title: Critical role of peroxiredoxin 6 in the repair of peroxidized cell membranes following oxidative stress.
abstract: Phospholipids are a major structural component of all cell membranes; their peroxidation represents a severe threat to cellular integrity and their repair is important to prevent cell death. Peroxiredoxin 6 (Prdx6), a protein with both GSH peroxidase and phospholipase A(2) (PLA(2)) activity, plays a critical role in antioxidant defense of the lung and other organs. We investigated the role of Prdx6 in the repair of peroxidized cell membranes in pulmonary microvascular endothelial cells (PMVEC) and isolated mouse lungs treated with tert-butyl hydroperoxide and lungs from mice exposed to hyperoxia (100% O(2)). Lipid peroxidation was evaluated by measurement of thiobarbituric acid reactive substances, oxidation of diphenyl-1-pyrenylphosphine, or ferrous xylenol orange assay. The exposure dose was varied to give a similar degree of lipid peroxidation at the end of exposure in the different models. Values for lipid peroxidation returned to control levels within 2 h after oxidant removal in wild-type PMVEC and perfused lungs but were unchanged in Pxdx6 null preparations. An intermediate degree of repair was observed with PMVEC and lungs that expressed only C47S or D140A mutant Prdx6; the former mutant does not have peroxidase activity, while the latter loses its PLA(2) activity. Prdx6 null mice showed markedly delayed recovery from lipid peroxidation during 20 h observation following exposure to hyperoxia. Thus, Prdx6 plays a critical role in the repair of peroxidized phospholipids in cell membranes and the recovery of lung cells from peroxidative stress; the peroxidase and PLA(2) activity each contribute to the recovery process.
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Bavneet
authors.initials: B
authors.lastname: Benipal
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Suiping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Dodia
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Shampa
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Jian-Qin
authors.initials: JQ
authors.lastname: Tao
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Sorokina
authors.affiliation: Penn Gene Targeting Core and Laboratory of the Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Tobias
authors.initials: T
authors.lastname: Raabe
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
authors.affiliation: Institute for Environmental Medicine, Department of Physiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: abf@mail.med.upenn.edu.
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics*; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010544:Peroxidases / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2 / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000008:administration & dosage
chemical_list: D020122:tert-Butylhydroperoxide; D010544:Peroxidases; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse; D054467:Phospholipases A2
keywords: Diphenyl-1-pyrenylphosphine; Knock-in mice; Lipid peroxidation; Phospholipase A(2); Phospholipid hydroperoxide reductase; Pulmonary microvascular endothelial cells; Thiobarbituric acid reactive substances