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Angiogenesis May 2018The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to... (Review)
Review
The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to recover from this cellular insult. Understanding the cellular pathways that mediate recovery from hypoxia is therefore critical for developing novel therapeutic approaches for cardiovascular diseases and cancer. The master regulators of oxygen homeostasis that control angiogenesis during hypoxia are hypoxia-inducible factors (HIFs). HIF-1 and HIF-2 function as transcriptional regulators and have both unique and overlapping target genes, whereas the role of HIF-3 is less clear. HIF-1 governs the acute adaptation to hypoxia, whereas HIF-2 and HIF-3 expressions begin during chronic hypoxia in human endothelium. When HIF-1 levels decline, HIF-2 and HIF-3 increase. This switch from HIF-1 to HIF-2 and HIF-3 signaling is required in order to adapt the endothelium to prolonged hypoxia. During prolonged hypoxia, the HIF-1 levels and activity are reduced, despite the lack of oxygen-dependent protein degradation. Although numerous protein factors have been proposed to modulate the HIF pathways, their application for HIF-targeted therapy is rather limited. Recently, the miRNAs that endogenously regulate gene expression via the RNA interference (RNAi) pathway have been shown to play critical roles in the hypoxia response pathways. Furthermore, these classes of RNAs provide therapeutic possibilities to selectively target HIFs and thus modulate the HIF switch. Here, we review the significance of the microRNAs on the relationship between the HIFs under both physiological and pathophysiological conditions.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Gene Expression Regulation; Humans; Hypoxia; MicroRNAs; Signal Transduction; Transcription, Genetic
PubMed: 29383635
DOI: 10.1007/s10456-018-9600-2 -
Aging Feb 2021Extracellular vesicles (EVs) produced by anoxia-preconditioned mesenchymal stem cells (MSCs) may afford greater cardioprotection against myocardial ischemia-reperfusion...
Extracellular vesicles (EVs) produced by anoxia-preconditioned mesenchymal stem cells (MSCs) may afford greater cardioprotection against myocardial ischemia-reperfusion injury (MIRI) than EVs derived from normoxic MSCs. Here, we isolated EVs from mouse adipose-derived MSCs (ADSCs) subjected to anoxia preconditioning or normoxia and evaluated their ability to promote survival of mouse cardiomyocytes following MIRI and anoxia/reoxygenation (AR) . Injection of anoxia-preconditioned ADSC EVs (Int-EVs) reduced both infarct size and cardiomyocyte apoptosis to a greater extent than normoxic ADSC EVs (NC-EVs) in mice subjected to MIRI. Sequencing EV-associated miRNAs revealed differential upregulation of ten miRNAs predicted to bind thioredoxin-interacting protein (TXNIP), an inflammasome- and pyroptosis-related protein. We confirmed direct binding of miRNA224-5p, the most upregulated miRNA in Int-EVs, to TXNIP and asserted through western blotting and apoptosis assays a critical protective role for this miRNA against AR-induced cardiomyocyte death. Our results suggest that ischemia-reperfusion triggers TXNIP-induced inflammasome activation in cardiomyocytes, which leads to apoptosis rather than pyroptosis due to low basal levels of the pyroptosis executioner protein gasdermin D in these cells. The antiapoptotic effect of EV-associated miRNA224-5p would in turn result from TXNIP downregulation, which prevents caspase-1-mediated degradation of GATA4 and sustains the expression of Bcl-2.
