title: Neuroglobin mitigates mitochondrial impairments induced by acute inhalation of combustion smoke in the mouse brain.
abstract: BACKGROUND
  Acute inhalation of combustion smoke adversely affects brain homeostasis and energy metabolism. We previously showed that overexpressed neuroglobin (Ngb), neuron specific globin protein, attenuates the formation of smoke inhalation-induced oxidative DNA damage, in vivo, in the mouse brain, while others reported protection by Ngb in diverse models of brain injury, mainly involving oxidative stress and hypoxic/ischemic insults.
  
  
  OBJECTIVE
  To determine to what extent elevated Ngb ameliorates post smoke-inhalation brain bioenergetics and homeostasis in Ngb overexpressing transgenic mouse.
  
  
  METHODS
  Smoke inhalation induced changes in bioenergetics were measured in the wild type and Ngb transgene mouse brain. Modulations of mitochondrial respiration were analyzed using the Seahorse XF24 flux analyzer and changes in cytoplasmic energy metabolism were assessed by measuring enzymatic activities and lactate in the course of post smoke recovery.
  
  
  RESULTS
  Cortical mitochondria from Ngb transgene, better maintained ATP synthesis-linked oxygen consumption and unlike wild type mitochondria did not increase futile oxygen consumption feeding the proton leak, reflecting lesser smoke-induced mitochondrial compromise. Measurements revealed lesser reduction of mitochondrial ATP content and lesser compensatory increases in cytosolic energy metabolism, involving pyruvate kinase and lactate dehydrogenase activities as well as cytosolic lactate levels. Additionally, induction of c-Fos, the early response gene and key neuronal stress sensor, was attenuated in Ngb transgene compared to wild type brain after smoke.
  
