bims-oxygme 2024-11-03 papers

bims-oxygme

Biomed News

on Oxygen metabolism

Issue of 2024–11–03
ten papers selected by
Onurkan Karabulut, Berkeley City College

Effects of Pressure, Hypoxia, and Hyperoxia on Neutrophil Granulocytes.
Unraveling the redox code to improve physiological research in human health and disease.
Exercise preconditioning mitigates Ischemia-Reperfusion injury in rats by enhancing mitochondrial respiration.
Unveiling the proteome of the fasting heart: Insights into HIF-1 pathway regulation.
Endometriosis development in relation to hypoxia: a murine model study.
Redox Homeostasis and Molecular Biomarkers in Precision Therapy for Cardiovascular Diseases.
Absence of heterosis for hypoxia tolerance in F1 hybrids of Tigriopus californicus.
Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models.
Understanding metabolic plasticity at single cell resolution.
Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction.

Biomolecules. 2024 Sep 30. pii: 1242. [Epub ahead of print]14(10):

Effects of Pressure, Hypoxia, and Hyperoxia on Neutrophil Granulocytes.

Richard F Kraus, Daniel Panter, Michael A Gruber, Stephanie Arndt, Petra Unger, Michael T Pawlik, Diane Bitzinger.

  Background: The application of normo- and hyperbaric O2 is a common therapy option in various disease patterns. Thereby, the applied O2 affects the whole body, including the blood and its components. This study investigates influences of pressure and oxygen fraction on human blood plasma, nutrient media, and the functions of neutrophil granulocytes (PMNs). Methods: Neutrophil migration, reactive oxygen species (ROS) production, and NETosis were examined by live cell imaging. The treatment of various matrices (Roswell Park Memorial Institute 1640 medium, Dulbecco's Modified Eagle's Medium, H2O, human plasma, and isolated PMNs) with hyperbaric oxygen (HBO) was performed. In addition, the expression of different neutrophil surface epitopes (CD11b, CD62L, CD66b) and the oxidative burst were investigated by flow cytometry (FACS). The application of cold atmospheric plasma (CAP) to normoxic and normobaric culture media served as a positive control. Soluble reaction products such as H2O2, reactive nitrogen species (RNS: NO2- and NO3-), and ROS-dependent dihydrorhodamine oxidation were quantified by fluoro- and colorimetric assay kits. Results: Under normobaric normoxia, PMNs migrate slower and shorter in comparison with normobaric hyper- or hypoxic conditions and hyperbaric hyperoxia. The pressure component has less effect on the migration behavior of PMNs than the O2 concentration. Individual PMN cells produce prolonged ROS at normoxic conditions. PMNs showed increased expression of CD11b in normobaric normoxia, lower expression of CD62L in normobaric normoxia, and lower expression of CD66b after HBO and CAP treatment. Treatment with CAP increased the amount of ROS and RNS in common culture media. Conclusions: Hyperbaric and normobaric O2 influences neutrophil functionality and surface epitopes in a measurable way, which may have an impact on disorders with neutrophil involvement. In the context of hyperbaric experiments, especially high amounts of H2O2 in RPMI after hyperbaric oxygen should be taken into account. Therefore, our data support a critical indication for the use of normobaric and hyperbaric oxygen and conscientious and careful handling of oxygen in everyday clinical practice.

Keywords:  diving; hyperbaric; hyperoxia; hypoxia; neutrophil; oxygen; pressure

DOI:  https://doi.org/10.3390/biom14101242
Physiol Rep. 2024 Nov;12(21): e70105

Unraveling the redox code to improve physiological research in human health and disease.

Josh Thorley.

  Redox reactions, involving electron transfer, are critical to human physiology. However, progress in understanding redox metabolism is hindered by flawed analytical methods. This review highlights emerging techniques that promise to revolutionize redox research, enhancing our comprehension of human health and disease. Oxygen, vital for aerobic metabolism, also produces reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. While historically seen as harmful, ROS at low concentrations are now recognized as key regulators of cell signaling. A balance between ROS and antioxidants, known as redox balance, is crucial, and deviations can lead to oxidative stress. Recent studies have distinguished beneficial "oxidative eustress" from harmful "oxidative distress." New techniques, such as advanced mass spectrometry and high-throughput immunoassays, offer improved accuracy in measuring redox states and oxidative damage. These advancements are pivotal for understanding redox signaling, cysteine oxidation, and their implications for disease. Looking ahead, the development of precision redox medicine could lead to better treatments for oxidative stress-related diseases and foster interventions promoting health.

Keywords:  ROS; cysteine; hydrogen peroxide; redox signaling

DOI:  https://doi.org/10.14814/phy2.70105
Neuroscience. 2024 Oct 24. pii: S0306-4522(24)00562-1. [Epub ahead of print]562 64-74

Exercise preconditioning mitigates Ischemia-Reperfusion injury in rats by enhancing mitochondrial respiration.