Topics: Animals; Apoptosis; Extracellular Vesicles; Hypoxia; In Vitro Techniques; Mesenchymal Stem Cells; Mice; MicroRNAs; Myocardial Reperfusion Injury; Myocytes, Cardiac
PubMed: 33578393
DOI: 10.18632/aging.202611 -
Medicinal Chemistry (Shariqah (United... 2019Hyperbaric Oxygenation Therapy (HBOT) is used as an adjunctive method for multiple diseases. The method meets the routine treating and is non-invasive, as well as... (Review)
Review
Hyperbaric Oxygenation Therapy (HBOT) is used as an adjunctive method for multiple diseases. The method meets the routine treating and is non-invasive, as well as provides 100% pure oxygen (O2), which is at above-normal atmospheric pressure in a specialized chamber. It is well known that in the condition of O2 deficiency, it will induce a series of adverse events. In order to prevent the injury induced by anoxia, the capability of offering pressurized O2 by HBOT seems involuntary and significant. In recent years, HBOT displays particular therapeutic efficacy in some degree, and it is thought to be beneficial to the conditions of angiogenesis, tissue ischemia and hypoxia, nerve system disease, diabetic complications, malignancies, Carbon monoxide (CO) poisoning and chronic radiation-induced injury. Single and combination HBOT are both applied in previous studies, and the manuscript is to review the current applications and possible mechanisms of HBOT. The applicability and validity of HBOT for clinical treatment remain controversial, even though it is regarded as an adjunct to conventional medical treatment with many other clinical benefits. There also exists a negative side effect of accepting pressurized O2, such as oxidative stress injury, DNA damage, cellular metabolic, activating of coagulation, endothelial dysfunction, acute neurotoxicity and pulmonary toxicity. Then it is imperative to comprehensively consider the advantages and disadvantages of HBOT in order to obtain a satisfying therapeutic outcome.
Topics: Animals; Cardiovascular Diseases; Humans; Hyperbaric Oxygenation; Hypoxia; Ischemia; Neovascularization, Physiologic; Nervous System Diseases
PubMed: 30569869
DOI: 10.2174/1573406415666181219101328 -
Seminars in Nephrology Nov 2019
Topics: Animals; Disease Progression; Humans; Hypoxia; Kidney; Kidney Diseases
PubMed: 31836034
DOI: 10.1016/j.semnephrol.2019.10.001 -
Cryobiology Mar 2023The wood frog, Rana sylvatica (aka Lithobates sylvaticus) is the main model for studies of natural freeze tolerance among amphibians living in seasonally cold climates....
The wood frog, Rana sylvatica (aka Lithobates sylvaticus) is the main model for studies of natural freeze tolerance among amphibians living in seasonally cold climates. During freezing, ∼65% of total body water can be converted to extracellular ice and this imposes both dehydration and hypoxia/anoxia stresses on cells. The current study analyzed the responses of the alpha subunit of the hypoxia-inducible transcription factor (HIF-1), a crucial oxygen-sensitive regulator of gene expression, to freezing, anoxia or dehydration stresses, examining six tissues of wood frogs (liver, skeletal muscle, brain, heart, kidney, skin). RT-PCR revealed a rapid elevation hif-1α transcript levels within 2 h of freeze initiation in both liver and brain and elevated levels of both mRNA and protein in liver and muscle after 24 h frozen. However, both transcript and protein levels reverted to control values after thawing except for HIF-1 protein in liver that dropped to ∼60% of control. Independent exposures of wood frogs to anoxia or dehydration stresses (two components of freezing) also triggered upregulation of hif-1α transcripts and/or HIF-1α protein in liver and kidney with variable responses in other tissues. The results show active modulation of HIF-1 in response to freezing, anoxia and dehydration stresses and implicate this transcription factor as a contributor to the regulation of metabolic adaptations needed for long term survival of wood frogs in the ischemic frozen state.
Topics: Animals; Freezing; Dehydration; Cryopreservation; Hypoxia; Ranidae; Muscle, Skeletal; Transcription Factors
PubMed: 36442660
DOI: 10.1016/j.cryobiol.2022.11.242 -
Bulletin of the World Health... Dec 2014To evaluate the cost-effectiveness of pulse oximetry--compared with no peri-operative monitoring--during surgery in low-income countries. (Comparative Study)
Comparative Study Review
OBJECTIVE
To evaluate the cost-effectiveness of pulse oximetry--compared with no peri-operative monitoring--during surgery in low-income countries.
