The objective of this study was to examine the impact of chronic hyperoxic exposure (95% O2 for 48 h) on intact bovine pulmonary arterial endothelial cell redox metabolism of 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ). DQ or durohydroquinone (DQH2) was added to normoxic or hyperoxia-exposed cells in air-saturated medium, and the medium DQ concentrations were measured over 30 min. DQ disappeared from the medium when DQ was added and appeared in the medium when DQH2 was added, such that after approximately 15 min, a steady-state DQ concentration was approached that was approximately 4.5 times lower for the hyperoxia-exposed than the normoxic cells. The rate of DQ-mediated reduction of the cell membrane-impermeant redox indicator, potassium ferricyanide [Fe(CN)6(3-)], was also approximately twofold faster for the hyperoxia-exposed cells. Inhibitor studies and mathematical modeling suggested that in both normoxic and hyperoxia-exposed cells, NAD(P)H:quinone oxidoreductase 1 (NQO1) was the dominant DQ reductase and mitochondrial electron transport complex III the dominant DQH2 oxidase involved and that the difference between the net effects of the cells on DQ redox status could be attributed primarily to a twofold increase in the maximum NQO1-mediated DQ reduction rate in the hyperoxia-exposed cells. Accordingly, NQO1 protein and total activity were higher in hyperoxia-exposed than normoxic cell cytosolic fractions. One outcome for hyperoxia-exposed cells was enhanced protection from cell-mediated DQ redox cycling. This study demonstrates that exposure to chronic hyperoxia increases the capacity of pulmonary arterial endothelial cells to reduce DQ to DQH2 via a hyperoxia-induced increase in NQO1 protein and total activity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1152/ajplung.00302.2005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Macrophage extracellular vesicle-packaged miR-23a-3p impairs maintenance and angiogenic capacity of human endothelial progenitor cells in neonatal hyperoxia-induced lung injury.
Stem Cell Res Ther
September 2024
Laboratory of Neonatology, Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, 518000, China.
Background: Premature infants requiring mechanical ventilation and supplemental oxygen for respiratory support are at increased risk for bronchopulmonary dysplasia (BPD), wherein inflammation have been proposed as a driver of hyperoxia-induced injuries, including persistent loss of endothelial progenitor cells (EPCs), impaired vascularization and eventual alveolar simplification in BPD lungs. However, the underlying mechanisms linking these phenomena remain poorly defined.
Methods: We used clodronate liposomes to deplete macrophages in a mouse model of neonatal hyperoxia-induced lung injury to evaluate if EPC loss in BPD lungs could be an effect of macrophage infiltration.
Role of sex as a biological variable in neonatal alveolar macrophages.
Redox Biol
September 2024
Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, University of Pennsylvania, PA, USA. Electronic address:
Article Synopsis
- Lung macrophages are important in health and disease, with their function influenced by biological sex, which can lead to different health outcomes in conditions like bronchopulmonary dysplasia (BPD).
- Research investigated how the transcriptional state of alveolar macrophages in neonatal mice is affected by hyperoxia-induced lung injury, revealing that injury reduces macrophage levels initially but allows for recovery in both sexes.
- Analysis showed that female macrophages enriched pathways related to DNA damage and interferon signaling, while male macrophages showed enriched glucose metabolism pathways; similar trends were observed in human premature neonates.
Interleukin-11 Is Involved in Hyperoxia-induced Bronchopulmonary Dysplasia in Newborn Mice by Mediating Epithelium-Fibroblast Cross-talk.
Inflammation
July 2024
Department of Neonatology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disorder predominantly affecting preterm infants. Oxygen therapy, a common treatment for BPD, often leads to hyperoxia-induced pulmonary damage, particularly targeting alveolar epithelial cells (AECs). Crucially, disrupted lung epithelium-fibroblast interactions significantly contribute to BPD's pathogenesis.
View Article and Find Full Text PDFAdipose mesenchymal stem cells-derived exosomes attenuated hyperoxia-induced lung injury in neonatal rats via inhibiting the NF-κB signaling pathway.
Pediatr Pulmonol
October 2024
Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Objective: Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in extremely preterm infants. Mesenchymal stem cells-derived exosomes (MSC-Exos) therapies have shown prospects in animal models of BPD. Our study aimed to evaluate the effect of adipose mesenchymal stem cells-derived exosomes (AMSC-Exos) on BPD and the role of the NF-κB signaling pathway in this process.
View Article and Find Full Text PDFThe chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!