scholarly journals Cardiac responses to hypoxia and reoxygenation in Drosophila

2015 ◽  
Vol 309 (11) ◽  
pp. R1347-R1357 ◽  
Author(s):  
Rachel Zarndt ◽  
Sarah Piloto ◽  
Frank L. Powell ◽  
Gabriel G. Haddad ◽  
Rolf Bodmer ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Genetic Model ◽  
Heart Function ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factor ◽  
High Energy ◽  
Hypoxic Exposure ◽  
Low Oxygen ◽  
Cardiac Responses ◽  
Organ Systems

An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-α), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation.

The Role of the Aortic Body Chemoreceptors in the Cardiac and Respiratory Responses to Acute Hypoxia in the Anesthetized Dog

1973 ◽  
Vol 51 (4) ◽  
pp. 249-259 ◽  
Author(s):  
G. P. Biro ◽  
J. D. Hatcher ◽  
D. B. Jennings
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Acute Hypoxia ◽  
Control Period ◽  
Indirect Evidence ◽  
Minute Volume ◽  
Significant Rise ◽  
Cardiac Response ◽  
Cardiac Responses ◽  
Respiratory Parameters

The participation of the aortic chemoreceptors in the reflex cardiac responses to acute hypoxia is suggested only by the indirect evidence of pharmacological stimulation of these receptors. In order to assess their role more directly, the response to a 15 min period of hypoxia was determined after surgical denervation of the aortic chemoreceptors (A.D.), and compared with the response of sham-operated (S.O.) dogs, anesthetized with morphine–pentobarbital. In the control period, while breathing room air, the cardiovascular and respiratory parameters measured in the A.D. animals were not different from those of the S.O. dogs. Hypoxia (partial pressure of oxygen approximately 30 mm Hg) in the S.O. dogs was associated with a statistically significant rise in the heart rate (+71 ± 7 min−1, mean ± S.E.M.) and of the cardiac output (+25 ± 10 ml kg−1 min−1). In the A.D. animals, the significantly smaller increment in heart rate (+29 ± 6 min−1) was associated with a fall of the cardiac output (−16 ± 12 ml kg−1 min−1). The hypoxia-induced changes in heart rate and cardiac output in the S.O. animals were different (p < 0.05) from those in the A.D. group. The minute volume of ventilation was significantly augmented in both groups, and to a comparable extent. These findings indicate that the aortic chemoreceptors play a significant role in the cardiac response to hypoxia, but they do not affect, to a significant extent, the respiratory response.

Physiology in Medicine: A physiologic approach to prevention and treatment of acute high-altitude illnesses

2015 ◽  
Vol 118 (5) ◽  
pp. 509-519 ◽  
Author(s):  
Andrew M. Luks
Keyword(s):  
High Altitude ◽  
Acute Hypoxia ◽  
Acute Mountain Sickness ◽  
Travel Medicine ◽  
Barometric Pressure ◽  
Time Frame ◽  
Low Oxygen ◽  
Organ Systems ◽  
Prevention And Treatment ◽  
Physiologic Responses

With the growing interest in adventure travel and the increasing ease and affordability of air, rail, and road-based transportation, increasing numbers of individuals are traveling to high altitude. The decline in barometric pressure and ambient oxygen tensions in this environment trigger a series of physiologic responses across organ systems and over a varying time frame that help the individual acclimatize to the low oxygen conditions but occasionally lead to maladaptive responses and one or several forms of acute altitude illness. The goal of this Physiology in Medicine article is to provide information that providers can use when counseling patients who present to primary care or travel medicine clinics seeking advice about how to prevent these problems. After discussing the primary physiologic responses to acute hypoxia from the organ to the molecular level in normal individuals, the review describes the main forms of acute altitude illness—acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema—and the basic approaches to their prevention and treatment of these problems, with an emphasis throughout on the physiologic basis for the development of these illnesses and their management.

Response of pulmonary circulation of resting, unanesthetized dogs to acute hypoxia

1964 ◽  
Vol 206 (4) ◽  
pp. 867-874 ◽  
Author(s):  
Otto G. Thilenius ◽  
Paul B. Hoffer ◽  
Robert S. Fitzgerald ◽  
John F. Perkins
Keyword(s):  
Cardiac Output ◽  
Pulmonary Artery ◽  
Left Atrium ◽  
Pulmonary Circulation ◽  
Normal Values ◽  
Acute Hypoxia ◽  
Time Sequence ◽  
Low Oxygen ◽  
Marked Rise ◽  
Vascular Bed

