ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
The phospholipase A2 activity of peroxiredoxin 6 modulates NADPH oxidase 2 activation via lysophosphatidic acid receptor signaling in the pulmonary endothelium and alveolar macrophages.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- Role of NADPH oxidase 2-derived reactive oxygen species in cardiac electrophysiological disorders.Channels (Austin, Tex.) · 2026Review
- Peroxiredoxin 6 Alone or in Combination with Fingolimod Ameliorates EAE.Current neuropharmacology · 2026Article
- Bone Marrow Mononuclear Cells Administration Restore Lysophosphatidic Acid (LPA) Levels and Cellular Signaling Axis in Rats Submitted to Renal Ischemia-Reperfusion.International journal of molecular sciences · 2025Article
- The mitochondrial lactate oxidation complex: endpoint for carbohydrate carbon disposal.American journal of physiology. Endocrinology and metabolism · 2025Article
- Loss of peroxiredoxin 6 alters lipid composition and distribution resulting in increased sensitivity to ferroptosis.The Biochemical journal · 2024Article
- Peroxiredoxin 6 suppresses ferroptosis in lung endothelial cells.Free radical biology & medicine · 2024Article
- The Role of Lysophospholipid Metabolites LPC and LPA in the Pathogenesis of Chronic Obstructive Pulmonary Disease.Metabolites · 2024Review
- Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals.BMC biology · 2024Article
- Decreased LPS-induced lung injury in pigs treated with a lung surfactant protein A-derived nonapeptide that inhibits peroxiredoxin 6 activity and subsequent NOX1,2 activation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Reactive oxygen species in endothelial signaling in COVID-19: Protective role of the novel peptide PIP-2.PloS one · 2024Article
- Transient fluid flow improves photoimmunoconjugate delivery and photoimmunotherapy efficacy.iScience · 2023Article
- Emerging Roles of Lysophosphatidic Acid in Macrophages and Inflammatory Diseases.International journal of molecular sciences · 2023Review
- Structure, Activation, and Regulation of NOX2: At the Crossroad between the Innate Immunity and Oxidative Stress-Mediated Pathologies.Antioxidants (Basel, Switzerland) · 2023Review
- Anti-Oxidant and Pro-Oxidant Effects of Peroxiredoxin 6: A Potential Target in Respiratory Diseases.Cells · 2023Review
- The Role of Phospholipase Activity of Peroxiredoxin 6 in Its Transmembrane Transport and Protective Properties.International journal of molecular sciences · 2022Article
- Behavioral and Synaptic Phenotypes of FemaleAntioxidants (Basel, Switzerland) · 2022Article
- Comprehensive molecular and morphological resolution of blubber stratification in a deep-diving, fasting-adapted seal.Frontiers in physiology · 2022Article
- Chronic ATAmerican journal of physiology. Endocrinology and metabolism · 2021Article
- Inhibition of Peroxiredoxin 6 PLA2 Activity Decreases Oxidative Stress and the Severity of Acute Lung Injury in the Mouse Cecal Ligation and Puncture Model.Antioxidants (Basel, Switzerland) · 2021Article
- Disrupted Blood-Brain Barrier and Mitochondrial Impairment by Autotaxin-Lysophosphatidic Acid Axis in Postischemic Stroke.Journal of the American Heart Association · 2021Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Peroxiredoxin 6 (Prdx6) is essential for activation of NADPH oxidase type 2 (NOX2) in pulmonary microvascular endothelial cells (PMVECs), alveolar macrophages (AMs), and polymorphonuclear leukocytes. Angiotensin II and phorbol ester increased superoxide/H2O2 generation in PMVECs, AMs, and isolated lungs from wild-type (WT) mice, but had much less effect on cells or lungs from Prdx6-null or Prdx6-D140A-knock-in mice that lack the phospholipase A2 activity (PLA2) of Prdx6; addition of either lysophosphatidylcholine (LPC) or lysophosphatidic acid (LPA) to cells restored their oxidant generation. The generation of LPC by PMVECs required Prdx6-PLA2 We propose that Prdx6-PLA2 modulates NOX2 activation by generation of LPC that is converted to LPA by the lysophospholipase D activity of autotaxin (ATX/lysoPLD). Inhibition of lysoPLD with HA130 (cells,10 μM; lungs, 20 μM; IC50, 29 nM) decreased agonist-induced oxidant generation. LPA stimulates pathways regulated by small GTPases through binding to G-protein-coupled LPA receptors (LPARs). The LPAR blocker Ki16425 (cells, 10 μM; lungs, 25 μM; Ki, 0.34 μM) or cellular knockdown of LPAR type 1 decreased oxidant generation and blocked translocation of rac1 to plasma membrane. Thus, Prdx6-PLA2 modulates NOX2 activation through generation of LPC for conversion to LPA; binding of LPA to LPAR1 signals rac activation.-Vázquez-Medina, J. P., Dodia, C., Weng, L., Mesaros, C., Blair, I. A., Feinstein, S. I., Chatterjee, S., Fisher, A. B. The phospholipase A2 activity of peroxiredoxin 6 modulates NADPH oxidase 2 activation via lysophosphatidic acid receptor signaling in the pulmonary endothelium and alveolar macrophages.
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