Runyu Liang, Xinlei Hou, Daguo Zhou, Luwen Zhu, Lili Teng, Wenjing Song, Qiang Tang.

  Cerebral ischemia and subsequent reperfusion damage are prevalent in clinical practice, linked to numerous neurodegenerative diseases. Cerebral ischemia deprives brain tissue of essential oxygen and nutrients, disrupting energy metabolism and causing cellular dysfunction. Although reperfusion theoretically aids recovery, it instead initiates complex injury responses such as oxidative stress, apoptosis, and inflammation, worsening brain damage. Recent research suggests that enhancing neuronal energy status by modulating energy metabolism pathways can effectively counter these effects. For instance, boosting mitochondrial function, improving energy provision, and decreasing harmful metabolites can mitigate oxidative stress and cellular injury. This study investigated the protective effects of exercise preconditioning against ischemia-reperfusion injury in rats. It was observed that exercise enhances energy levels and mitochondrial respiration by upregulating the expression of COX4 and NAMPT proteins and activating AMPK and mitochondrial complex V. This process facilitates metabolic reprogramming characterized by the promotion of oxidative phosphorylation (OXPHOS) and the pentose phosphate pathway (PPP), alongside a reduction in glycolysis. Such reprogramming reduces harmful metabolites, mitigating apoptosis and oxidative stress, and is a key factor in alleviating acute ischemic hypoxia-induced brain damage. These findings introduce a novel therapeutic approach for ischemic brain reperfusion injury, underscoring the crucial role of ATP production and metabolic regulation in neuroprotection.

Keywords:  Apoptosis; Cerebral Ischemia/Reperfusion; Exercise preconditioning; Metabolic reprogramming; Oxidative stress

DOI:  https://doi.org/10.1016/j.neuroscience.2024.10.045
Front Physiol. 2024 ;15 1462014

Unveiling the proteome of the fasting heart: Insights into HIF-1 pathway regulation.

Daniel Benak, Kristyna Holzerova, Frantisek Kolar, Miloslava Chalupova, Marketa Hlavackova.

  Fasting is a common dietary intervention known for its protective effects against metabolic and cardiovascular diseases. While its effects are mostly systemic, understanding tissue-specific changes in the heart is crucial for the identification of the mechanisms underlying fasting-induced cardioprotection. In this study, we performed a proteomic analysis of the fasting heart and attempted to clarify the molecular basis of fasting-induced cardioprotection. Our investigation identified a total of 4,652 proteins, with 127 exhibiting downregulation and 118 showing upregulation after fasting. Annotation analysis highlighted significant changes in processes such as lipid metabolism, the peroxisome pathway, and reactive oxygen species metabolism. Notably, the HIF-1 signaling pathway emerged as one of the focal points, with various HIF-1 targets exhibiting differential responses to fasting. Further experiments demonstrated downregulation of HIF-1α at both transcript and protein levels. Intriguingly, while gene expression of Egln3 decreased, its protein product PHD3 remained unaffected by fasting. The unchanged levels of pro-inflammatory cytokines indicated that the observed reduction in Hif1a expression did not stem from a decrease in basal inflammation. These findings underscore the complex regulation of the well-established cardioprotective HIF-1 signaling within the heart during 3-day fasting.

Keywords:  HIF-1; PHD3; fasting; heart; proteome

DOI:  https://doi.org/10.3389/fphys.2024.1462014
Mol Med. 2024 Oct 30. 30(1): 195

Endometriosis development in relation to hypoxia: a murine model study.

Marta Hoffmann-Młodzianowska, Radosław B Maksym, Katarzyna Pucia, Monika Kuciak, Andrzej Mackiewicz, Claudine Kieda.