By means of chronically implanted vinyl catheters, pressures in aorta, pulmonary artery (PAP), left atrium (LAP), and intrapleural space (by capsule) were recorded simultaneously and continuously, together with cardiac output (Q) by dye-dilution technic every 2 min, in unanesthetized, unsedated trained dogs for 1 hr during breathing of air and low oxygen mixtures (6–15%) via a chronic tracheostomy. In nearly all of 54 experiments on 5 animals there were striking responses to hypoxia, consisting of a marked rise in PAP (up to 120%), in Q (up to 75%), in pulmonary vascular resistance (PVR) (up to 200%), and of a significant fall in LAP. In some animals these changes were not maintained throughout hypoxia. The PVR usually returned toward normal first, followed by the PAP, while Q remained elevated. The time sequence of these events varied in different animals. Effects of the same magnitude as in hypoxia accompanied restlessness caused by stress, but fluctuated markedly, were of shorter duration, and could largely be climinated by providing quiet surroundings and by avoiding prolonged experiments. It was concluded that active vasoconstriction occurs in the pulmonary vascular bed during acute hypoxia (breathing of 6–15% O2) in the intact, unanesthetized dog. Furthermore, normal values for PAP, Q, and PVR for the resting, waking dog are reported.

scholarly journals Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target

2021 ◽  
Vol 22 (11) ◽  
pp. 5703
Author(s):  
Vittoria Infantino ◽  
Anna Santarsiero ◽  
Paolo Convertini ◽  
Simona Todisco ◽  
Vito Iacobazzi
Keyword(s):  
Cancer Cells ◽  
Energy Demand ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Cancer Therapeutics ◽  
High Energy ◽  
Metabolic Reprogramming ◽  
Low Oxygen ◽  
Functional Changes

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells.

Hypoxia in the central nervous system

2007 ◽  
Vol 43 ◽  
pp. 138-152 ◽  
Author(s):  
Joseph C. LaManna
Keyword(s):  
Hypoxia Inducible Factor ◽  
Time Frame ◽  
High Energy ◽  
Low Oxygen ◽  
Adaptive Mechanisms ◽  
Oxygen Conditions ◽  
Very High Energy ◽  
The Central Nervous System ◽  
The Brain ◽  
Very High

The brain, as a very high energy consumer, is completely reliant on molecular oxygen but because oxygen is dangerous due to toxicity [1], there are mechanisms which allow the brain to exist under low oxygen conditions when ‘idling’ but increase oxygen delivery when activated. This situation means that the brain can respond naturally to mild hypoxia with acute and chronic adaptive mechanisms. These mechanisms involve systemic and central metabolic and vascular processes that are mediated by hypoxia-inducible factor (HIF)-1. HIF-1-mediated cerebral angiogenesis is completed within 3 weeks of exposure onset and is reversible over the same time frame if normoxia is restored. Hypoxic acclimatizing responses may be significantly impaired with aging and metabolic or vascular disease.

Oxygen-dependent gene expression in fishes

2005 ◽  
Vol 288 (5) ◽  
pp. R1079-R1090 ◽  
Author(s):  
Mikko Nikinmaa ◽  
Bernard B. Rees
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Hypoxia Tolerance ◽  
Hypoxic Exposure ◽  
Low Oxygen ◽  
Mammalian Development ◽  
Molecular Responses ◽  
And Function

The role of oxygen in regulating patterns of gene expression in mammalian development, physiology, and pathology has received increasing attention, especially after the discovery of the hypoxia-inducible factor (HIF), a transcription factor that has been likened to a “master switch” in the transcriptional response of mammalian cells and tissues to low oxygen. At present, considerably less is known about the molecular responses of nonmammalian vertebrates and invertebrates to hypoxic exposure. Because many animals live in aquatic habitats that are variable in oxygen tension, it is relevant to study oxygen-dependent gene expression in these animals. The purpose of this review is to discuss hypoxia-induced gene expression in fishes from an evolutionary and ecological context. Recent studies have described homologs of HIF in fish and have begun to evaluate their function. A number of physiological processes are known to be altered by hypoxic exposure of fish, although the evidence linking them to HIF is less well developed. The diversity of fish presents many opportunities to evaluate if inter- and intraspecific variation in HIF structure and function correlate with hypoxia tolerance. Furthermore, as an aquatic group, fish offer the opportunity to examine the interactions between hypoxia and other stressors, including pollutants, common in aquatic environments. It is possible, if not likely, that results obtained by studying the molecular responses of fish to hypoxia will find parallels in the oxygen-dependent responses of mammals, including humans. Moreover, novel responses to hypoxia could be discovered through studies of this diverse and species-rich group.

