bims-oxygme Biomed News
on Oxygen metabolism
Issue of 2024–12–08
eight papers selected by
Onurkan Karabulut, Berkeley City College
  1. Computational analysis of flow and transport suggests reduced oxygen levels within intracranial aneurysms, especially in individuals with sickle-cell disease.
  2. Enhancement of Mitochondrial Homeostasis: A Novel Approach to Attenuate Hypoxic Myocardial Injury.
  3. A microcontroller-based system for flexible oxygen control in laboratory experiments.
  4. Extreme altitude-induced central sleep apneas lasting more than 100 seconds in a healthy 23-year-old man.
  5. Cognitive impairments after maximal repeated breath-holding in elite breath-hold divers.
  6. Oxygen-controllable injectable hydrogel alleviates intervertebral disc degeneration by balancing extracellular matrix metabolism.
  7. Death-associated protein kinase 1 prevents hypoxia-induced metabolic shift and pulmonary arterial smooth muscle cell proliferation in PAH.
  8. Therapeutic hypoxia for mitochondrial disease via enhancement of hemoglobin affinity and inhibition of HIF-2α.
  1. J Biomech Eng. 2024 Dec 05. 1-26
    Computational analysis of flow and transport suggests reduced oxygen levels within intracranial aneurysms, especially in individuals with sickle-cell disease.
    Marisa Bazzi, Hadi Wiputra, David Wood, Victor H Barocas.
      Sickle cell disease (SCD) is a genetic condition characterized by an abundance of sickle hemoglobin in red blood cells. SCD patients are more prone to intracranial aneurysms (ICA) compared to the general population, with distinctive features such as multiple intracranial aneurysms: 66% of SCD patients with ICAs have multiples ICAs, compared to 20% in non-sickle patients. The exact mechanism behind these associations is not fully understood, but there is a hypothesized link between hypoxia and impaired synthesis of extracellular matrix, which may weaken the vessel walls, favoring aneurysm formation and rupture. SCD patients experience reduced blood oxygen levels, potentially exacerbating hypoxia in ICAs, and potentially contributing to aneurysm development and early onset in these patients. In this work, we performed a series of computational studies (Fluent) using idealized geometries to investigate the key differences in the oxygen transport and blood flow dynamics inside an aneurysm formation for sickle and non-sickle cases. We found that using SCD parameters resulted in a 14% to 68% reduction in blood flow and a 37% to 70% reduction in oxygen availability within the aneurysm, depending on the vessel curvature and the aneurysm throat diameter, due to factors including oxygen-dependent viscosity and alteration in the oxygen transport. The results indicate that depending on geometry and flow characteristics, some degree of hypoxia maybe present in aneurysm bulb and would be more severe in SCD patients. This study hopes to bring into attention the potential presence of hypoxic environment in the aneurysm bulb.
    DOI:  https://doi.org/10.1115/1.4067323
  2. Int J Med Sci. 2024 ;21(15): 2897-2911
    Enhancement of Mitochondrial Homeostasis: A Novel Approach to Attenuate Hypoxic Myocardial Injury.
    Zhijiang Guo, Yingjie Tian, Jing Gao, Bei Zhou, XiuTeng Zhou, Xing Chang, Hao Zhou.
      Cardiomyocytes are highly oxygen-dependent cells, relying on oxygen-driven oxidative phosphorylation to maintain their function. During hypoxia, mitochondrial ATP production decreases, leading to calcium overload, acidosis, and oxidative stress, which collectively trigger myocardial injury. Ischemic heart disease, caused by coronary atherosclerosis, results in myocardial ischemia and hypoxia, leading to ischemia-reperfusion (I/R) injury. Early myocardial injury is attributed to ischemia and hypoxia, but even after thrombolytic therapy, interventional surgery, or coronary artery bypass grafting (CABG) restores local blood flow and oxygen supply, myocardial reperfusion injury (I/R) may still occur. Mitochondria, often referred to as the "powerhouses" of the cell, play a crucial role in cellular energy production. In the early stages of ischemia and hypoxia, mitochondrial dysfunction disrupts mitochondrial homeostasis, causing the accumulation of unfolded or misfolded proteins in the mitochondria. This activates the mitochondrial unfolded protein response (mtUPR) and mitophagy, which work to clear damaged proteins and mitochondria, playing a key role during this period. This review focuses on mitochondrial mechanisms during the ischemic phase of ischemia-reperfusion injury, aiming to provide new theoretical foundations and potential therapeutic strategies to reduce myocardial damage.
    Keywords:  hypoxic myocardial injury; mitophagy; unfolded protein response (UPR)
    DOI:  https://doi.org/10.7150/ijms.103986
  3. J Exp Biol. 2024 Dec 04. pii: jeb.249207. [Epub ahead of print]
    A microcontroller-based system for flexible oxygen control in laboratory experiments.
    Stefan Mucha.
