title: Dexmedetomidine attenuates oxidative stress induced lung alveolar epithelial cell apoptosis in vitro.
abstract: BACKGROUND
  Oxidative stress plays a pivotal role in the lung injuries of critical ill patients. This study investigates the protection conferred by α 2 adrenoceptor agonist dexmedetomidine (Dex) from lung alveolar epithelial cell injury induced by hydrogen peroxide (H2O2) and the underlying mechanisms.
  
  
  METHODS
  The lung alveolar epithelial cell line, A549, was cultured and then treated with 500 μM H2O2 with or without Dex (1 nM) or Dex in combination with atipamezole (10 nM), an antagonist of α 2 receptors. Their effect on mitochondrial membrane potential (Δψ m), reactive oxygen species (ROS), and the cell cycle was assessed by flow cytometry. Cleaved-caspases 3 and 9, BAX, Bcl-2, phospho-mTOR (p-mTOR), ERK1/2, and E-cadherin expression were also determined with immunocytochemistry.
  
  
  RESULTS
  Upregulation of cleaved-caspases 3 and 9 and BAX and downregulation of Bcl-2, p-mTOR, and E-cadherin were found following H2O2 treatment, and all of these were reversed by Dex. Dex also prevented the ROS generation, cytochrome C release, and cell cycle arrest induced by H2O2. The effects of Dex were partially reversed by atipamezole.
  
  
  CONCLUSIONS
  Our study demonstrated that Dex protected lung alveolar epithelial cells from apoptotic injury, cell cycle arrest, and loss of cell adhesion induced by H2O2 through enhancing the cell survival and proliferation.
authors.affiliation: Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China ; Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
authors.forename: Hailin
authors.identifier: 0000-0002-4736-5897
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
authors.forename: James J
authors.initials: JJ
authors.lastname: Sun
authors.affiliation: Department of Anaesthesiology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
authors.affiliation: Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
authors.forename: Daqing
authors.identifier: 0000-0002-0688-2097
authors.initials: D
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007093:Imidazoles / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D007093:Imidazoles; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; C050701:atipamezole; D020927:Dexmedetomidine; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053453:Caspase 9
references.citation: Anaesthesiol Intensive Ther. 2013 Oct-Dec;45(4):235-40
references.pmid: 24407902
references.citation: Methods Mol Biol. 2014;1170:279-93
references.pmid: 24906318
references.citation: Ann N Y Acad Sci. 2010 Aug;1203:53-9
references.pmid: 20716283
references.citation: Nanotoxicology. 2013 Sep;7(6):1095-110
references.pmid: 22769972
references.citation: Respir Physiol Neurobiol. 2014 Jan 1;190:118-23
references.pmid: 24148688
references.citation: Anaesthesia. 1999 Feb;54(2):146-65
references.pmid: 10215710
references.citation: Cell Mol Immunol. 2007 Dec;4(6):419-29
references.pmid: 18163953
references.citation: Indian J Anaesth. 2012 May;56(3):227-33
references.pmid: 22923819
references.citation: J Allergy Clin Immunol. 2008 Sep;122(3):456-68; quiz 469-70
references.pmid: 18774381
references.citation: Protein Cell. 2014 Oct;5(10):737-49
references.pmid: 25073422
references.citation: Am J Health Syst Pharm. 2013 May 1;70(9):767-77
references.pmid: 23592359
references.citation: Methodist Debakey Cardiovasc J. 2014 Apr-Jun;10(2):111-7
references.pmid: 25114763
references.citation: Metab Brain Dis. 2013 Jun;28(2):175-8
references.pmid: 23124921
references.citation: J Pediatr Pharmacol Ther. 2012 Jul;17(3):252-62
references.pmid: 23258968
references.citation: FEBS Lett. 2012 Nov 2;586(21):3767-70
references.pmid: 23022561
references.citation: Mol Pharmacol. 1997 May;51(5):711-20
references.pmid: 9145909
references.citation: Neurosci Lett. 2011 Oct 10;503(3):244-9
references.pmid: 21896310
references.citation: Cell Biochem Biophys. 2013;67(3):1547-50
references.pmid: 23733668
references.citation: Biochim Biophys Acta. 2003 Jan 20;1637(1):75-82
references.pmid: 12527410
references.citation: Methods Mol Biol. 2010;594:57-72
references.pmid: 20072909
references.citation: Cell Mol Life Sci. 2008 Nov;65(23):3756-88
references.pmid: 18726070
references.citation: EMBO J. 2005 Mar 23;24(6):1146-56
references.pmid: 15775979
references.citation: Clin Drug Investig. 2012 Aug 1;32(8):561-7
references.pmid: 22741747
references.citation: J Surg Res. 2011 May 15;167(2):e307-13
references.pmid: 19959187
references.citation: Am J Respir Cell Mol Biol. 2003 Oct;29(4):427-31
references.pmid: 14500253
references.citation: Inflammation. 2014 Oct;37(5):1763-70
references.pmid: 24803295
references.citation: Med Hypotheses. 2011 Sep;77(3):419-23
references.pmid: 21703771
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L291-305
references.pmid: 11435201