Human Molecular and Physiological Responses to Hypoxia PDF Download

Author: Sandro Malacrida
Publisher: Frontiers Media SA
ISBN: 2889762122
Category : Science
Languages : en
Pages : 111

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Author: Hoi I Cheong
Publisher:
ISBN:
Category : Anoxemia
Languages : en
Pages : 106

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Book Description
Life-sustaining responses to hypoxia rely on the transcription factor, Hypoxia Inducible Factor-1 (HIF-1). Under hypoxia, HIF-1 accumulates and regulates multifaceted cellular responses. However, many underlying mechanisms of HIF-1 regulation are incompletely understood. Previous studies suggest a link between HIF-1 and beta-adrenergic receptors (ßAR). Here, we interrogated the role of ßARs in hypoxia responses by ß-blocker treatment of mice with hypoxia-inducible erythropoiesis. ß-blocker suppressed renal accumulation of HIF-1a, erythropoietin production and the generation of erythroid progenitor cells. Likewise, ß-blocker treatment of human endothelial cells attenuated HIF-1a accumulation and binding to target genes under hypoxia, and subsequent downstream gene expression. Consistently, ß-agonist increased HIF-1a accumulation in a dose- and time-dependent manner, an effect that was blocked by both ß1- and ß2-blockers, indicating a general property of this receptor class. ßAR signal transduction involves cyclic adenosine monophosphate (cAMP)-activated protein kinase A (PKA) and G protein-coupled receptor kinases (GRK). Direct activation of cAMP/ PKA pathways did not increase HIF-1a accumulation, and inhibition of PKA did not suppress HIF-1a by hypoxia. In contrast, pharmacological inhibition of GRK, or genetic mutation of ßAR that impairs GRK phosphorylation, blocked hypoxia-mediated HIF-1a accumulation. Mass spectrometry analyses revealed a unique hypoxia ßAR phosphorylation barcode different from the classical agonist. These findings identify an unknown role of ßAR in hypoxia responses. Another determinant of HIF-1 regulation is nitric oxide, a potent vasodilator. A natural experiment of genetically similar Ethiopians at high altitude (>3000 m), the Amhara and Oromo, revealed a dampened hemoglobin response in Amhara compared to Oromo. We hypothesized that Amhara highlanders offset their dampened hemoglobin response with the vascular nitric oxide response. We identified high levels of urinary nitrate and its bioactive signal molecule cyclic guanosine monophosphate (cGMP) in high-altitude Amhara, but not Oromo. Consistently, high-altitude Amhara have lower diastolic blood pressure than Oromo, an indicator of vasomotor tone. Both Amhara and Oromo maintained the amount of oxyhemoglobin at high altitudes, but the high-altitude Oromo suffered a much higher deoxyhemoglobin level. In conclusion, high-altitude Amhara offset a dampened hemoglobin response with the vasodilatory nitric oxide, whereas the Oromo mount a bigger hemoglobin response at the cost of circulating deoxyhemoglobin.

Author: Rodrigo Iturriaga
Publisher: Frontiers Media SA
ISBN: 2889638006
Category :
Languages : en
Pages : 387

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The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an important role in the genesis of several human pathologies including cardiovascular, renal, myocardial and cerebral diseases in fetal, young and adult life. Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and initiate a cascade of signals intended to produce a functional systemic response. In mammals, oxygen detection mechanisms have been extensively studied in erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons, pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing is not completely known several molecular entities have been proposed as possible oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which can induce up-regulation of different genes to cope the cellular effects related to a decrease in oxygen levels. Short-term responses to hypoxia included mainly chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to manage the low oxygen concentration while more prolonged exposures to hypoxia can elicit more sustained physiological responses including switch from aerobic to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying capacity. The focus of this research topic is to provide an up-to-date vision on the current knowledge on oxygen sensing mechanism, physiological responses to acute or chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.

Author: Robert C. Roach
Publisher: Springer
ISBN: 1489976787
Category : Medical
Languages : en
Pages : 765

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Book Description
The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypoxia. Long before ‘translational medicine’ was a catchphrase, the founders of the International Hypoxia Symposia brought together basic scientists, clinicians and physiologists to live, eat, ski, innovate and collaborate in the Canadian Rockies. This collection of reviews and abstracts is divided into six sections, each covering new and important work relevant to a broad range of researchers interested in how humans adjust to hypoxia, whether on the top of Mt. Everest or in the pulmonary or cardiology clinic at low altitude. The sections include: Epigenetic Variations in Hypoxia High Altitude Adaptation Hypoxia and Sleep Hypoxia and the Brain Molecular Oxygen Sensing Physiological Responses to Hypoxia

Author: Jon C. Kolb
Publisher: Universal-Publishers
ISBN: 1581122411
Category : Medical
Languages : en
Pages : 192

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Recently, endurance athletes and high altitude climbers have gained access to commercially available, portable normobaric hypoxic chambers. Intermittent exposures to hypoxia in these chambers may elicit adaptations similar to those observed during acclimatization to altitude. Manufactures of these systems purport that intermittent exposures may elicit adaptations similar to those observed in response to the hypoxia of high altitude, however there have been no reports in the scientific literature that ventilatory acclimatization or alterations in cerebrovascular dynamics occur following repeated episodes in the portable chambers. The main conclusions are that an intermittent normobaric hypoxic intervention, consisting of five consecutive overnight exposures to a simulated altitude of 4300m, elicits perturbations in the acute cerebrovascular and ventilatory responses to both hypoxia and hypercapnia, which are similar to changes following chronic altitude exposure. Individual variability to intermittent hypoxia may have an impact on the rate at which the process of acclimatization proceeds. The extent of physiological and symptomatic responses to intermittent hypoxia are likely to be associated with the severity of hypoxia as well as the length and number of recurrent episodes of hypoxia.

