments. This effect of hypoxia was not altered by removal of the endothelium, inhibition of NO synthase or cyclooxygenase, or by depolarization plus Ca2+ channel blockade. When arteries were simultaneously exposed to NE and ACh, hypoxia resulted in contraction (+49.8 ± 9.3%). Also, relaxing responses to ACh were abolished during acute hypoxia, while the vessels became more sensitive to the relaxing effect of the NO donor sodium nitroprusside (pD2: 5.81 ± 0.21 vs. 5.31 ± 0.27). Thus, in chicken embryo femoral arteries, acute hypoxia blunts agonist-induced contraction of the smooth muscle and inhibits stimulated endothelium-derived relaxation factor release. The consequences of this for in vivo fetal hemodynamics during acute hypoxemia depend on the balance between vasomotor influences of circulating catecholamines and those of the endothelium.

scholarly journals Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing

2020 ◽  
Vol 6 (16) ◽  
pp. eaba0694 ◽  
Author(s):  
Natascha Sommer ◽  
Nasim Alebrahimdehkordi ◽  
Oleg Pak ◽  
Fenja Knoepp ◽  
Ievgen Strielkov ◽  
...  
Keyword(s):  
Alternative Oxidase ◽  
Chronic Hypoxia ◽  
Electron Flux ◽  
Oxygen Sensing ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factor ◽  
Initial Step ◽  
Complex Iii ◽  
Pulmonary Vasculature

Mitochondria play an important role in sensing both acute and chronic hypoxia in the pulmonary vasculature, but their primary oxygen-sensing mechanism and contribution to stabilization of the hypoxia-inducible factor (HIF) remains elusive. Alteration of the mitochondrial electron flux and increased superoxide release from complex III has been proposed as an essential trigger for hypoxic pulmonary vasoconstriction (HPV). We used mice expressing a tunicate alternative oxidase, AOX, which maintains electron flux when respiratory complexes III and/or IV are inhibited. Respiratory restoration by AOX prevented acute HPV and hypoxic responses of pulmonary arterial smooth muscle cells (PASMC), acute hypoxia-induced redox changes of NADH and cytochrome c, and superoxide production. In contrast, AOX did not affect the development of chronic hypoxia-induced pulmonary hypertension and HIF-1α stabilization. These results indicate that distal inhibition of the mitochondrial electron transport chain in PASMC is an essential initial step for acute but not chronic oxygen sensing.

Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells

2005 ◽  
Vol 288 (4) ◽  
pp. L749-L760 ◽  
Author(s):  
Beata Wojciak-Stothard ◽  
Lillian Yen Fen Tsang ◽  
Sheila G. Haworth
Keyword(s):  
Nadph Oxidase ◽  
Rho Gtpases ◽  
Adherens Junctions ◽  
Acute Hypoxia ◽  
Endothelial Permeability ◽  
Pi3 Kinase ◽  
Fiber Formation ◽  
Dominant Negative ◽  
Induced Changes ◽  
Hypoxia Reoxygenation

Hypoxia/reoxygenation-induced changes in endothelial permeability are accompanied by endothelial actin cytoskeletal and adherens junction remodeling, but the mechanisms involved are uncertain. We therefore measured the activities of the Rho GTPases Rac1, RhoA, and Cdc42 during hypoxia/reoxygenation and correlated them with changes in endothelial permeability, remodeling of the actin cytoskeleton and adherens junctions, and production of ROS. Dominant negative forms of Rho GTPases were introduced into cells by adenoviral gene transfer and transfection, and inhibitors of NADPH oxidase, PI3 kinase, and Rho kinase were used to characterize the signaling pathways involved. In some experiments constitutively activated forms of RhoA and Rac1 were also used. We show for the first time that hypoxia/reoxygenation-induced changes in endothelial permeability result from coordinated actions of the Rho GTPases Rac1 and RhoA. Rac1 and RhoA rapidly respond to changes in oxygen tension, and their activity depends on NADPH oxidase- and PI3 kinase-dependent production of ROS. Rac1 acts upstream of RhoA, and its transient inhibition by acute hypoxia leads to activation of RhoA followed by stress fiber formation, dispersion of adherens junctions, and increased endothelial permeability. Reoxygenation strongly activates Rac1 and restores cortical localization of F-actin and VE-cadherin. This effect is a result of Rac1-mediated inhibition of RhoA and can be prevented by activators of RhoA, L63RhoA, and lysophosphatidic acid. Cdc42 activation follows the RhoA pattern of activation but has no effect on actin remodeling, junctional integrity, or endothelial permeability. Our results show that Rho GTPases act as mediators coupling cellular redox state to endothelial function.

scholarly journals Nrf2-AKT interactions regulate heme oxygenase 1 expression in kidney epithelia during hypoxia and hypoxia-reoxygenation

