title: Adiponectin protects against hyperoxic lung injury and vascular leak.
abstract: Adiponectin (Ad), an adipokine exclusively secreted by the adipose tissue, has emerged as a paracrine metabolic regulator as well as a protectant against oxidative stress. Pharmacological approaches of protecting against clinical hyperoxic lung injury during oxygen therapy/treatment are limited. We have previously reported that Ad inhibits the NADPH oxidase-catalyzed formation of superoxide from molecular oxygen in human neutrophils. Based on this premise, we conducted studies to determine whether (i) exogenous Ad would protect against the hyperoxia-induced barrier dysfunction in the lung endothelial cells (ECs) in vitro, and (ii) endogenously synthesized Ad would protect against hyperoxic lung injury in wild-type (WT) and Ad-overexpressing transgenic (AdTg) mice in vivo. The results demonstrated that exogenous Ad protected against the hyperoxia-induced oxidative stress, loss of glutathione (GSH), cytoskeletal reorganization, barrier dysfunction, and leak in the lung ECs in vitro. Furthermore, the hyperoxia-induced lung injury, vascular leak, and lipid peroxidation were significantly attenuated in AdTg mice in vivo. Also, AdTg mice exhibited elevated levels of total thiols and GSH in the lungs as compared with WT mice. For the first time, our studies demonstrated that Ad protected against the hyperoxia-induced lung damage apparently through attenuation of oxidative stress and modulation of thiol-redox status.
authors.affiliation: Lipid Signaling, Lipidomics, and Vasculotoxicity Laboratory, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Dorothy M. Davis Heart & Lung Research Institute, Department of Internal Medicine, The Ohio State University College of Medicine, 473 W. 12th Avenue, Columbus, OH, 43210, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Sliman
authors.forename: Rishi B
authors.initials: RB
authors.lastname: Patel
authors.forename: Jason P
authors.initials: JP
authors.lastname: Cruff
authors.forename: Sainath R
authors.initials: SR
authors.lastname: Kotha
authors.forename: Christie A
authors.initials: CA
authors.lastname: Newland
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Schrader
authors.forename: Shariq I
authors.initials: SI
authors.lastname: Sherwani
authors.forename: Travis O
authors.initials: TO
authors.lastname: Gurney
authors.forename: Ulysses J
authors.initials: UJ
authors.lastname: Magalang
authors.forename: Narasimham L
authors.initials: NL
authors.lastname: Parinandi
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology*; D002417:Cattle; D015687:Cell Hypoxia / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D052242:Adiponectin; D017382:Reactive Oxygen Species; D005978:Glutathione