title: Transglutaminase 2 protects against ischemic stroke.
abstract: Transglutaminase 2 (TG2) is a multifunctional protein that modulates cell survival and death pathways. It is upregulated in numerous ischemic models, and protects primary neurons from oxygen and glucose deprivation. TG2 binds to the hypoxia inducible factor (HIF) 1beta and decreases the upregulation of hypoxic-induced proapoptotic genes. To investigate the role of TG2 in ischemic stroke in vivo, we used the murine, permanent middle cerebral artery (MCA) ligation model. TG2 mRNA levels are increased after MCA ligations, and transgenic mice that express human TG2 in neurons had significantly smaller infarct volumes than wild type littermates. Further, TG2 translocates into the nucleus within 2h post ligation. Nuclear-localized TG2 is also apparent in human stroke cases. TG2 suppressed the upregulation of the HIF-induced, proapoptotic gene, Noxa. The findings of this study indicate that TG2 plays a role in attenuating ischemic-induced cell death possibly by modulating hypoxic-induced transcriptional processes.
authors.affiliation: Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Filiano
authors.forename: J
authors.initials: J
authors.lastname: Tucholski
authors.forename: P J
authors.initials: PJ
authors.lastname: Dolan
authors.forename: G
authors.initials: G
authors.lastname: Colak
authors.forename: G V W
authors.initials: GV
authors.lastname: Johnson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
references.citation: Oncogene. 2010 Jan 21;29(3):356-67
references.pmid: 19838207
references.citation: Nature. 1999 May 20;399(6733):271-5
references.pmid: 10353251
references.citation: Mol Cell Neurosci. 2007 Jan;34(1):40-7
references.pmid: 17101276
references.citation: J Cereb Blood Flow Metab. 1981;1(1):53-60
references.pmid: 7328138
references.citation: Neurobiol Dis. 2006 Jan;21(1):18-28
references.pmid: 16040250
references.citation: Exp Cell Res. 2006 Oct 1;312(16):2973-82
references.pmid: 16914140
references.citation: Neuroscience. 1995 Apr;65(4):1063-76
references.pmid: 7617162
references.citation: J Neurosci. 2007 Jun 6;27(23):6320-32
references.pmid: 17554006
references.citation: J Neurosci. 2005 Apr 20;25(16):4099-107
references.pmid: 15843612
references.citation: Brain Res. 1992 Apr 3;576(2):203-7
references.pmid: 1381261
references.citation: Neurobiol Dis. 2009 Mar;33(3):509-17
references.pmid: 19166937
references.citation: FASEB J. 2008 Aug;22(8):2662-75
references.pmid: 18375543
references.citation: Neuroreport. 1998 May 11;9(7):1317-9
references.pmid: 9631421
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 26;103(52):19683-8
references.pmid: 17179049
references.citation: Mol Cell Neurosci. 2004 Mar;25(3):493-503
references.pmid: 15033177
references.citation: J Neurochem. 2006 Apr;97(2):582-94
references.pmid: 16539654
references.citation: J Biol Chem. 2004 Jun 4;279(23):23863-8
references.pmid: 15069073
references.citation: FEBS Lett. 1999 Mar 5;446(1):35-9
references.pmid: 10100610
references.citation: PLoS One. 2009 Jul 01;4(7):e6123
references.pmid: 19568436
references.citation: EMBO J. 2005 Nov 16;24(22):3846-58
references.pmid: 16237459
references.citation: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4
references.pmid: 7539918
references.citation: PLoS Biol. 2007 Dec;5(12):e327
references.pmid: 18092889
references.citation: J Biol Chem. 1998 May 15;273(20):11991-4
references.pmid: 9575137