METHODS
We considered the use of tabletop and portable, hand-held pulse oximeters among patients of any age undergoing major surgery in low-income countries. From earlier studies we obtained baseline mortality and the effectiveness of pulse oximeters to reduce mortality. We considered the direct costs of purchasing and maintaining pulse oximeters as well as the cost of supplementary oxygen used to treat hypoxic episodes identified by oximetry. Health benefits were measured in disability-adjusted life-years (DALYs) averted and benefits and costs were both discounted at 3% per year. We used recommended cost-effectiveness thresholds--both absolute and relative to gross domestic product (GDP) per capita--to assess if pulse oximetry is a cost-effective health intervention. To test the robustness of our results we performed sensitivity analyses.
FINDINGS
In 2013 prices, tabletop and hand-held oximeters were found to have annual costs of 310 and 95 United States dollars (US$), respectively. Assuming the two types of oximeter have identical effectiveness, a single oximeter used for 22 procedures per week averted 0.83 DALYs per annum. The tabletop and hand-held oximeters cost US$ 374 and US$ 115 per DALY averted, respectively. For any country with a GDP per capita above US$ 677 the hand-held oximeter was found to be cost-effective if it prevented just 1.7% of anaesthetic-related deaths or 0.3% of peri-operative mortality.
CONCLUSION
Pulse oximetry is a cost-effective intervention for low-income settings.
Topics: Cost-Benefit Analysis; Developing Countries; Female; Humans; Hypoxia; Male; Oximetry; Perioperative Care; Poverty; Quality-Adjusted Life Years
PubMed: 25552770
DOI: 10.2471/BLT.14.137315 -
Food Chemistry Mar 2022This study investigated the dynamic changes in the anaerobic metabolism end products (ethanol, acetaldehyde and ethyl acetate) of different apple cultivars during...
This study investigated the dynamic changes in the anaerobic metabolism end products (ethanol, acetaldehyde and ethyl acetate) of different apple cultivars during 84-days of regular air (RA) and controlled atmosphere (CA) storage after 0-, 3-, 7- and 14-days of anoxia. Increasing the length of exposure to anoxia increased the anaerobic metabolites concentrations (AMC) in all cultivars. Fruit could recover from anoxia, and the AMC dissipated after 84-days of storage under both storage systems when the duration of anoxia was <7-days. The rate of metabolite dissipation following 14-days of anoxia differed among cultivars and storage systems. The reduction in AMC was faster under CA than RA-storage for 'Golden Delicious' and 'Jonagold' fruit, while the opposite trend was observed for 'Kanzi'. These results indicate that storage under CA post anoxia maintains better fruit quality during 84-days of storage than RA and effectively reduces the AMC.
Topics: Anaerobiosis; Atmosphere; Fruit; Hypoxia; Malus
PubMed: 34583177
DOI: 10.1016/j.foodchem.2021.131152 -
Biomedicine & Pharmacotherapy =... Aug 2020Hypoxia, the decline of tissue oxygen stress, plays a role in mediating cellular processes. Cardiovascular disease, relatively widespread with increased mortality, is... (Review)
Review
Hypoxia, the decline of tissue oxygen stress, plays a role in mediating cellular processes. Cardiovascular disease, relatively widespread with increased mortality, is closely correlated with oxygen homeostasis regulation. Besides, hypoxia-inducible factor-1(HIF-1) is reported to be a crucial component in regulating systemic hypoxia-induced physiological and pathological modifications like oxidative stress, damage, angiogenesis, vascular remodeling, inflammatory reaction, and metabolic remodeling. In addition, HIF1 controls the movement, proliferation, apoptosis, differentiation and activity of numerous core cells, such as cardiomyocytes, endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages. Here we review the molecular regulation of HIF-1 in cardiovascular diseases, intended to improve therapeutic approaches for clinical diagnoses. Better knowledge of the oxygen balance control and the signal mechanisms involved is important to advance the development of hypoxia-related diseases.
