bims-oxygme 2025-01-12 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2025–01–12
ten papers selected by
Onurkan Karabulut, Berkeley City College

Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.
Unraveling High Altitude-Induced Thromboembolic Disorders: Polycythemia or Complex Mechanisms?
Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.
A preliminary exploration of establishing a mice model of hypoxic training.
Retraction: Enriched Environment Prevents Hypobaric Hypoxia Induced Memory Impairment and Neurodegeneration: Role of BDNF/PI3K/GSK3β Pathway Coupled with CREB Activation.
Oxygen is toxic in the cold in C. elegans.
Curcumin reverses cognitive deficits through promoting neurogenesis and synapse plasticity via the upregulation of PSD95 and BDNF in mice.
A New Oxygen Carrier for Therapeutic Applications.
The effect of carbohydrates with different levels of digestibility on energy metabolism in vivo under hypobaric hypoxic conditions.
LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.

Int J Mol Sci. 2024 Dec 12. pii: 13342. [Epub ahead of print]25(24):

Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.

Oleg Vetrovoy, Sofiya Potapova, Viktor Stratilov, Ekaterina Tyulkova.

  Prenatal hypoxia, often accompanied by maternal glucocorticoid stress, can predispose offspring to neurological disorders in adulthood. If placental ischemia (PI) primarily reduces fetal oxygen supply, the maternal hypoxia (MH) model also elicits a pronounced fetal glucocorticoid exposure. Here, we compared MH and PI in rats to distinguish their unique and overlapping effects on embryonic and newborn brain development. We analyzed glucocorticoid transport into the developing brain, glucocorticoid receptor (GR) expression, and GR-dependent transcription, along with key enzymes regulating glucocorticoid metabolism in maternal (MP) and fetal placentas (FP) and in the brain. Additionally, we examined hypoxia-inducible factor 1-alpha (HIF1α) and its downstream genes, as well as glycolysis and the pentose phosphate pathway, both associated with the transport of substrates essential for glucocorticoid synthesis and degradation. Both MH and PI induced HIF1-dependent metabolic alterations, enhancing glycolysis and transiently disrupting redox homeostasis. However, only MH caused a maternal glucocorticoid surge that altered early fetal brain glucocorticoid responsiveness. Over time, these differences may lead to distinct long-term outcomes in neuronal structure and function. This work clarifies the individual contributions of hypoxic and glucocorticoid stresses to fetal brain development, suggesting that combining the MH and PI models could provide valuable insights for future investigations into the mechanisms underlying developmental brain pathologies, including non-heritable psychoneurological and neurodegenerative disorders.

Keywords:  HIF1; glucocorticoid system; glycolysis; maternal hypoxia; pentose phosphate pathway; placental ischemia

DOI:  https://doi.org/10.3390/ijms252413342
High Alt Med Biol. 2025 Jan 06.

Unraveling High Altitude-Induced Thromboembolic Disorders: Polycythemia or Complex Mechanisms?

Nikunj Kumar Kansara, Anurag Timothy, Rijesh Unnithan, Manas Chatterjee.

  Kansara, Nikunj Kumar, Anurag Timothy, Rijesh Unnithan, and Manas Chatterjee. Unraveling high altitude-induced thromboembolic disorders: polycythemia or complex mechanisms?. High Alt Med Biol. 00:00-00, 2024. Background: Thromboembolic disorders (TEDs) occurring at high altitudes due to exposure to hypoxic environments pose a significant challenge for clinicians in high-altitude area. Hypobaric hypoxia often leads to acquired erythrocytosis, which is believed to increase the incidence of thrombosis. This study aims to examine the relationship between thromboembolic events and erythrocytosis. Methodology: A prospective study was conducted, including all the patients admitted to Siachen hospital for TEDs from January 01, 2022, to December 31, 2022. Data on height, duration of the stay, hemoglobin (Hb), and packed cell volume levels at the time of admission were recorded. Results: A total of 35 cases were enrolled during the study period. The average age of the patients was 29.10 years (standard deviation: 6.06). The mean deployment height was 17,300 ft, with a range of 12,000 ft-21,600 ft. The average duration of stay was 73 days, ranging from 7 to 162 days. The mean Hb level was 18 g/dl (SD: 2.64), with a range of 12.4 g/dl-22.4 g/dl. Twenty-five cases of thrombotic events (71.4%) occurred with normal Hb levels (<17.5 mg/dl), compared with 10 cases (28.6%) with Hb levels >17.5 mg/dl. Conclusion: Prolonged stays at high altitudes and exposure to hypobaric hypoxia are major stressors. The study suggests that it is not elevated Hb levels, but rather the body's lack of an appropriate physiological response, that contributes to the development of thromboembolic events.