   BACKGROUND: Endometriosis, due to its ambiguous symptoms, still remains one of the most difficult female diseases to treat, with an average diagnosis time of 7-9 years. The changing level of hypoxia plays an important role in a healthy endometrium during menstruation and an elevated expression of the hypoxia-inducible factor 1-alpha (HIF-1α) has been demonstrated in ectopic endometria. HIF-1α mediates the induction of proangiogenic factors and the development of angiogenesis is a critical step in the establishment and pathogenesis of endometriosis. Although the inhibition of angiogenesis has been proposed as one of the actionable therapeutic modalities, vascular normalization and re-oxygenation may become a possible new approach for therapeutic intervention.
METHODS: Our goal was to investigate whether a selected murine model of endometriosis would be suitable for future studies on new methods for treating endometriosis. Non-invasive, high-resolution ultrasound-monitored observation was selected as the preclinical approach to obtain imaging of the presence and volume of the endometriotic-like lesions. The EF5 (2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide) compound that selectively binds to reduced proteins in hypoxic cells was used for hypoxia detection. The expression of Pten and other crucial genes linking endometriosis and hypoxia were also assessed.
RESULTS: Using EF5, a pentafluorinated derivative of the 2-nitroimidazole that is metabolically reduced by oxygen-inhibitable nitroreductase, we confirmed that hypoxia did develop in the selected model and was detected in uterine and ectopic endometriotic lesions. Moreover, the changes in oxygen tension also influenced the expression level of significant genes related to endometriosis, like Pten, Trp53, Hif1a, Epas1, and Vegfa. Their strong modulation evidenced here is indicative of model reliability. Using high-resolution ultrasound-based imaging, we present a non-invasive method of visualization that enables the detection and observation of lesion evolution throughout the duration of the experiment, which is fundamental for further preclinical studies and treatment evaluation.
CONCLUSIONS: The selected model and method of visualization appear to be suitable for the study of new treatment strategies based on hypoxia alleviation and blood flow restoration.

Keywords:  EF5; Endometriosis; High-resolution ultrasound; Hypoxia; Murine model of endometriosis; PTEN

DOI:  https://doi.org/10.1186/s10020-024-00973-x
Antioxidants (Basel). 2024 Sep 25. pii: 1163. [Epub ahead of print]13(10):

Redox Homeostasis and Molecular Biomarkers in Precision Therapy for Cardiovascular Diseases.

Cristina Manuela Drăgoi, Camelia Cristina Diaconu, Alina Crenguța Nicolae, Ion-Bogdan Dumitrescu.

  Precision medicine is envisioned as the future of cardiovascular healthcare, offering a more tailored and effective method for managing cardiovascular diseases compared to the traditional one-size-fits-all approaches. The complex role of oxidative stress in chronic diseases within the framework of precision medicine was carefully explored, delving into the cellular redox status and its critical involvement in the pathophysiological complexity of cardiovascular diseases (CVDs). The review outlines the mechanisms of reactive oxygen species generation and the function of antioxidants in maintaining redox balance. It emphasizes the elevated reactive oxygen species concentrations observed in heart failure and their detrimental impact on cardiovascular health. Various sources of ROS within the cardiovascular system are examined, including mitochondrial dysfunction, which contributes to oxidative stress and mitochondrial DNA degradation. The article also addresses oxidative stress's role in myocardial remodeling, a process pivotal to the progression of heart diseases. By integrating these aspects, the review underscores the importance of redox homeostasis and identifies molecular biomarkers that can enhance precision therapy for CVDs. The insights provided aim to pave the way for targeted therapeutic strategies that mitigate oxidative stress, thereby improving patient outcomes in cardiovascular medicine.

Keywords:  cardiovascular system; heart failure; mitochondrial dysfunction; oxidative stress; precision medicine; redox homeostasis

DOI:  https://doi.org/10.3390/antiox13101163
J Hered. 2024 Oct 28. pii: esae061. [Epub ahead of print]

Absence of heterosis for hypoxia tolerance in F1 hybrids of Tigriopus californicus.

Aimee Deconinck, Olivia Madalone, Chris Willett.

Hybridization produces a range of outcomes from advantageous to disadvantageous, and a goal of genetic research is to understand the gene interactions that generate these outcomes. Interactions between cytoplasmic elements, such as mitochondria, and the nucleus may be particularly vulnerable to accruing disadvantageous combinations as a result of their different rates of evolution. However, mitonuclear incompatibilities often do not have an observable effect until the F2 and later generations. We used Tigriopus californicus, a model system for mitonuclear incompatibilities that is also known for exhibiting heterosis in the F1 generation, to test whether hypoxia was more stressful for mitonuclear interactions than other environmental stressors. We generated 284 parental and 436 F1 hybrids from four population crosses (720 total) and compared parental and F1 populations for hypoxia tolerance. We observed that, on average, F1 hybrids were less likely to survive a hypoxia stress test than parental populations (Parental:F1 coefficients ranged from -0.04 to 0.14 with none significantly different from 0). This suggests that hypoxia may be a particularly intense stressor for mitonuclear coordination, and that hybridization outcomes vary by trait.

DOI: https://doi.org/10.1093/jhered/esae061
Clin Transl Radiat Oncol. 2024 Nov;49 100875

Inhibition of OXPHOS induces metabolic rewiring and reduces hypoxia in murine tumor models.

Daan F Boreel, Anne P M Beerkens, Sandra Heskamp, Milou Boswinkel, Johannes P W Peters, Gosse J Adema, Paul N Span, Johan Bussink.