HIF1-α-Mediated Gene Expression Induced by Vitamin B1 Deficiency

2013 ◽  
Vol 83 (3) ◽  
pp. 188-197 ◽  
Author(s):  
Rebecca L. Sweet ◽  
Jason A. Zastre
Keyword(s):  
Gene Expression ◽  
Thiamine Deficiency ◽  
Glucose Transporter ◽  
Neuroblastoma Cell ◽  
Hypoxia Inducible Factor ◽  
Clinical Manifestations ◽  
Vitamin B1 ◽  
Low Oxygen ◽  
Glucose Transporter 1 ◽  
Metabolic Intermediates

It is well established that thiamine deficiency results in an excess of metabolic intermediates such as lactate and pyruvate, which is likely due to insufficient levels of cofactor for the function of thiamine-dependent enzymes. When in excess, both pyruvate and lactate can increase the stabilization of the hypoxia-inducible factor 1-alpha (HIF-1α) transcription factor, resulting in the trans-activation of HIF-1α regulated genes independent of low oxygen, termed pseudo-hypoxia. Therefore, the resulting dysfunction in cellular metabolism and accumulation of pyruvate and lactate during thiamine deficiency may facilitate a pseudo-hypoxic state. In order to investigate the possibility of a transcriptional relationship between hypoxia and thiamine deficiency, we measured alterations in metabolic intermediates, HIF-1α stabilization, and gene expression. We found an increase in intracellular pyruvate and extracellular lactate levels after thiamine deficiency exposure to the neuroblastoma cell line SK-N-BE. Similar to cells exposed to hypoxia, there was a corresponding increase in HIF-1α stabilization and activation of target gene expression during thiamine deficiency, including glucose transporter-1 (GLUT1), vascular endothelial growth factor (VEGF), and aldolase A. Both hypoxia and thiamine deficiency exposure resulted in an increase in the expression of the thiamine transporter SLC19A3. These results indicate thiamine deficiency induces HIF-1α-mediated gene expression similar to that observed in hypoxic stress, and may provide evidence for a central transcriptional response associated with the clinical manifestations of thiamine deficiency.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals Hypoxic tumor microenvironment: Implications for cancer therapy

2020 ◽  
Vol 245 (13) ◽  
pp. 1073-1086
Author(s):  
Sukanya Roy ◽  
Subhashree Kumaravel ◽  
Ankith Sharma ◽  
Camille L Duran ◽  
Kayla J Bayless ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Tumor Vasculature ◽  
Therapeutic Strategies ◽  
Therapeutic Resistance ◽  
Low Oxygen ◽  
Cancer Types

Hypoxia or low oxygen concentration in tumor microenvironment has widespread effects ranging from altered angiogenesis and lymphangiogenesis, tumor metabolism, growth, and therapeutic resistance in different cancer types. A large number of these effects are mediated by the transcription factor hypoxia inducible factor 1⍺ (HIF-1⍺) which is activated by hypoxia. HIF1⍺ induces glycolytic genes and reduces mitochondrial respiration rate in hypoxic tumoral regions through modulation of various cells in tumor microenvironment like cancer-associated fibroblasts. Immune evasion driven by HIF-1⍺ further contributes to enhanced survival of cancer cells. By altering drug target expression, metabolic regulation, and oxygen consumption, hypoxia leads to enhanced growth and survival of cancer cells. Tumor cells in hypoxic conditions thus attain aggressive phenotypes and become resistant to chemo- and radio- therapies resulting in higher mortality. While a number of new therapeutic strategies have succeeded in targeting hypoxia, a significant improvement of these needs a more detailed understanding of the various effects and molecular mechanisms regulated by hypoxia and its effects on modulation of the tumor vasculature. This review focuses on the chief hypoxia-driven molecular mechanisms and their impact on therapeutic resistance in tumors that drive an aggressive phenotype. Impact statement Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful therapeutic strategies targeting different cancer types, it is necessary to understand the molecular mechanisms and signaling pathways that are induced by hypoxia. Aberrant tumor vasculature and alterations in cellular metabolism and drug resistance due to hypoxia further confound this problem. This review focuses on the implications of hypoxia in an inflammatory TME and its impact on the signaling and metabolic pathways regulating growth and progression of cancer, along with changes in lymphangiogenic and angiogenic mechanisms. Finally, the overarching role of hypoxia in mediating therapeutic resistance in cancers is discussed.

scholarly journals Low oxygen delivery produced by anemia, hypoxia, and low cardiac output

1991 ◽  
Vol 51 (5) ◽  
pp. 425-433 ◽  
Author(s):  
Robert E. Cilley ◽  
Andrew M. Scharenberg ◽  
Phillip F. Bongiorno ◽  
Kenneth E. Guire ◽  
Robert H. Bartlett
Keyword(s):  
Cardiac Output ◽  
Oxygen Delivery ◽  
Low Oxygen ◽  
Low Cardiac Output
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