references.citation: Surg Neurol. 2007 Sep;68(3):297-303; discussion 303
references.pmid: 17368520
references.citation: Int J Dev Neurosci. 1993 Jun;11(3):325-37
references.pmid: 8102831
references.citation: J Biol Chem. 2002 Jun 7;277(23):20127-30
references.pmid: 11956182
references.citation: Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2743-7
references.pmid: 11867708
references.citation: Nat Rev Neurosci. 2004 Jun;5(6):437-48
references.pmid: 15152194
references.citation: J Neurosci. 1999 Aug 15;19(16):6818-24
references.pmid: 10436039
references.citation: J Biol Chem. 2004 Mar 5;279(10):8715-22
references.pmid: 14670969
references.citation: Exp Neurol. 2006 Dec;202(2):357-72
references.pmid: 16996500
references.citation: Brain Res. 2003 Jul 18;978(1-2):24-30
references.pmid: 12834894
references.citation: Cell Death Differ. 2006 Oct;13(10):1827-9
references.pmid: 16528383
references.citation: J Biol Chem. 1999 Oct 22;274(43):30715-21
references.pmid: 10521460
references.citation: Curr Mol Med. 2004 Mar;4(2):137-47
references.pmid: 15032710
references.citation: Neurosci Lett. 2004 Jun 10;363(2):173-7
references.pmid: 15172109
references.citation: Trends Biochem Sci. 2002 Oct;27(10):534-9
references.pmid: 12368090
references.citation: J Biol Chem. 2003 Jul 18;278(29):26838-43
references.pmid: 12743114
references.citation: J Cereb Blood Flow Metab. 2000 Jul;20(7):1011-32
references.pmid: 10908035
references.citation: Neurobiol Dis. 2008 Sep;31(3):433-41
references.pmid: 18602008
references.citation: Mol Biol Cell. 2007 Nov;18(11):4528-42
references.pmid: 17804822
references.citation: Cell Cycle. 2006 Jan;5(2):142-6
references.pmid: 16357535
references.citation: J Neurosci. 2008 Feb 20;28(8):1988-93
references.pmid: 18287515
references.citation: Biochem J. 2003 Aug 1;373(Pt 3):793-803
references.pmid: 12737632
references.citation: Brain Res. 2008 Sep 16;1230:281-9
references.pmid: 18657523
references.citation: Mol Cell Biol. 2004 May;24(9):3918-27
references.pmid: 15082785
references.citation: Cell Death Differ. 2001 Apr;8(4):367-76
references.pmid: 11550088
references.citation: J Am Soc Nephrol. 2005 Apr;16(4):986-96
references.pmid: 15743999
references.citation: J Biol Chem. 2010 Mar 5;285(10):6904-12
references.pmid: 20051518
references.citation: J Exp Med. 2004 Jan 5;199(1):113-24
references.pmid: 14699081
references.citation: Stroke. 2009 Feb;40(2):610-7
references.pmid: 19023096
references.citation: J Neurochem. 1999 Nov;73(5):2018-27
references.pmid: 10537061
references.citation: Biochemistry. 1995 Dec 5;34(48):15863-71
references.pmid: 7495818
references.citation: FASEB J. 2004 Sep;18(12):1462-4
references.pmid: 15240563
references.citation: PLoS One. 2008 Mar 26;3(3):e1861
references.pmid: 18365016
references.citation: Angiogenesis. 2008;11(2):121-40
references.pmid: 18327686
references.citation: Brain Pathol. 2009 Oct;19(4):612-22
references.pmid: 18673368
references.citation: Cancer Res. 2006 Apr 1;66(7):3688-98
references.pmid: 16585195
references.citation: Nat Rev Mol Cell Biol. 2003 Feb;4(2):140-56
references.pmid: 12563291
references.citation: J Neurochem. 2002 Jun;81(5):1061-72
references.pmid: 12065619
references.citation: Biochem Biophys Res Commun. 2008 Nov 28;376(4):743-7
references.pmid: 18809380
references.citation: J Biol Chem. 2005 Feb 4;280(5):3996-4003
references.pmid: 15557337
references.citation: J Neurochem. 2004 Jun;89(5):1301-7
references.pmid: 15147523