   Introduction: Tumor hypoxia is a feature of many solid malignancies and is known to cause radio resistance. In recent years it has become clear that hypoxic tumor regions also foster an immunosuppressive phenotype and are involved in immunotherapy resistance. It has been proposed that reducing the tumors' oxygen consumption will result in an increased oxygen concentration in the tissue and improve radio- and immunotherapy efficacy. The aim of this study is to investigate the metabolic rewiring of cancer cells by pharmacological attenuation of oxidative phosphorylation (OXPHOS) and subsequently reduce tumor hypoxia.
Material and methods: The metabolic effects of three OXPHOS inhibitors IACS-010759, atovaquone and metformin were explored by measuring oxygen consumption rate, extra cellular acidification rate, and [18F]FDG uptake in 2D and 3D cell culture. Tumor cell growth in 2D cell culture and hypoxia in 3D cell culture were analyzed by live cell imaging. Tumor hypoxia and [18F]FDG uptake in vivo following treatment with IACS-010759 was determined by immunohistochemistry and ex vivo biodistribution respectively.
Results: In vitro experiments show that tumor cell metabolism is heterogeneous between different models. Upon OXPHOS inhibition, metabolism shifts from oxygen consumption through OXPHOS towards glycolysis, indicated by increased acidification and glucose uptake. Inhibition of OXPHOS by IACS-010759 treatment reduced diffusion limited tumor hypoxia in both 3D cell culture and in vivo. Although immune cell presence was lower in hypoxic areas compared with normoxic areas, it is not altered following short term OXPHOS inhibition.
Discussion: These results show that inhibition of OXPHOS causes a metabolic shift from OXPHOS towards increased glycolysis in 2D and 3D cell culture. Moreover, inhibition of OXPHOS reduces diffusion limited hypoxia in 3D cell culture and murine tumor models. Reduced hypoxia by OXPHOS inhibition might enhance therapy efficacy in future studies. However, caution is warranted as systemic metabolic rewiring can cause adverse effects.

Keywords:  Atovaquone; Hypoxia; IACS-010759; Metabolism; Metformin; OXPHOS

DOI:  https://doi.org/10.1016/j.ctro.2024.100875
Essays Biochem. 2024 Oct 28. pii: EBC20240002. [Epub ahead of print]

Understanding metabolic plasticity at single cell resolution.

Christina C Abbate, Jason Hu, John G Albeck.

  It is increasingly clear that cellular metabolic function varies not just between cells of different tissues, but also within tissues and cell types. In this essay, we envision how differences in central carbon metabolism arise from multiple sources, including the cell cycle, circadian rhythms, intrinsic metabolic cycles, and others. We also discuss and compare methods that enable such variation to be detected, including single-cell metabolomics and RNA-sequencing. We pay particular attention to biosensors for AMPK and central carbon metabolites, which when used in combination with metabolic perturbations, provide clear evidence of cellular variance in metabolic function.

Keywords:  adenosine triphosphate; fluorescence resonance energy transfer; glycolysis; metabolic regulation; oxidative phosphorylation; systems biology

DOI:  https://doi.org/10.1042/EBC20240002
Sci Rep. 2024 10 30. 14(1): 26087

Menstrual cycle does not impact the hypoxic ventilatory response and acute mountain sickness prediction.

Tom Citherlet, Antoine Raberin, Giorgio Manferdelli, Vincent Pialoux, Grégoire P Millet.

  The relationship between the variations in ovarian hormones (i.e., estrogens and progesterone) and the hypoxic ventilatory response (HVR) remains unclear. HVR is a key adaptive mechanism to high altitude and has been proposed as a predictor for acute mountain sickness (AMS). This study aimed to explore the effects of hormonal changes across the menstrual cycle on HVR. Additionally, it assessed the predictive capacity of HVR for AMS and examined whether a particular menstrual phase could enhance its predictive accuracy. Thirteen eumenorrheic women performed a pure nitrogen breathing test near sea level, measuring HVR and cerebral oxygenation in early follicular, late follicular, and mid-luteal phases. Oxidative stress and ovarian hormone levels were also measured. AMS symptoms were evaluated after spending 14 h, including one overnight, at an altitude of 3,375 m. No differences in HVR, ventilation, peripheral oxygen saturation, or cerebral oxygenation were observed between the three menstrual cycle phases. Moreover, these parameters and the oxidative stress markers did not differ between the women with or without AMS (31% vs 69%), regardless of the menstrual cycle phase. In conclusion, ventilatory responses and cerebral oxygenation in normobaric hypoxia were consistent across the menstrual cycle. Furthermore, these parameters did not differentiate women with or without AMS.

Keywords:   [Formula: see text] ; Chemosensitivity; Estradiol; Female; Premenopausal; SpO2

DOI:  https://doi.org/10.1038/s41598-024-76404-y