Activation of endoplasmic reticulum stress response following trauma-hemorrhage

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1782

Article

Jian, Bixi¹  Hsieh, Chi-Hsun¹  Chen, Jianguo¹  Choudhry, Mashkoor^1,2  Bland, Kirby¹  Chaudry, Irshad^1,2  Raju, Raghavan^1,2 

[1] Univ Alabama, Dept Surg, Surg Res Ctr, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA

关键词: ER stress;    Trauma;    Hemorrhage;    Shock;    Hypoxia;    Apoptosis;   

DOI  :  10.1016/j.bbadis.2008.08.007

来源: Elsevier

【 摘 要 】

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, IRE1 alpha, 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. (c) 2008 Elsevier B.V. All rights reserved

【 授权许可】

Free