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Free Radical Biology & Medicine Sep 2023Reduced oxygen availability (hypoxia) can lead to cell and organ damage. Therefore, aerobic species depend on efficient mechanisms to counteract detrimental consequences... (Review)
Review
Reduced oxygen availability (hypoxia) can lead to cell and organ damage. Therefore, aerobic species depend on efficient mechanisms to counteract detrimental consequences of hypoxia. Hypoxia inducible factors (HIFs) and mitochondria are integral components of the cellular response to hypoxia and coordinate both distinct and highly intertwined adaptations. This leads to reduced dependence on oxygen, improved oxygen supply, maintained energy provision by metabolic remodeling and tapping into alternative pathways and increased resilience to hypoxic injuries. On one hand, many pathologies are associated with hypoxia and hypoxia can drive disease progression, for example in many cancer and neurological diseases. But on the other hand, controlled induction of hypoxia responses via HIFs and mitochondria can elicit profound health benefits and increase resilience. To tackle pathological hypoxia conditions or to apply health-promoting hypoxia exposures efficiently, cellular and systemic responses to hypoxia need to be well understood. Here we first summarize the well-established link between HIFs and mitochondria in orchestrating hypoxia-induced adaptations and then outline major environmental and behavioral modulators of their interaction that remain poorly understood.
Topics: Basic Helix-Loop-Helix Transcription Factors; Mitochondria; Cell Respiration; Humans; Animals; Temperature; Protein Stability; Altitude Sickness; Hypoxia; Diet; Oxygen; Environment
PubMed: 37385566
DOI: 10.1016/j.freeradbiomed.2023.06.015 -
Biochimica Et Biophysica Acta.... Apr 2020
Topics: Light-Harvesting Protein Complexes; Oxygen; Photosynthesis
PubMed: 32004503
DOI: 10.1016/j.bbabio.2020.148172 -
Seminars in Cancer Biology Dec 2023Disruption of oxygen homeostasis, resulting from an imbalance between O supply and demand during malignant proliferation, leads to the development of hypoxic tumor... (Review)
Review
Disruption of oxygen homeostasis, resulting from an imbalance between O supply and demand during malignant proliferation, leads to the development of hypoxic tumor microenvironments that promote the acquisition of aggressive cancer cell phenotypes linked to metastasis and patient mortality. In this review, the mechanistic links between tumor hypoxia and metastatic progression are presented. Current status and perspectives of targeting hypoxia signaling pathways as a strategy to halt cancer cell metastatic activities are emphasized.
Topics: Humans; Hypoxia; Tumor Hypoxia; Cell Hypoxia
PubMed: 37926346
DOI: 10.1016/j.semcancer.2023.11.001 -
Virology Journal Jul 2020The oxygen levels organ and tissue microenvironments vary depending on the distance of their vasculature from the left ventricle of the heart. For instance, the oxygen... (Review)
Review
The oxygen levels organ and tissue microenvironments vary depending on the distance of their vasculature from the left ventricle of the heart. For instance, the oxygen levels of lymph nodes and the spleen are significantly lower than that in atmospheric air. Cellular detection of oxygen and their response to low oxygen levels can exert a significant impact on virus infection. Generally, viruses that naturally infect well-oxygenated organs are less able to infect cells under hypoxic conditions. Conversely, viruses that infect organs under lower oxygen tensions thrive under hypoxic conditions. This suggests that in vitro experiments performed exclusively under atmospheric conditions ignores oxygen-induced modifications in both host and viral responses. Here, we review the mechanisms of how cells adapt to low oxygen tensions and its impact on viral infections. With growing evidence supporting the role of oxygen microenvironments in viral infections, this review highlights the importance of factoring oxygen concentrations into in vitro assay conditions. Bridging the gap between in vitro and in vivo oxygen tensions would allow for more physiologically representative insights into viral pathogenesis.
Topics: Cell Hypoxia; Humans; Oxygen; Virus Diseases; Viruses
PubMed: 32718318
DOI: 10.1186/s12985-020-01374-2 -
Cells Aug 2021Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based... (Review)
Review
Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrinsic factors that can control stem cell fate. One key factor controlling stem cell phenotype is oxygen (O). Several pieces of evidence demonstrated that the complexity of reproducing O physiological tensions and gradients in culture is responsible for defective stem cell behavior in vitro and after transplantation. This evidence is still worsened by considering that stem cells are conventionally incubated under non-physiological air O tension (21%). Therefore, the study of mechanisms and signaling activated at lower O tension, such as those existing under native microenvironments (referred to as hypoxia), represent an effective strategy to define if O is essential in preserving naïve stemness potential as well as in modulating their differentiation. Starting from this premise, the goal of the present review is to report the status of the art about the link existing between hypoxia and stemness providing insight into the factors/molecules involved, to design targeted strategies that, recapitulating naïve O signals, enable towards the therapeutic use of stem cell for tissue engineering and regenerative medicine.
Topics: Animals; Cell Differentiation; Cell Hypoxia; Humans; Oxygen; Stem Cells
PubMed: 34440930
DOI: 10.3390/cells10082161 -
The New Phytologist Jan 2021The major consequence of hypoxia is a dramatic reduction in energy production. At the onset of hypoxia, both oxygen and ATP availability decrease. Oxygen and energy... (Review)
Review
The major consequence of hypoxia is a dramatic reduction in energy production. At the onset of hypoxia, both oxygen and ATP availability decrease. Oxygen and energy sensing therefore converge to induce an adaptive response at both the transcriptional and translational levels. Oxygen sensing results in stabilization of the transcription factors that activate hypoxia-response genes, including enzymes required for efficient sugar metabolism, allowing plants to produce enough energy to ensure survival. The translation of the resulting mRNAs is mediated by SnRK1, acting as an energy sensor. However, as soon as the sugar availability decreases, a homeostatic mechanism, detecting sugar starvation, dampens the hypoxia-dependent transcription to reduce energy consumption and preserves carbon reserves for regrowth when oxygen availability is restored.