Author: Sukhamay Lahiri
Publisher: Springer
ISBN: 1461475740
Category : Medical
Languages : en
Pages : 251

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Book Description
The underlying theme of this book is the biology of oxygen. The 22 chapters cover aspects of molecular, cellular, and integrative physiological functions. A fundamental evolutionary feature of the oxygen-consuming organism is that it developed a oxygen-sensing mechanism as apart of feedback control at the levels of molecules, organelles, organs, and systems. Oxygen sensing is partic ularly expressed in certain specific cells and tissues like peripheral chemore ceptors, erythroprotein-producing cells, and vascular smooth muscle. Apart of the book is focused on the current issues of this basic question of chemosen sing. Mitrochondria as the major site for cellular oxygen consumption is a nat ural candidate for cellular oxygen sensitivity and adaptation. A section deals with this question. A perennial question concerns chronic environment al oxy gen and the organism's response and adaptation to it. This theme runs through several chapters. Because comparative physiology often provides insight into the mechanisms of environment al adaptation, a chapter on respiration of high altitude birds has been incorporated. Obviously this book gives only glimpses of the immense field of oxygen biology. The book grew out of two meetings where these subjects were discussed. These meetings were sponsored by the American Physiological Society and the Federation of American Societies for Experimental Biology. We are grateful to the FASEB Program Committee and APS publication committee for their sup port. We owe much to Ms. Anne Miller for her editorial assistance. S. L. Philadelphia N. S . C. Cleveland R. S. F.

Author: Sukhamay Lahiri
Publisher: CRC Press
ISBN: 082474845X
Category : Medical
Languages : en
Pages : 756

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Reviewing research on the molecular basis of oxygen homeostasis, this text describes the changes in intracellular signalling and gene expression that lead to physiological responses to hypoxia in unicellular, invertebrate, and mammalian species. It examines O2 sensing systems in bacteria and archaea and demonstrates interrelationships among cell pr

Author: Lei Xi
Publisher: Nova Science Pub Incorporated
ISBN: 9781622577101
Category : Medical
Languages : en
Pages : 615

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In consolidation of the most updated experimental results and perspectives from diverse research fields on a main theme - Intermittent Hypoxia, this book encompasses the structural, physiological, pathophysiological, biochemical, genetic, metabolic, and therapeutic aspects of intermittent hypoxia and provides an open forum to promote the bench-to-bed translational implications of both adaptive (beneficial) and maladaptive (detrimental) responses to intermittent hypoxia in animals and humans. Authored by 74 leading scientists from 17 countries in Asia, Europe, North America, and Oceana, the 30 chapters are grouped under 7 different sections covering the profound effects of intermittent hypoxia particularly on cardiovascular, respiratory, nervous, and skeletal muscular systems. Special attentions are paid to the protective or injurious roles played by intermittent hypoxia and their underlying cellular and molecular mechanisms in several major human diseases such as acute myocardial infarction, stroke, sleep apnea, and Parkinsons disease. Several chapters have also reviewed the use of intermittent hypoxia training for enhancing exercise performance in elite athletes. Overall, as endorsed by Professor John B. West (Member, Institute of Medicine, National Academy of Sciences of U.S.A.; Editor-in-Chief, High Altitude Medicine and Biology) through his Foreword for the book, this is the most comprehensive monograph to date on the topic of intermittent hypoxia, which can cause significant structural and functional impact on the systemic, organic, cellular and molecular processes of human physiology and pathophysiology. Hence, this book could serve as a thorough reference for research scientists, physicians, academic faculty, graduate and medical students, athletic coaches and trainers, who are interested in enhancing their knowledge about the past, present, and future of intermittent hypoxia research and its translational applications for prevention and treatment of major diseases and improving exercise performance.

Author: Elena Loreti
Publisher: MDPI
ISBN: 3036501487
Category : Science
Languages : en
Pages : 288

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Molecular oxygen deficiency leads to altered cellular metabolism and can dramatically reduce crop productivity. Nearly all crops are negatively affected by a lack of oxygen (hypoxia) due to adverse environmental conditions such as excessive rain and soil waterlogging. Extensive efforts to fully understand how plants sense oxygen deficiency and their ability to respond using different strategies are crucial to increase hypoxia tolerance. Progress in our understanding has been significant in recent years. This topic certainly deserves more attention from the academic community; therefore, we have compiled a series of articles reflecting the advancements made thus far.

Author: Lei Xi
Publisher: Springer Science & Business Media
ISBN: 1447129067
Category : Medical
Languages : en
Pages : 310

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Book Description
Intermittent hypoxia can cause significant structural and functional impact on the systemic, organic, cellular and molecular processes of human physiology and pathophysiology. This book focuses on the most updated scientific understanding of the adaptive (beneficial) and maladaptive (detrimental) responses to intermittent hypoxia and their potential pathogenetic or prophylactic roles in the development and progression of major human diseases. This is a comprehensive monograph for clinicians, research scientists, academic faculty, postgraduate and medical students, and allied health professionals who are interested in enhancing their up-to-date knowledge of intermittent hypoxia research and its translational applications in preventing and treating major human diseases.