Peroxiredoxin 6 phospholipid hydroperoxidase activity in the repair of peroxidized cell membranes
| Autor: | Chandra Dodia, Jian-Qin Tao, Elena M. Sorokina, Sheldon I. Feinstein, Jose P. Vasquez-Medina, Aron B. Fisher |
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| Rok vydání: | 2018 |
| Předmět: |
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wild type 0301 basic medicine Male Endothelial cells Clinical Biochemistry Histidine mutation Medical Biochemistry and Metabolomics GPX4 medicine.disease_cause Inbred C57BL Perfused lung Biochemistry FOX ferrous xylenol orange Lipid peroxidation chemistry.chemical_compound Mice Null cell 2.1 Biological and endogenous factors Aetiology lcsh:QH301-705.5 Lung Cells Cultured Mice Knockout Hyperoxia lcsh:R5-920 Cultured biology PHGPx phospholipid hydroperoxide GSH peroxidase t-BOOH tert-butyl hydroperoxide PCOOH 1-palmitoyl 2-linoleoyl sn-3-glycerophosphocholine hydroperoxide GPx GSH peroxidase Prdx6 peroxiredoxin 6 PMVEC pulmonary microvascular endothelial cells Pharmacology and Pharmaceutical Sciences respiratory system Recombinant Proteins Cell Hypoxia Cell biology DPPP diphenylpyrenyl phosphate medicine.symptom lcsh:Medicine (General) Research Paper Cells Knockout Phospholipid 03 medical and health sciences Phospholipase A2 medicine Animals 030102 biochemistry & molecular biology FA fatty acid Organic Chemistry Cell Membrane Wild type Hydrogen Peroxide Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) chemistry PLOOH phospholipid hydroperoxides Microvessels LPCAT lysophosphatidylcholine acyl transferase biology.protein Biochemistry and Cell Biology Oxidant stress Oxidative stress Peroxiredoxin VI |
| Zdroj: | Redox Biology Redox Biology, Vol 14, Iss, Pp 41-46 (2018) |
| Popis: | Although lipid peroxidation associated with oxidative stress can result in cellular death, sub-lethal lipid peroxidation can gradually resolve with return to the pre-exposure state. We have shown that resolution of lipid peroxidation is greatly delayed in lungs or cells that are null for peroxiredoxin 6 (Prdx6) and that both the phospholipase A2 and the GSH peroxidase activities of Prdx6 are required for a maximal rate of recovery. Like other peroxiredoxins, Prdx6 can reduce H2O2 and short chain hydroperoxides, but in addition can directly reduce phospholipid hydroperoxides. This study evaluated the relative role of these two different peroxidase activities of Prdx6 in the repair of peroxidized cell membranes. The His26 residue in Prdx6 is an important component of the binding site for phospholipids. Thus, we evaluated the lungs from H26A-Prdx6 expressing mice and generated H26A-Prdx6 expressing pulmonary microvascular endothelial cells (PMVEC) by lentiviral infection of Prdx6 null cells to compare with wild type in the repair of lipid peroxidation. Isolated lungs and PMVEC were exposed to tert-butyl hydroperoxide and mice were exposed to hyperoxia (> 95% O2). Assays for lipid peroxidation in wild type control and mutant lungs and cells showed ~4-fold increase at end-exposure. Control lungs and cells showed gradual resolution during a post-exposure recovery period. However, there was no recovery from lipid peroxidation by H26A-Prdx6 lungs or PMVEC. These studies confirm an important role for Prdx6 in recovery from membrane lipid peroxidation and indicate that reduction of H2O2 or short chain hydroperoxides does not play a role in the recovery process. Graphical abstract Conclusion: all 3 enzymatic activities of Prdx6 contribute to the reversal of cell membrane phospholipid peroxidation.fx1 Highlights • Repair of peroxidized lipids did not occur with H26A-Prdx6 Delete semicolons;mutation. • Repair reflects the phospholipid hydroperoxidase and PLA2 activities of Prdx6;Move to next with "bullet mark" "P"eroxidase activity with small hydroperoxides and H2O2 does not play a role in repair. |
| Databáze: | OpenAIRE |
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