2016 ◽  
Vol 311 (5) ◽  
pp. F1025-F1034 ◽  
Author(s):  
Haranatha R. Potteti ◽  
Chandramohan R. Tamatam ◽  
Rakesh Marreddy ◽  
Narsa M. Reddy ◽  
Sanjeev Noel ◽  
...  
Keyword(s):  
Chronic Hypoxia ◽  
Ischemia Reperfusion ◽  
Acute Hypoxia ◽  
Kidney Injury ◽  
Clinical Problem ◽  
Proximal Promoter ◽  
Heme Oxygenase 1 ◽  
Antioxidant Genes ◽  
Underlying Mechanisms ◽  
Hypoxia Reoxygenation

Ischemia-reperfusion (IR)-induced kidney injury is a major clinical problem, but its underlying mechanisms remain unclear. The transcription factor known as nuclear factor, erythroid 2-like 2 (NFE2L2 or Nrf2) is crucial for protection against oxidative stress generated by pro-oxidant insults. We have previously shown that Nrf2 deficiency enhances susceptibility to IR-induced kidney injury in mice and that its upregulation is protective. Here, we examined Nrf2 target antioxidant gene expression and the mechanisms of its activation in both human and murine kidney epithelia following acute (2 h) and chronic (12 h) hypoxia and reoxygenation conditions. We found that acute hypoxia modestly stimulates and chronic hypoxia strongly stimulates Nrf2 putative target HMOX1 expression, but not that of other antioxidant genes. Inhibition of AKT1/2 or ERK1/2 signaling blocked this induction; AKT1/2 but not ERK1/2 inhibition affected Nrf2 levels in basal and acute hypoxia-reoxygenation states. Unexpectedly, chromatin immunoprecipitation assays revealed reduced levels of Nrf2 binding at the distal AB1 and SX2 enhancers and proximal promoter of HMOX1 in acute hypoxia, accompanied by diminished levels of nuclear Nrf2. In contrast, Nrf2 binding at the AB1 and SX2 enhancers significantly but differentially increased during chronic hypoxia and reoxygenation, with reaccumulation of nuclear Nrf2 levels. Small interfering-RNA-mediated Nrf2 depletion attenuated acute and chronic hypoxia-inducible HMOX1 expression, and primary Nrf2-null kidney epithelia showed reduced levels of HMOX1 induction in response to both acute and chronic hypoxia. Collectively, our data demonstrate that Nrf2 upregulates HMOX1 expression in kidney epithelia through a distinct mechanism during acute and chronic hypoxia reoxygenation, and that both AKT1/2 and ERK1/2 signaling are required for this process.

scholarly journals Tissue- and substrate-dependent mitochondrial responses to acute hypoxia-reoxygenation stress in a marine bivalve Crassostrea gigas (Thunberg, 1793)

2021 ◽  
Author(s):  
Linda Adzigbli ◽  
Eugene P. Sokolov ◽  
Siriluck Ponsuksili ◽  
Inna M. Sokolova
Keyword(s):  
Digestive Gland ◽  
Crassostrea Gigas ◽  
Acute Hypoxia ◽  
Aquatic Organisms ◽  
Acid Oxidation ◽  
Ros Generation ◽  
Marine Bivalve ◽  
Ros Production ◽  
Succinate Oxidation ◽  
Hypoxia Reoxygenation

Hypoxia is a major stressor for aquatic organisms, yet intertidal organisms like the oyster Crassostrea gigas are adapted to frequent oxygen fluctuations by metabolically adjusting to shifts in oxygen and substrate availability during hypoxia-reoxygenation (H/R). We investigated the effects of acute H/R stress (15 min at ∼0% O2, and 10 min reoxygenation) on isolated mitochondria from the gill and the digestive gland of C. gigas respiring on different substrates (pyruvate, glutamate, succinate, palmitate and their mixtures). Gill mitochondria showed better capacity for amino acid and fatty acid oxidation compared to the mitochondria from the digestive gland. Mitochondrial responses to H/R stress strongly depended on the substrate and the activity state of mitochondria. In mitochondria oxidizing NADH-linked substrates exposure to H/R stress suppressed oxygen consumption and ROS generation in the resting state, whereas in the ADP-stimulated state, ROS production increased despite little change in respiration. As a result, electron leak (measured as H2O2 to O2 ratio) increased after H/R stress in the ADP-stimulated mitochondria with NADH-linked substrates. In contrast, H/R exposure stimulated succinate-driven respiration without an increase in electron leak. Reverse electron transport (RET) did not significantly contribute to succinate-driven ROS production in oyster mitochondria except for a slight increase in the OXPHOS state during post-hypoxic recovery. A decrease in NADH-driven respiration and ROS production, enhanced capacity for succinate oxidation and resistance to RET might assist in post-hypoxic recovery of oysters mitigating oxidative stress and supporting rapid ATP re-synthesis during oxygen fluctuations such as commonly observed in estuaries and intertidal zones.

