title: Novel Genes Critical for Hypoxic Preconditioning in Zebrafish Are Regulators of Insulin and Glucose Metabolism.
abstract: Severe hypoxia is a common cause of major brain, heart, and kidney injury in adults, children, and newborns. However, mild hypoxia can be protective against later, more severe hypoxia exposure via "hypoxic preconditioning," a phenomenon that is not yet fully understood. Accordingly, we have established and optimized an embryonic zebrafish model to study hypoxic preconditioning. Using a functional genomic approach, we used this zebrafish model to identify and validate five novel hypoxia-protective genes, including irs2, crtc3, and camk2g2, which have been previously implicated in metabolic regulation. These results extend our understanding of the mechanisms of hypoxic preconditioning and affirm the discovery potential of this novel vertebrate hypoxic stress model.
authors.affiliation: Division of Neonatology, University of California San Diego School of Medicine, La Jolla, California 92093.
authors.forename: Tania
authors.initials: T
authors.lastname: Manchenkov
authors.affiliation: Division of Neonatology, University of California San Diego School of Medicine, La Jolla, California 92093.
authors.forename: Martina P
authors.initials: MP
authors.lastname: Pasillas
authors.affiliation: Division of Respiratory Medicine, University of California San Diego School of Medicine, La Jolla, California 92093 Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California 92093 Rady Children's Hospital-San Diego, San Diego, California 92123.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Haddad
authors.affiliation: Division of Neonatology, University of California San Diego School of Medicine, La Jolla, California 92093 Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, California 92093 Rady Children's Hospital-San Diego, San Diego, California 92123 f2imam@ucsd.edu.
authors.forename: Farhad B
authors.identifier: http://orcid.org/0000-0003-2854-2568
authors.initials: FB
authors.lastname: Imam
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D016678:Genome; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics*; D007328:Insulin / Q000378:metabolism*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D013312:Stress, Physiological / Q000235:genetics; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000235:genetics* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D007328:Insulin; D029961:Zebrafish Proteins; D005947:Glucose
keywords: hormesis; hypoxia-ischemia; metabolic state; preconditioning; stress tolerance
references.citation: Dev Biol. 2006 Dec 15;300(2):554-69
references.pmid: 17055478
references.citation: Dev Dyn. 2008 Jul;237(7):1780-8
references.pmid: 18521954
references.citation: Cell Metab. 2013 Dec 3;18(6):803-15
references.pmid: 24268736
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14919-24
references.pmid: 12397179
references.citation: Nat Protoc. 2008;3(1):59-69
references.pmid: 18193022
references.citation: Mol Cell Biol. 2011 Feb;31(3):430-41
references.pmid: 21135130
references.citation: Gene. 2008 Aug 15;420(1):1-10
references.pmid: 18565696
references.citation: Proc Natl Acad Sci U S A. 2008 May 20;105(20):7321-6
references.pmid: 18477695
references.citation: Mol Cell Neurosci. 2001 Jul;18(1):119-30
references.pmid: 11461158
references.citation: Neuron. 2010 Jul 29;67(2):181-98
references.pmid: 20670828
references.citation: Bioessays. 2005 Nov;27(11):1147-57
references.pmid: 16237670
references.citation: Comp Biochem Physiol Part D Genomics Proteomics. 2007 Jun;2(2):177-86
references.pmid: 20483291
references.citation: Annu Rev Pathol. 2014;9:47-71
references.pmid: 23937437
references.citation: Cancer Res. 2012 Aug 15;72(16):4017-27
references.pmid: 22665266
references.citation: Science. 2002 Jun 28;296(5577):2388-91
references.pmid: 12065745
references.citation: Cell Metab. 2009 Mar;9(3):277-86
references.pmid: 19254572
references.citation: Dev Dyn. 1995 Jul;203(3):253-310
references.pmid: 8589427
references.citation: Nat Med. 2013 Oct;19(10):1325-30
references.pmid: 24037093
references.citation: Nat Med. 2013 Oct;19(10):1331-7
references.pmid: 24037094
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7331-5
references.pmid: 11404478
references.citation: Physiol Rev. 2012 Jul;92(3):967-1003
references.pmid: 22811423
references.citation: Development. 2010 Aug;137(16):2753-62
references.pmid: 20630945
references.citation: PLoS Genet. 2008 Oct;4(10):e1000221
references.pmid: 18927626
references.citation: J Exp Zool. 2001 Apr 1;289(4):266-72
references.pmid: 11241397
references.citation: J Intensive Care Med. 2009 Sep-Oct;24(5):293-316
references.pmid: 19703817
references.citation: Nature. 1998 Feb 26;391(6670):900-4
references.pmid: 9495343
references.citation: J Neurochem. 2012 Dec;123(6):954-62
references.pmid: 23043544
references.citation: Dev Dyn. 2007 Jan;236(1):295-305
references.pmid: 17103413
references.citation: Stat Appl Genet Mol Biol. 2004;3:Article3
references.pmid: 16646809
references.citation: Curr Opin Neurol. 2002 Apr;15(2):151-7
references.pmid: 11923628
references.citation: BMC Biol. 2009;7:7
references.pmid: 19196451
references.citation: PLoS One. 2009;4(12):e8150
references.pmid: 19997509
references.citation: Genes Dev. 1998 Jan 15;12(2):149-62
references.pmid: 9436976
references.citation: Hum Genet. 2003 Jul;113(1):34-43
references.pmid: 12687350
references.citation: G3 (Bethesda). 2012 Oct;2(10):1169-78
references.pmid: 23050227
references.citation: Blood. 2009 Jun 18;113(25):6449-60
references.pmid: 19304954
references.citation: J Cell Sci. 2005 Dec 1;118(Pt 23):5431-41
references.pmid: 16278294
references.citation: Dev Dyn. 2008 Jul;237(7):1789-98
references.pmid: 18521947
references.citation: Cell. 2010 Jul 9;142(1):133-43
references.pmid: 20603019
references.citation: Transl Stroke Res. 2013 Feb;4(1):51-5
references.pmid: 23565128
references.citation: Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1555-63
references.pmid: 11294781
references.citation: PLoS One. 2011;6(7):e22268
references.pmid: 21814572
references.citation: J Clin Invest. 2005 Mar;115(3):500-8
references.pmid: 15765131
references.citation: Dev Biol. 2005 Jul 1;283(1):97-112
references.pmid: 15890331
references.citation: Genome Res. 2012 Mar;22(3):577-91
references.pmid: 22110045
references.citation: Mol Cell. 2008 May 23;30(4):393-402
references.pmid: 18498744
references.citation: Dev Biol. 1999 May 15;209(2):254-67
references.pmid: 10328919
references.citation: Genesis. 2001 Jul;30(3):154-6
references.pmid: 11477696
references.citation: Nat Rev Neurosci. 2006 Jun;7(6):437-48
references.pmid: 16715053
references.citation: Circulation. 1986 Nov;74(5):1124-36
references.pmid: 3769170
references.citation: Proc Biol Sci. 2014 Jul 7;281(1786). pii: 20140637. doi: 10.1098/rspb.2014.0637
references.pmid: 24850928
references.citation: Nature. 2010 Dec 16;468(7326):933-9
references.pmid: 21164481
references.citation: Hum Mol Genet. 2000 Oct 12;9(17):2517-21
references.pmid: 11030756
references.citation: PLoS One. 2011;6(7):e22022
references.pmid: 21789205
references.citation: Zebrafish. 2009 Mar;6(1):69-77
references.pmid: 19374550
references.citation: Lancet. 2007 Sep 22;370(9592):1089-100
references.pmid: 17822755