title: Progression of apoptic signaling from mesenteric ischemia-reperfusion injury to lungs: correlation in the level of ER chaperones expression.
abstract: Multiple organ dysfunction syndrome (MODS) is characterized by the development of probably reversible, progressive dysfunction of vital systems in two or more organs, directly undamaged by surgery or other trauma. The organs which have the most common potential dysfunction are lungs, liver, kidneys, heart and gastrointestinal tract. The small intestine is the source of production of proinflammatory mediators leading and contributing to multiorgan failure. The endoplasmic reticulum (ER), after ischemia and post-ischemic reperfusion, is significantly involved in the activation of enterocyte apoptosis. The purpose of this study was to determine the stage of apoptosis in the lungs, initiated through inflammatory response from the small intestine. We analyzed changes in mRNA levels of pro-apoptotic genes Gadd153 (Chop) and anti-apoptotic genes Grp78 (Bip) in the small intestine wall and lung parenchyma. During experimental procedure the rats underwent 60 min of ischemia, caused by complete occlusion of the mesenteric arteria cranialis, with subsequent reperfusion and evaluation after 1 h, 24 h and 30 days (from R1, R24 to R30, respectively, each group n = 8). The gene expression levels were measured using RT-PCR followed by electrophoresis and visualization under UV. In the lungs we detected significantly lower level of expression Grp78 by 45 ± 6.9%. This suggests that ischemic attack and subsequent reperfusion did not promote ER stress in the lungs through induction of Gadd153 expression in the small intestine. There is still no effective approach to the treatment of affected ischemic intestine tissue, to stop the processes with could eventually lead to MODS. Therefore it is necessary to study changes in the damaged tissue at the molecular level and try to suggest possible therapeutic defined routes to the protection of tissue.
authors.affiliation: Department of Chemistry, Biochemistry, Medical Biochemistry and LABMED, Faculty of Medicine, Pavol Jozef Šafárik University, Kosice, Slovakia. phoenix19788@gmail.com
authors.forename: P
authors.initials: P
authors.lastname: Urban
authors.forename: M
authors.initials: M
authors.lastname: Bilecova-Rabajdova
authors.forename: M
authors.initials: M
authors.lastname: Marekova
authors.forename: J
authors.initials: J
authors.lastname: Vesela
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis; D002401:Cathepsin B / Q000096:biosynthesis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology; D008641:Mesenteric Vascular Occlusion / Q000473:pathology; D018832:Molecular Chaperones / Q000235:genetics; D009102:Multiple Organ Failure / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000096:biosynthesis* / Q000235:genetics; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D053148:Caspase 3; D002401:Cathepsin B; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP
references.citation: Am J Physiol Heart Circ Physiol. 2008 Apr;294(4):H1779-92
references.pmid: 18263716
references.citation: Am J Respir Cell Mol Biol. 2002 Jul;27(1):8-16
references.pmid: 12091240
references.citation: Shock. 1998 Sep;10(3):203-12
references.pmid: 9744649
references.citation: Exp Cell Res. 1999 Sep 15;251(2):401-13
references.pmid: 10471325
references.citation: Cell Mol Biol (Noisy-le-grand). 2005 Oct 03;51(5):513-20
references.pmid: 16309574
references.citation: Free Radic Biol Med. 2004 Nov 15;37(10):1670-9
references.pmid: 15477018
references.citation: J Surg Res. 1997 Jun;70(1):55-60
references.pmid: 9228928
references.citation: Chest. 1992 Jun;101(6):1644-55
references.pmid: 1303622
references.citation: Crit Care Med. 2001 Jul;29(7 Suppl):S99-106
references.pmid: 11445742
references.citation: Free Radic Biol Med. 2001 Jan 15;30(2):213-21
references.pmid: 11163539
references.citation: J Neurosci Res. 1999 Jul 1;57(1):48-61
references.pmid: 10397635
references.citation: J Biol Chem. 1997 Aug 29;272(35):21751-9
references.pmid: 9268304
references.citation: Crit Care Med. 2000 Feb;28(2):537-49
references.pmid: 10708197
references.citation: Acta Histochem. 2012 May;114(3):276-84
references.pmid: 21719076
references.citation: J Biol Chem. 1999 Oct 1;274(40):28645-51
references.pmid: 10497233
references.citation: Oncogene. 2008 Dec 4;27(53):6782-9
references.pmid: 18776923
references.citation: Exp Cell Res. 2001 Sep 10;269(1):64-72
references.pmid: 11525640
references.citation: Cancer Res. 2007 Jul 1;67(13):6270-7
references.pmid: 17616685
references.citation: Oncogene. 2001 Apr 19;20(17):2178-85
references.pmid: 11360202
references.citation: Shock. 2007 Aug;28(2):227-38
references.pmid: 17666944
references.citation: Hum Immunol. 2001 Aug;62(8):764-70
references.pmid: 11476899
references.citation: J Biol Chem. 1999 Apr 23;274(17):11549-56
references.pmid: 10206961
references.citation: Crit Care Med. 1999 Jul;27(7):1230-51
references.pmid: 10446814
references.citation: Prague Med Rep. 2010;111(4):249-56
references.pmid: 21189163
references.citation: Int J Cancer. 2002 Nov 1;102(1):7-14
references.pmid: 12353227
references.citation: Ann Surg. 2001 Jun;233(6):835-42
references.pmid: 11371742
references.citation: Oncogene. 2006 Jan 26;25(4):546-54
references.pmid: 16205645
references.citation: Cancer Biol Ther. 2006 Aug;5(8):1022-30
references.pmid: 16855386
references.citation: Exp Neurol. 1999 Feb;155(2):302-14
references.pmid: 10072306
references.citation: Shock. 2001 Jan;15(1):1-10
references.pmid: 11198350
references.citation: J Biol Chem. 1997 Jul 11;272(28):17588-93
references.pmid: 9211906
references.citation: FEBS Lett. 2002 Mar 13;514(2-3):122-8
references.pmid: 11943137
references.citation: Genes Dev. 1999 May 15;13(10):1211-33
references.pmid: 10346810
references.citation: Mol Cell Biol. 2001 Feb;21(4):1249-59
references.pmid: 11158311
references.citation: Acta Vet Hung. 2010 Jun;58(2):243-56
references.pmid: 20460223
references.citation: Scand J Infect Dis. 2003;35(9):593-600
references.pmid: 28443802
references.citation: Intensive Care Med. 1999 Jul;25(7):686-96
references.pmid: 10470572
references.citation: Ann Surg. 1992 Aug;216(2):117-34
references.pmid: 1503516