INTERACTION OF OXYGEN-SENSING MECHANISMS IN CELLS

2019 ◽  
pp. 52-62 ◽  
Author(s):  
A.N. Vetosh
Keyword(s):  
Potassium Channels ◽  
Human Body ◽  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Chronic Hypoxia ◽  
Oxygen Sensing ◽  
Acute Hypoxia ◽  
Cell Responses ◽  
Pubmed Database ◽  
In Cells

Reactions of the human body to chronic, acute or interval hypoxic hypoxia are different and may be triggered by certain intracellular molecular mechanisms. The authors analyzed PubMed database using the keywords “intracellular oxygen sensing” to verify the assumption. In 1977–2019, almost 1000 papers were published on the issue including more than 50 reviews. For their analysis, the authors chose articles on molecular oxygen sensing Metazoan tissue cells, mainly animals. Cell responses to chronic hypoxia are determined by HIF-pool localized in the cytoplasm. Oxygen-sensing to acute hypoxia in cells is preconditioned by molecular mechanisms involving potassium channels of plasma cell membranes and associated juxtamembrane complexes. Molecular intracellular reactions to interval hypoxia are triggered by the prooxidant process activation in the mitochondria of cells. This review discusses the interactional characteristics of the three mechanisms of oxygen-sensing cells. Keywords: oxygen, HIF, potassium channels of plasma membranes, mitochondria, ROS. Реакции организма человека на хроническую, острую или интервальную гипоксическую гипоксию различны и, возможно, запускаются отдельными внутриклеточными молекулярными механизмами. Для проверки этого предположения был проведён анализ литературных данных базы PubMed по ключевым словам «intracellular oxygen sensing». За период 1977–2019 гг. по данному вопросу было опубликовано почти 1000 работ, среди которых более 50 обзоров. Для анализа выбирались публикации, касающиеся молекулярной чувствительности к кислороду клеток тахитрофных тканей Metazoa, по преимуществу животных. Реакции клеток на хроническую гипоксию определяются HIF-пулом, локализованным в их цитоплазме. Кислородная чувствительность клеток к острой гипоксии обусловлена молекулярными механизмами при участии калиевых каналов плазматических клеточных мембран и ассоциированных с ними околомембранных комплексов. Молекулярные внутриклеточные реакции на интервальную гипоксию запускаются путём активизации прооксидантных процессов в митохондриях клеток. В данном обзоре обсуждаются особенности взаимодействия этих трёх механизмов кислородной чувствительности клеток. Ключевые слова: кислород, HIF, калиевые каналы плазматических мембран, митохондрии, АФК.

Zinc Dyshomeostasis in Cardiomyocytes after Acute Hypoxia/Reoxygenation

2017 ◽  
Vol 179 (1) ◽  
pp. 117-129 ◽  
Author(s):  
Vijaya Lakshmi Bodiga ◽  
Sandhya Thokala ◽  
Sita Mahalaxmi Kovur ◽  
Sreedhar Bodiga
Keyword(s):  
Acute Hypoxia ◽  
Hypoxia Reoxygenation

scholarly journals A mitochondrial electron transport chain with atypical subunit composition confers oxygen sensitivity to a mammalian chemoreceptor

2021 ◽  
Author(s):  
Alba Timon-Gomez ◽  
Alexandra L Scharr ◽  
Nicholas Y Wong ◽  
Erwin Ni ◽  
Arijit Roy ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Oxygen Sensing ◽  
Acute Hypoxia ◽  
Physiological Adaptation ◽  
Mitochondrial Electron Transport Chain ◽  
Glomus Cells ◽  
Transport Chain

The carotid body (CB) is the major chemoreceptor for blood oxygen in the control of ventilation in mammals, contributing to physiological adaptation to high altitude, pregnancy, and exercise, and its hyperactivity is linked to chronic conditions such as sleep-disorder breathing, hypertension, chronic heart failure, airway constriction, and metabolic syndrome. Upon acute hypoxia (PO2=100 mmHg to <80 mmHg), K+ channels on CB glomus cells are inhibited, causing membrane depolarization to trigger Ca+2 influx and neurotransmitter release that stimulates afferent nerves. A longstanding model proposes that the CB senses hypoxia through atypical mitochondrial electron transport chain (ETC) metabolism that is more sensitive to decreases in oxygen than other tissues. This model is supported by observations that ETC inhibition by pharmacology and gene knockout activates CB sensory activity and that smaller decreases in oxygen concentration inhibit ETC activity in CB cells compared to other cells. Determining the composition of atypical ETC subunits in the CB and their specific activities is essential to delineate molecular mechanisms underlying the mitochondrial hypothesis of oxygen sensing. Here, we identify HIGD1C, a novel hypoxia inducible gene domain factor isoform, as an ETC Complex IV (CIV) protein highly and selectively expressed in glomus cells that mediates acute oxygen sensing by the CB. We demonstrate that HIGD1C negatively regulates oxygen consumption by CIV and acts with the hypoxia-induced CIV subunit COX4I2 to enhance the sensitivity of CIV to hypoxia, constituting an important component of mitochondrial oxygen sensing in the CB. Determining how HIGD1C and other atypical CIV proteins expressed in the CB work together to confer exquisite oxygen sensing to the ETC will help us better understand how tissue- and condition-specific CIV subunits contribute to physiological function and disease and allow us to potentially target these proteins to treat chronic diseases characterized by CB dysfunction.

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