title: Activation of endoplasmic reticulum stress response following trauma-hemorrhage.
abstract: 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.
authors.affiliation: Center for Surgical Research, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Bixi
authors.initials: B
authors.lastname: Jian
authors.forename: Chi-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Mashkoor
authors.initials: M
authors.lastname: Choudhry
authors.forename: Kirby
authors.initials: K
authors.lastname: Bland
authors.forename: Irshad
authors.initials: I
authors.lastname: Chaudry
authors.forename: Raghavan
authors.initials: R
authors.lastname: Raju
mesh_terms: 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
chemical_list: 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
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