  
  CONCLUSIONS
  Considered together, these differences reflect lesser perturbations produced by acute inhalation of combustion smoke in the Ngb overexpressing mouse, suggesting that Ngb mitigates mitochondrial dysfunction and neurotoxicity and raises the threshold of smoke inhalation-induced brain injury.
authors.affiliation: Department of Surgery, University of Texas Medical Branch , Galveston, TX , USA.
authors.forename: Falih Murat
authors.initials: FM
authors.lastname: Gorgun
authors.forename: Ming
authors.initials: M
authors.lastname: Zhuo
authors.forename: Shilpee
authors.initials: S
authors.lastname: Singh
authors.forename: Ella W
authors.initials: EW
authors.lastname: Englander
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016762:Genes, fos; D005914:Globins / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000078787:Neuroglobin; D010101:Oxygen Consumption; D011770:Pyruvate Kinase / Q000378:metabolism; D015208:Smoke Inhalation Injury / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D000255:Adenosine Triphosphate; D005914:Globins; D007770:L-Lactate Dehydrogenase; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D011770:Pyruvate Kinase
references.citation: Free Radic Biol Med. 2007 Feb 1;42(3):385-93
references.pmid: 17210451
references.citation: Part Fibre Toxicol. 2013 Aug 01;10:34
references.pmid: 23902943
references.citation: Biochim Biophys Acta. 2012 Dec;1823(12):2261-73
references.pmid: 23036890
references.citation: Am J Physiol Cell Physiol. 2010 Aug;299(2):C464-76
references.pmid: 20445170
references.citation: PLoS One. 2011;6(7):e21746
references.pmid: 21799747
references.citation: Biochem Biophys Res Commun. 2013 Nov 22;441(3):624-9
references.pmid: 24177009
references.citation: Inhal Toxicol. 2008 Jun;20(8):761-6
references.pmid: 18569098
references.citation: Neuroscience. 2012 Aug 30;218:235-42
references.pmid: 22659017
references.citation: Neuro Endocrinol Lett. 2010;31(5):645-56
references.pmid: 21200377
references.citation: Free Radic Biol Med. 2011 Nov 1;51(9):1621-35
references.pmid: 21872656
references.citation: IUBMB Life. 2013 Mar;65(3):263-72
references.pmid: 23341346
references.citation: Cell Signal. 2005 Jul;17(7):799-808
references.pmid: 15763422
references.citation: J Biomed Sci. 2001 Jul-Aug;8(4):336-41
references.pmid: 11455196
references.citation: J Neurochem. 2003 Aug;86(3):591-604
references.pmid: 12859673
references.citation: Proteins. 2011 Jan;79(1):115-25
references.pmid: 20938977
references.citation: PLoS One. 2011;6(6):e20478
references.pmid: 21674044
references.citation: Brain Res. 2010 May 17;1331:58-73
references.pmid: 20331985
references.citation: FEBS Lett. 2006 Sep 4;580(20):4884-8
references.pmid: 16914148
references.citation: PLoS One. 2011;6(12):e28160
references.pmid: 22164238
references.citation: Neuroendocrinology. 2008;88(3):183-98
references.pmid: 18509243
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20087-92
references.pmid: 21041631
references.citation: Toxicol Lett. 2012 Sep 18;213(3):345-52
references.pmid: 22842584
references.citation: Toxicology. 1996 Dec 31;115(1-3):107-17
references.pmid: 9016744
references.citation: Anal Chem. 2009 Aug 15;81(16):6868-78
references.pmid: 19555051
references.citation: Free Radic Biol Med. 2011 Dec 15;51(12):2281-7
references.pmid: 22001746
references.citation: Toxicol Appl Pharmacol. 2009 Mar 1;235(2):208-15
references.pmid: 19133281
references.citation: Brain Res Brain Res Protoc. 2000 Feb;5(1):95-101
references.pmid: 10719270
references.citation: PLoS One. 2012;7(4):e34462
references.pmid: 22496809
references.citation: PLoS One. 2012;7(10):e47972
references.pmid: 23133533
references.citation: J Clin Invest. 2013 Apr;123(4):1405-12
references.pmid: 23543062
references.citation: J Exp Biol. 2009 May;212(Pt 10):1423-8
references.pmid: 19411534
references.citation: FEBS J. 2007 Mar;274(5):1312-7
references.pmid: 17286577
references.citation: Nature. 2000 Sep 28;407(6803):520-3
references.pmid: 11029004
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3497-500
references.pmid: 12621155
references.citation: Biochim Biophys Acta. 2003 Sep 23;1642(1-2):115-23
references.pmid: 12972300
references.citation: Biochim Biophys Acta. 2013 Sep;1834(9):1744-9
references.pmid: 23357651
references.citation: Neuropathol Appl Neurobiol. 2013 Aug;39(5):531-52
references.pmid: 23106634
references.citation: Rev Neurosci. 2013;24(3):323-35
references.pmid: 23612538
references.citation: Apoptosis. 2010 Apr;15(4):401-11
references.pmid: 20091232
references.citation: J Neurochem. 1986 Aug;47(2):496-505
references.pmid: 3734792
references.citation: Nat Protoc. 2008;3(6):1101-8
references.pmid: 18546601
references.citation: Neuroscience. 2009 May 19;160(3):698-709
references.pmid: 19285541
references.citation: Inhal Toxicol. 2010 Aug;22(9):770-7
references.pmid: 20429857
references.citation: Free Radic Biol Med. 2012 Nov 1;53(9):1782-90
references.pmid: 22841870
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8483-8
references.pmid: 15932948
references.citation: Biochem Biophys Res Commun. 2008 May 2;369(2):695-700
references.pmid: 18302932
references.citation: IUBMB Life. 2012 May;64(5):419-22
references.pmid: 22362590
references.citation: J Biol Chem. 2012 Aug 31;287(36):30128-38
references.pmid: 22787149
references.citation: Oxid Med Cell Longev. 2013;2013:756989
references.pmid: 23634236
references.citation: Biochem J. 2011 Apr 15;435(2):297-312
references.pmid: 21726199
references.citation: IUBMB Life. 2004 Nov-Dec;56(11-12):671-9
references.pmid: 15804831
references.citation: J Biol Chem. 2013 Oct 18;288(42):30485-30494
references.pmid: 24022484
references.citation: Free Radic Res. 2011 Aug;45(8):888-905
references.pmid: 21615270
references.citation: Toxicol Appl Pharmacol. 2005 Nov 1;208(3):255-65
references.pmid: 15893353
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17944-8
references.pmid: 17098866
references.citation: Free Radic Biol Med. 2011 Apr 1;50(7):866-73
references.pmid: 21215798
references.citation: J Neuroendocrinol. 2008 Jun;20(6):665-72
references.pmid: 18601687
references.citation: Nitric Oxide. 2013 Aug 1;32:21-8
references.pmid: 23587847
references.citation: Toxicology. 1996 Dec 31;115(1-3):7-23
references.pmid: 9016738
references.citation: Mech Ageing Dev. 2011 Oct;132(10):488-95
references.pmid: 21855562
references.citation: Nat Protoc. 2008;3(7):1228-39
references.pmid: 18600228
references.citation: J Biol Chem. 2004 May 28;279(22):22841-7
references.pmid: 15020597