      Environmental control systems are important tools for experimental researchers studying animal-environment interactions. Commercial systems for measurement and regulation of environmental oxygen conditions are relatively expensive and can not always be adapted to varying experimental applications. Here, I present a low-cost and highly flexible oxygen control system using Arduino microcontrollers in combination with a commercial optical oxygen sensor. Hardware and software examples are provided for three different applications: single-setpoint, sequential, and long-term dissolved oxygen (DO) control. All tested control systems created the desired DO conditions with high accuracy and repeatability across trials. The resources provided shown here can be adapted and modified to be used in a variety of experimental contexts.
    Keywords:  Acclimation; Arduino; Dissolved oxygen; Environmental control; Hypoxia; Respiratory physiology
    DOI:  https://doi.org/10.1242/jeb.249207
  4. J Sleep Res. 2024 Dec 01. e14429
    Extreme altitude-induced central sleep apneas lasting more than 100 seconds in a healthy 23-year-old man.
    Grégory Heiniger, Arton Peci, Nicola Andrea Marchi, Geoffroy Solelhac, Théo Imler, Adrien Waeber, Brian Bradley, Gianpaolo Lecciso, Andrew Wellman, Alban Lovis, Pierre Monney, Denise Auberson, Raphael Heinzer.
      Central sleep apneas (CSA) can occur de novo at high-altitude in individuals without sleep-disordered breathing at low altitude. These apneas are usually brief, lasting only 5-15 s. This report presents the first documented case of a man experiencing extreme altitude-induced CSA lasting more than 100 s in the absence of any sleep breathing disorder in normoxia. A 23-year-old male with no pre-existing health conditions was recruited for a study examining the work of breathing during sleep at a simulated altitude of 3500 m (FiO2:13%). A lowland polysomnography was first conducted to exclude moderate to severe sleep-disordered breathing and showed an apnea-hypopnea index (AHI) of 7.6/h, an oxygen desaturation index (ODI) of 4.8/h, and a mean pulse oximetry-based oxygen saturation (SpO2) of 93.9%. During the recording in the hypoxic chamber, the participant experienced prolonged CSA lasting up to 1 min and 49 s. These apneas were associated with significant oxygen desaturations (nadir: 44%). To investigate the origin of these atypical CSA, the participant underwent a new low-altitude polysomnography with transcutaneous CO2 measurement (mean PaCO2:46 mmHg) and diurnal arterial blood gas analysis (pH: 7.42, pCO2: 35.1 mmHg, pO2: 79.9 mmHg, HCO3 -: 22.4 mmol/L). These results indicated no signs of chronic hypercapnia or hypocapnia. A hypoxia tolerance test (FiO2: 11.5%) demonstrated a good ventilatory response to hypoxia during exercise (1.004 L/min/kg). A rebreathing test according to the Read protocol in hyperoxia demonstrated an impaired ventilatory response to CO2 (<0.6 L/min/mmHg). This report documents a rare form of extreme hypoxia-induced CSA, potentially caused by impaired CO2 chemoreceptor sensitivity and an increased arousal threshold.
    Keywords:  central sleep apnea; high‐altitude; hypoxia; loop gain; periodic breathing
    DOI:  https://doi.org/10.1111/jsr.14429
  5. J Sports Med Phys Fitness. 2024 Dec 02.
    Cognitive impairments after maximal repeated breath-holding in elite breath-hold divers.
    Jérémie Allinger, Patrice Gueit, Sylvane Faure, Guillaume Costalat, Frédéric Lemaitre.
       BACKGROUND: Breath-hold (BH) training over several years may result in mild but persistent neurocognitive impairment. Paradoxically, the acute effects of repeated BH generating intermittent hypoxia on neurocognitive functions are still poorly understood. Therefore, we decided to examine the impact of five-repeated maximal BH on attention, processing speed, and reasoning abilities.
    METHODS: Thirty six men separated in 3 groups (12 elite BH divers: E<inf>BHD</inf>; 12 novice BH divers: N<inf>BHD</inf>; and 12 non BH divers: CTL) performed before and after 5 maximal BHs, neuropsychological computerized tasks sensitive to hypoxia. Heart rate (HR) and peripheral oxygen saturation were recorded continuously during all tests.
    RESULTS: Immediately after the five BHs, all the participants presented lower response time on the visual reaction task. E<inf>BHD</inf> did not exhibit difference in neuropsychological performance compared to N<inf>BHD</inf> and CTL, despite enduring longer BH durations.
    CONCLUSIONS: Regardless of BHD training level, repeated maximal BH may affect certain aspects of neuropsychological performance, in particularly visual reaction times. However, elite BHDs may have developed adaptive mechanisms that allow them to maintain their neurocognitive function at levels comparable to those of less trained BHDs and CTL, even with a higher dose of hypoxia.
    DOI:  https://doi.org/10.23736/S0022-4707.24.16564-4
  6. Mater Today Bio. 2024 Dec;29 101252
    Oxygen-controllable injectable hydrogel alleviates intervertebral disc degeneration by balancing extracellular matrix metabolism.