Topics: Animals; Cardiovascular Diseases; Cardiovascular System; Homeostasis; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Oxidative Stress; Oxygen; Reactive Oxygen Species
PubMed: 32526454
DOI: 10.1016/j.biopha.2020.110338 -
The Journal of Experimental Biology Apr 2023Just over two decades ago, Bob Boutilier published a much-cited Review in this journal on the mechanisms of cell survival in hypoxia and hypothermia. Here, we celebrate...
Just over two decades ago, Bob Boutilier published a much-cited Review in this journal on the mechanisms of cell survival in hypoxia and hypothermia. Here, we celebrate this important Review by describing how our knowledge of the mechanisms behind anoxia tolerance have progressed since 2001, including new key roles of mitochondria, something Boutilier had started exploring. Evidence now suggests that, in anoxia-tolerant brains, mitochondria initiate responses aimed at suppressing electrical activity and energy use. These responses are largely dependent on gamma-aminobutyric acid (GABA) release. Animals that survive anoxia must also tolerate reoxygenation - a major challenge that could cause a massive production of damaging reactive oxygen species (ROS). Here, the handling of succinate, which builds up during anoxia, is critical. Interestingly, there are clear species differences in succinate handling among anoxia-tolerant vertebrates (Trachemys and Chrysemys turtles and crucian carp, Carassius carassius). Trachemys turtles suppress succinate build-up during anoxia, presumably to limit ROS production during reoxygenation. By contrast, in crucian carp, reduction of fumarate to succinate during anoxia appears to be essential for keeping their mitochondria charged and viable. Consequently, during anoxia, crucian carp accumulate much more succinate than Trachemys turtles. Moreover, during anoxia, succinate is apparently transported from crucian carp brain and heart to the liver, which handles succinate upon reoxygenation. This is one example of the striking physiological diversity among vertebrates that survive long-term anoxia. More examples are given, and we argue that -omics approaches are, and will be, helpful in providing new insight and moving the field forward.
Topics: Animals; Reactive Oxygen Species; Hypoxia; Brain; Vertebrates; Mitochondria; Succinic Acid; Succinates
PubMed: 37042631
DOI: 10.1242/jeb.245584 -
Journal of Experimental Zoology. Part... Apr 2023Freeze tolerance is an adaptive strategy that wood frogs (Rana sylvatica) use to survive the subzero temperatures of winter. It is characterized by a variety of...
Freeze tolerance is an adaptive strategy that wood frogs (Rana sylvatica) use to survive the subzero temperatures of winter. It is characterized by a variety of metabolic and physiological changes that facilitate successful freezing and anoxia. As both mRNA regulation and posttranslation protein modification have been implicated in freeze tolerance, we hypothesized that posttranslational RNA regulation is also involved in coordinating freeze-thaw cycles and metabolic rate depression. As such, we investigated the most abundant RNA modification, adenosine methylation (N -methyladenosine; m A) in wood frog brains during 24 h periods of freezing and anoxia. This was followed by an examination of levels of RNA methyltransferases, demethyltransferases, and the readers of RNA methylation. Despite relative levels of methylation on mRNA remaining constant throughout freezing and anoxia, a significant increase in relative abundance of m A methyltransferases METTL3 and METTL14 was observed. In addition, we investigated the effect of m A RNA methylation on mRNA triaging to stress granules and report a significant increase in stress granule markers TIAR and TIA-1 in both freezing and anoxia. Our findings are the first report of RNA posttranslational regulation during metabolic rate depression in the wood frog brain and suggest that the dynamic RNA methylation observed is not directly linked to mRNA regulation during periods of extreme metabolic reorganization, warranting future investigations.
Topics: Animals; RNA, Messenger; Freezing; Methylation; Ranidae; Hypoxia; RNA; Brain; Methyltransferases
PubMed: 36703486
DOI: 10.1002/jez.2681