Keywords:  cerebral vein thrombosis; deep vein thrombosis; high altitude; hypoxia; pulmonary thromboembolism

DOI:  https://doi.org/10.1089/ham.2023.0121
Cell Mol Biol Lett. 2025 Jan 06. 30(1): 2

Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer.

Jiayi Zhang, Mingxuan Yao, Shiting Xia, Fancai Zeng, Qiuyu Liu.

  Hypoxia-inducible factors (HIFs) are essential transcription factors that orchestrate cellular responses to oxygen deprivation. HIF-1α, as an unstable subunit of HIF-1, is usually hydroxylated by prolyl hydroxylase domain enzymes under normoxic conditions, leading to ubiquitination and proteasomal degradation, thereby keeping low levels. Instead of hypoxia, sometimes even in normoxia, HIF-1α translocates into the nucleus, dimerizes with HIF-1β to generate HIF-1, and then activates genes involved in adaptive responses such as angiogenesis, metabolic reprogramming, and cellular survival, which presents new challenges and insights into its role in cellular processes. Thus, the review delves into the mechanisms by which HIF-1 maintains its stability under normoxia including but not limited to giving insights into transcriptional, translational, as well as posttranslational regulation to underscore the pivotal role of HIF-1 in cellular adaptation and malignancy. Moreover, HIF-1 is extensively involved in cancer and cardiovascular diseases and potentially serves as a bridge between them. An overview of HIF-1-related drugs that are approved or in clinical trials is summarized, highlighting their potential capacity for targeting HIF-1 in cancer and cardiovascular toxicity related to cancer treatment. The review provides a comprehensive insight into HIF-1's regulatory mechanism and paves the way for future research and therapeutic development.

Keywords:  Cancer; Cellular response; HIF-1; Mechanisms; Normoxia; Pseudohypoxia; Target therapy

DOI:  https://doi.org/10.1186/s11658-024-00682-7
Sci Rep. 2025 Jan 04. 15(1): 816

A preliminary exploration of establishing a mice model of hypoxic training.

Minglu Li, Zhijie Chen, Ziyang He, Xinjuan Zhang, Yanqiu Liu, Hui Zhou, Hang Yang, Tao Liu, Xiaochuan Wang, Ran Zhang, Jiaxing Zhang.

  Altitude training has been widely adopted. This study aimed to establish a mice model to determine the time point for achieving the best endurance at the lowland. C57BL/6 and BALB/c male mice were used to establish a mice model of hypoxic training with normoxic training mice, hypoxic mice, and normoxic mice as controls. All hypoxic mice were placed in a chamber filled with 16% O2 and N2, and hypoxic training mice were trained for two weeks. Then mice were removed from the chamber and tested at normoxic conditions weekly at the beginning of the experiment and the second, third, fourth, and sixth weeks. The tests for endurance ability include maximal aerobic speed (MAS), Rota-rod, and grip strength. In addition, the open field, visual cliff, and Y maze were used to test cognitive abilities. Body composition and lactic acid tolerance level were also measured. For BALB/c but not C57BL/6 mice were evaluated for effectively training. Based on the average MAS of all mice, mice successfully passed the training according to the procedure: the first week (32%MAS/10min, 48%MAS/10min, and 64%MAS/10min) and second week (40%MAS/10min, 56%MAS/10min, and 72%MAS/10min). Hypoxic training mice reached peak rotarod performance on the 7th day post-training (Test 3), with significant improvements compared to Test 1, 2, 4, and 5. At Test 3, their rotarod scores significantly differed from both H and N groups, and showing a trend towards difference from NT group. Meanwhile, hypoxic mice showed significant cognitive impairment, anxiety, depression, muscle loss, and fat gain compared with hypoxic training mice after hypoxia intervation. Two consecutive weeks of 16% O2 training followed by one week of reoxygenation may be the best for endurance competition. Thus, we think a mouse model for hypoxic training was built, with Rota-rod testing as a detection indicator. Moreover, hypoxic training may alleviate the damage of hypoxia to the body.