Topics: Cell Hypoxia; Hypoxia; Oxygen; Signal Transduction; Sugars; Transcription Factors
PubMed: 31733144
DOI: 10.1111/nph.16326 -
The Journal of Extra-corporeal... Mar 2020To remove gaseous microemboli (GME) using an oxygenator with an integrated arterial filter, it is recommended by some manufacturers to purge the oxygenator as an...
To remove gaseous microemboli (GME) using an oxygenator with an integrated arterial filter, it is recommended by some manufacturers to purge the oxygenator as an additional safety feature while on bypass. In this in vitro study, we evaluated whether purging of oxygenators with an integrated arterial filter is efficient in reducing GME. Five different types of commercially available contemporary oxygenators with an integrated arterial filter based on progressive filter filtration (1), cascade filtration (1), screen filtration (2), or self-venting (1) were tested for their efficiency in removing GME while keeping the purge line open or closed. A bubble counter was used for pre- and post-oxygenator GME signaling, from which the filter efficiency was computed. Freshly drawn heparinized porcine blood was used at blood flow rates of 3 and 5 L/min. Three units of each oxygenator were tested with its specific reservoir at a fixed volume level of 1,500 mL. GME load was introduced into the venous line at 1,000 mL air/min. Measurements started as soon as GME were detected by the pre-oxygenator probe and then continued for 1 minute. There was no statistically significant difference in filter efficiency between the purged and non-purged groups for specific oxygenators. At a blood flow of 3 L/min, the average filter efficiency stayed approximately invariable when comparing the non-purged and purged groups, where 89.1-88.2% indicated the largest difference between the groups. At a blood flow rate of 5 L/min, the filter efficiency changed in one screen filter group from an average of 55.7% in the non-purged group to 42.4% in the purged group. Other filter efficiencies at the blood flow rate of 5 L/min for non-purged compared with purged groups were, respectively, 98.0 vs. 98.0% (screen filtration), 88.6 vs. 85.8% (self-venting filtration), 82.8 vs. 75.5% (progressive filter filtration), and 65.4 vs. 65.1% (cascade filtration). Based on these results, purging while confronted with continuous GME challenge did not result in an increased filter efficiency.
Topics: Arteries; Cardiopulmonary Bypass; Equipment Design; Oxygenators, Membrane
PubMed: 32280141
DOI: 10.1182/ject-1900022 -
ELife Jul 2023The ability to sense and respond to changes in cellular oxygen levels is critical for aerobic organisms and requires a molecular oxygen sensor. The prototypical sensor... (Review)
Review
The ability to sense and respond to changes in cellular oxygen levels is critical for aerobic organisms and requires a molecular oxygen sensor. The prototypical sensor is the oxygen-dependent enzyme PHD: hypoxia inhibits its ability to hydroxylate the transcription factor HIF, causing HIF to accumulate and trigger the classic HIF-dependent hypoxia response. A small handful of other oxygen sensors are known, all of which are oxygen-dependent enzymes. However, hundreds of oxygen-dependent enzymes exist among aerobic organisms, raising the possibility that additional sensors remain to be discovered. This review summarizes known and potential hypoxia sensors among human O-dependent enzymes and highlights their possible roles in hypoxia-related adaptation and diseases.
Topics: Humans; Hypoxia; Oxygen; Gene Expression Regulation; Transcription Factors; Procollagen-Proline Dioxygenase; Hypoxia-Inducible Factor 1, alpha Subunit; Cell Hypoxia
PubMed: 37494095
DOI: 10.7554/eLife.87705 -
The Journal of Physiological Sciences :... Jul 2019Adequate oxygen supply by exposure to mild hyperbaric oxygen at appropriately high atmospheric pressure (1266-1317 hPa) and increased oxygen concentration (35-40%... (Review)
Review
Adequate oxygen supply by exposure to mild hyperbaric oxygen at appropriately high atmospheric pressure (1266-1317 hPa) and increased oxygen concentration (35-40% oxygen) has a possibility of improving the oxidative metabolism in cells and tissues without barotrauma and excessive production of reactive oxygen species. Therefore, metabolic syndrome and lifestyle-related diseases, including type 2 diabetes and hypertension, in rats were inhibited and/or improved by exposure to mild hyperbaric oxygen. It accelerated the growth-induced increase in oxidative capacity of the skeletal muscle in rats and inhibited the age-related decrease in oxidative capacity of the skeletal muscle in mice. A decrease in dopaminergic neurons in the substantia nigra of mice with Parkinson's disease was inhibited by exposure to mild hyperbaric oxygen. This review describes the beneficial effects of exposure to mild hyperbaric oxygen on some metabolic diseases and their perspectives.
Topics: Animals; Humans; Hyperbaric Oxygenation; Metabolic Diseases; Muscle, Skeletal; Oxidation-Reduction; Oxygen
PubMed: 31062232
DOI: 10.1007/s12576-019-00678-5 -
Experimental Biology and Medicine... Jul 2020Hypoxia contributes to tumor aggressiveness and promotes growth of many solid tumors that are often resistant to conventional therapies. In order to achieve successful... (Review)
Review
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.
Topics: Cell Hypoxia; Cell Respiration; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mitochondria; Neoplasms; Tumor Microenvironment
PubMed: 32594767
DOI: 10.1177/1535370220934038