    Jia-Jie Lu, Qi-Chen Zhang, Guang-Cheng Yuan, Tai-Wei Zhang, Yu-Kai Huang, Tao Wu, Di-Han Su, Jian Dong, Li-Bo Jiang, Xi-Lei Li.
      Nucleus pulposus (NP) cells, situated at the core of intervertebral discs, have acclimated to a hypoxic environment, orchestrating the equilibrium of extracellular matrix metabolism (ECM) under the regulatory influence of hypoxia inducible factor-1α (HIF-1α). Neovascularization and increased oxygen content pose a threat, triggering ECM degradation and intervertebral disc degeneration (IVDD). To address this, our study devised an oxygen-controllable strategy, introducing laccase into an injectable and ultrasound-responsive gelatin/agarose hydrogel. Laccase-mediated reactions were employed to deplete oxygen, establishing a hypoxic microenvironment that upregulated HIF-1α expression. The activation of hypoxia-inducible factors significantly enhanced the expression of aggrecan and collagen II, concurrently suppressing Matrix metalloproteinases (MMP13) and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS5) levels, thereby restoring the equilibrium of ECM metabolism. Simultaneously, the hydrogel facilitated the recruitment of stem cells into the NP through the controlled release of ATI2341, activating C-X-C chemokine receptor type 4 (CXCR4). Moreover, ultrasound amplification enhanced ATI2341 release, promoting the migration of NP stem cells. The hydrogel's efficacy in mitigating metabolic imbalances and inhibiting IVDD progression was substantiated in a rat puncture IVDD model through hydrogel injection into the discs. In conclusion, this hypoxia-inducible hydrogel, responsive to thermal stimuli from ultrasound, presents a promising avenue for IVDD treatment.
    Keywords:  ATI2341; HIF-1α; Hypoxia-inducing hydrogel; Intervertebral disc degeneration; Ultrasonic
    DOI:  https://doi.org/10.1016/j.mtbio.2024.101252
  7. Cell Signal. 2024 Nov 30. pii: S0898-6568(24)00502-3. [Epub ahead of print]127 111527
    Death-associated protein kinase 1 prevents hypoxia-induced metabolic shift and pulmonary arterial smooth muscle cell proliferation in PAH.
    Laura-Marie Seidel, Jana Thudium, Caroline Smith, Vandna Sapehia, Natascha Sommer, Magdalena Wujak, Norbert Weissmann, Werner Seeger, Ralph T Schermuly, Tatyana Novoyatleva.
      Pulmonary hypertension (PH) is a general term used to describe high blood pressure in the lungs from any cause. Pulmonary arterial hypertension (PAH) is a progressive, and fatal disease that causes the walls of the pulmonary arteries to tighten and stiffen. One of the major characteristics of PAH is the hyperproliferation and resistance to apoptosis of vascular cells, which trigger excessive pulmonary vascular remodeling and vasoconstriction. The death-associated protein DAP-kinase (DAPK) is a tumor suppressor and Ser/Thr protein kinase, which was previously shown to regulate the hypoxia inducible factor (HIF)-1α. Against this background, we now show that DAPK1 regulates human pulmonary arterial smooth muscle cell (hPASMC) proliferation and energy metabolism in a HIF-dependent manner. DAPK1 expression is downregulated in pulmonary vessels and PASMCs of human and experimental PH lungs. Reduced expression of DAPK1 in hypoxia and non-hypoxia PAH-PASMCs correlates with increased expression of HIF-1/2α. RNA interference-mediated depletion of DAPK1 leads to fundamental metabolic changes, including a significantly decreased rate of oxidative phosphorylation associated with enhanced expression of both HIF-1α and HIF-2α and glycolytic enzymes, as hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and an integrator between the glycolysis and citric acid cycle, pyruvate dehydrogenase kinase 1 (PDK1). DAPK1 ablation in healthy donor hPASMCs leads to an increase in proliferation, while its overexpression provides the opposite effects. Together our data indicate that DAPK1 serves as a new inhibitor of the pro-proliferative and glycolytic phenotype of PH in PASMCs acting via HIF-signaling pathway.
    Keywords:  DAPK1; HIF; Metabolic shift; Mitochondrial respiration; Proliferation; Pulmonary artery smooth muscle cells
    DOI:  https://doi.org/10.1016/j.cellsig.2024.111527
  8. J Clin Invest. 2024 Dec 02. pii: e185569. [Epub ahead of print]134(23):
    Therapeutic hypoxia for mitochondrial disease via enhancement of hemoglobin affinity and inhibition of HIF-2α.
    Hong Wang, Maria Miranda, Eizo Marutani, Paul Lichtenegger, Gregory R Wojtkiewicz, Fumito Ichinose, Vamsi K Mootha.
      
    Keywords:  Genetics; Hypoxia
    DOI:  https://doi.org/10.1172/JCI185569
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