Keywords:  Behavioral tests; Cognition; High altitude training; Peak athletic performance

DOI:  https://doi.org/10.1038/s41598-024-84371-7
PLoS One. 2025 ;20(1): e0317531

Retraction: Enriched Environment Prevents Hypobaric Hypoxia Induced Memory Impairment and Neurodegeneration: Role of BDNF/PI3K/GSK3β Pathway Coupled with CREB Activation.

PLOS ONE Editors

DOI: https://doi.org/10.1371/journal.pone.0317531
Front Physiol. 2024 ;15 1471249

Oxygen is toxic in the cold in C. elegans.

Cameron M Suraci, Michael L Morrison, Mark B Roth.

   Introduction: Temperature and oxygen are two factors that profoundly affect survival limits of animals; too much or too little of either is lethal. However, humans and other animals can exhibit exceptional survival when oxygen and temperature are simultaneously low. This research investigates the role of oxygen in the cold shock death of Caenorhabditis elegans.
Methods: The survival of C. elegans populations in combinations of oxygen concentrations and was assayed. Additionally, the effect of cold acclimatization, mutations in the cold acclimatization pathway, compounds, and antioxidant proteins on survival in low temperatures and high oxygen were investigated.
Results: We demonstrate that C. elegans have increased survival in 2°C when deprived of oxygen, and an increase to just 0.25 kPa of oxygen decreased survival. Additionally, we show that oxygen toxicity produced by a 35-fold increase above atmospheric oxygen levels was fatal for nematodes in 8 h at room temperature and 2 h at 2°C. We found that cold acclimatization and mutations in the cold acclimatization pathway improve survival in room temperature oxygen toxicity. Furthermore, we found that the compounds glucose, manganese (II), and ascorbate improve both cold shock and high oxygen survival, while the antioxidant proteins catalase and peroxiredoxin are essential to wild type survival in these conditions.
Discussion: Our results suggest that oxygen toxicity contributes to the death of C. elegans during cold shock. The changes in survival induced by cold acclimatization and mutations in the cold acclimatization pathway suggest that oxygen toxicity in the cold exerts evolutionary pressure, leading to the development of protections against it. Additionally, the resistance provided by diverse compounds and antioxidant proteins in both low temperature and high oxygen suggests these conditions have similar chemical environments. We discuss evidence that similar phenomena may function in humans.

Keywords:  C. elegans; ROS; cold acclimatization; cold shock; oxidative stress; oxygen; survival; temperature

DOI:  https://doi.org/10.3389/fphys.2024.1471249
Sci Rep. 2025 Jan 07. 15(1): 1135

Curcumin reverses cognitive deficits through promoting neurogenesis and synapse plasticity via the upregulation of PSD95 and BDNF in mice.

Gaifen Li, Qiong Wu, Chao Wang, Pin Deng, Jiaxin Li, Zhiguang Zhai, Yubo Li.

  Following prolonged exposure to hypoxic conditions, for example, due to ascent to high altitude, aging or stroke, cognitive deficits can develop. The exact nature and genesis of hypoxia-induced cognitive deficits remain unresolved. Curcumin has been reported to stimulate neurogenesis and reduce neuronal degeneration. This study aimed to investigate the effect of curcumin on cognitive deficits in hypoxic-brain injury mice and its potential mechanism. Eight-week-old male C57BL/6J mice were exposure to normobaric-hypoxia (13%O2) 14 days to establish hypoxic-brain injury models. Morris water maze and novel object recognition were used to detect the cognitive function of each mouse. Immunofluorescence assays, including Fluoro-Jade C (FJC) and bromodeoxyuridine (BrdU), were used to detect neuronal degeneration and neurogenesis. Thy1-YFP transgenic mice were used to detect synapse plasticity. Our results showed that curcumin administration rescued the impaired cognition of mice, shown as enhanced BrdU+ and dendritic spine in hippocampus. At the molecular level, curcumin was found to promote the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95). The results of primary hippocampal neuron detection showed that curcumin could promote dendritic growth. In conclusion, our study indicates that curcumin, increased BDNF and PSD95 expression and contacted with interneurons, salvaged of interneurons may normalize ambient neuroplasticity, resulting in the preservation of neurogenesis processes as well as contributing to improve cognitive performance.

