Activation of endoplasmic reticulum stress response following trauma-hemorrhage.
Hemorrhagic trauma leads to organ dysfunction, sepsis and death. There is abnormal production of proinflammatory cytokines by Kupffer cells, tissue hypoxia and liver injury following trauma-hemorrhage. The physiological conditions consequent to trauma-hemorrhage are consistent with factors necessary to initiate endoplasmic reticulum (ER) stress and unfolded protein response. However, the contribution of ER stress to apoptosis and liver injury after trauma-hemorrhage is not known. In the present study ER stress was investigated in mice that underwent trauma-hemorrhage or sham operation. Expressions of endoplasmic reticulum stress proteins Bip, ATF6, PERK, IRE1alpha, and PDI were significantly elevated in the liver after trauma-hemorrhage compared to the controls. The ER stress associated proapoptotic transcription factor CHOP protein expression was also significantly elevated in trauma-hemorrhage group. Consistent with this, enhanced DNA fragmentation was observed, confirming apoptosis, in the liver following trauma-hemorrhage. These results demonstrate the initiation of ER stress and its role in apoptosis and liver injury, subsequent to hemorrhagic trauma.
Jian
Bixi
B
Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hsieh
Chi-Hsun
CH
Chen
Jianguo
J
Choudhry
Mashkoor
M
Bland
Kirby
K
Chaudry
Irshad
I
Raju
Raghavan
R
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006470:Hemorrhage / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018832:Molecular Chaperones / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D013312:Stress, Physiological; D014947:Wounds and Injuries / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism
D051702:Activating Transcription Factor 6; D015415:Biomarkers; D000091342:Endoplasmic Reticulum Chaperone BiP; D004722:Endoribonucleases; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; C497112:Atf6 protein, mouse; C510185:Ern1 protein, mouse
Science. 2000 Jan 28;287(5453):664-6
10650002
Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H2982-7
17293487
Surgery. 2000 Aug;128(2):246-52
10922999
Shock. 2000 Sep;14(3):347-53
11028555
Nat Cell Biol. 2000 Nov;2(11):E207-9
11056553
Mol Cell. 2000 Dec;6(6):1355-64
11163209
J Clin Invest. 2002 Nov;110(10):1389-98
12438434
Am J Physiol Gastrointest Liver Physiol. 2003 Jan;284(1):G107-15
12388175
J Pharmacol Exp Ther. 2003 Jan;304(1):172-8
12490588
Am J Physiol Gastrointest Liver Physiol. 2003 Dec;285(6):G1293-9
14613921
Endocrinology. 2004 Nov;145(11):5168-76
15297437
Biochemistry. 1991 Jan 22;30(3):613-9
1988050
Cytokine. 1992 Jan;4(1):66-75
1319764
Shock. 1995 Jun;3(6):395-7
7656061
Genes Dev. 1998 Apr 1;12(7):982-95
9531536
Arch Surg. 1999 Apr;134(4):368-73; discussion 373-4
10199308
J Biochem. 2004 Sep;136(3):261-5
15598880
Mutat Res. 2005 Jan 6;569(1-2):29-63
15603751
Annu Rev Biochem. 2005;74:739-89
15952902
Cancer Res. 2005 Jul 1;65(13):5785-91
15994954
Crit Rev Biochem Mol Biol. 2005 Sep-Oct;40(5):269-83
16257827
Cell. 2006 Feb 10;124(3):587-99
16469704
Curr Mol Med. 2006 Feb;6(1):45-54
16472112
Crit Care Med. 2006 Apr;34(4):1273-5
16550090
Shock. 2006 Mar;25(3):214-26
16552352
Brain Res. 2006 May 4;1087(1):60-6
16684512
Am J Pathol. 2006 Sep;169(3):784-94
16936255
EMBO Rep. 2006 Sep;7(9):880-5
16953201
J Mol Cell Cardiol. 2006 Sep;41(3):511-21
16859701
J Immunol. 2006 Oct 1;177(7):4514-20
16982888
J Surg Res. 2007 Jan;137(1):46-52
17101152
Mol Immunol. 2007 Mar;44(9):2165-72
17182102
Mol Immunol. 2007 Apr;44(10):2625-30
17239439
Am J Pathol. 2007 Apr;170(4):1210-8
17392161
FEBS Lett. 2007 Jul 31;581(19):3641-51
17481612
J Leukoc Biol. 2007 Oct;82(4):1019-26
17656650
Toxicology. 2007 Nov 30;241(3):146-56
17928124
Antioxid Redox Signal. 2007 Dec;9(12):2373-87
17883326
Antioxid Redox Signal. 2007 Dec;9(12):2241-4
17979526
Science. 2007 Nov 9;318(5852):944-9
17991856
Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19989-94
18056632
Shock. 2007 Nov;28(5):576-81
18084824
Am J Physiol Gastrointest Liver Physiol. 2008 Feb;294(2):G498-505
18174271
J Leukoc Biol. 2008 Mar;83(3):553-7
17984288
Mol Med. 2008 Mar-Apr;14(3-4):213-21
18235843
Cell Metab. 2008 Jun;7(6):520-32
18522833
J Appl Physiol (1985). 2008 Aug;105(2):595-602
18535130
Genes Dev. 1998 Jun 15;12(12):1812-24
9637683
J Hepatol. 2007 Jun;46(6):1047-54
17336418
Cell. 2000 May 26;101(5):451-4
10850487