| First Author | Vázquez-Medina JP | Year | 2016 |
| Journal | FASEB J | Volume | 30 |
| Issue | 8 | Pages | 2885-98 |
| PubMed ID | 27178323 | Mgi Jnum | J:239571 |
| Mgi Id | MGI:5829164 | Doi | 10.1096/fj.201500146R |
| Citation | Vazquez-Medina JP, et al. (2016) The phospholipase A2 activity of peroxiredoxin 6 modulates NADPH oxidase 2 activation via lysophosphatidic acid receptor signaling in the pulmonary endothelium and alveolar macrophages. FASEB J 30(8):2885-98 |
| abstractText | 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 muM; lungs, 20 muM; 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 muM; lungs, 25 muM; Ki, 0.34 muM) 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.-Vazquez-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. |