Keywords:  Cognitive deficits; Curcumin; Hypoxia; Neurogenesis; Synapse plasticity

DOI:  https://doi.org/10.1038/s41598-024-82571-9
Drug Test Anal. 2025 Jan 06.

A New Oxygen Carrier for Therapeutic Applications.

Benoit Barrou, Elisabeth Leize-Zal, Franck Zal.

  The natural extracellular hemoglobin of the lugworm Arenicola marina (AmHb) has many interesting characteristics: It carries 40 times more oxygen than human hemoglobin; has anti-inflammatory, antibacterial, and antioxidant properties; and is 250 times smaller than a red blood cell. It is nontoxic and nonimmunogenic. It is thus a very promising hemoglobin-based oxygen carrier. AmHb is extracted and purified in GMP conditions to produce a therapeutic molecule, called M101. It is used in various forms (liquid, hydrogel, and lyophilized) to respond to different situations of hypoxia in the healthcare field, such as organ preservation prior to transplantation, wound and burn healing, periodontitis, sickle cell disease, and red blood cell transfusions, particularly in emergency situations. Given these remarkable oxygen transport capacities, M101 could be misused for doping purposes. This article presents current and future developments in this molecule.

Keywords:  hemoglobin; hemoglobin‐based carrier; organ preservation; oxygen; wound healing

DOI:  https://doi.org/10.1002/dta.3847
Carbohydr Polym. 2025 Mar 01. pii: S0144-8617(24)01340-7. [Epub ahead of print]351 123114

The effect of carbohydrates with different levels of digestibility on energy metabolism in vivo under hypobaric hypoxic conditions.

Yali Huang, Lingjin Li, Yan Hong, Li Cheng, Zhengbiao Gu.

  Current strategies for improving energy supply in hypobaric hypoxic environments are limited. Therefore, this study investigates the effects of four carbohydrates with different levels of digestibility on energy metabolism in vivo in hypobaric hypoxic environments. First, we characterized the four types of carbohydrates. Subsequently, reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to characterize the expression of GLUT1, GLUT2, and SGLT1 in the glucose transport pathway in vivo. In addition, the effects of different levels of carbohydrate digestibility on energy expenditure were evaluated in vivo. The results showed that pre-gelatinized corn starch significantly increased GLUT1 gene expression in the hypobaric hypoxic conditions (1.58 times, compared to normobaric normoxic). In addition, pre-gelatinized corn starch increased energy expenditure in the hypobaric hypoxic conditions and performed better in terms of glycogen accumulation and glucose transport. Therefore, pre-gelatinized corn starch administration may be a promising strategy for long-term energy supplementation in hypobaric hypoxic.

Keywords:  Digestion; Energy supplement; Glycometabolism; Maize starch; Pre-gelatinized starch

DOI:  https://doi.org/10.1016/j.carbpol.2024.123114
PLoS One. 2025 ;20(1): e0314020

LFA-1: A potential key player in microglia-mediated neuroprotection against oxygen-glucose deprivation in vitro.

Robin Jansen, Marc Pawlitzki, Michael Gliem, Sven G Meuth, Stefanie Schreiber, Michael-W Görtler, Jens Neumann.

For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice. Our present study reveals the relevance of a β2 integrin, lymphocyte function-associated antigen-1 (LFA-1), as a potential key player in protecting neuronal cell death after oxygen-glucose deprivation in organotypic hippocampal cell cultures. In addition, we identified microglial cells as effector cells for LFA-1-mediated neuroprotection. The counterpart of LFA-1 on microglia is unclear, but we show strong expression of ICAM-5 in hippocampal neurons, suggesting a critical role for direct crosstalk between microglia and neurons for neuronal survival under oxygen-glucose deprivation. The enigma of neuroprotection after ischemic stroke remains to be solved, and our findings highlight the continuing importance and lack of understanding of integrin-mediated pathways after ischemic stroke and the need for further intensive research.

DOI: https://doi.org/10.1371/journal.pone.0314020