TY - JOUR
T1 - Activation of endoplasmic reticulum stress response following trauma-hemorrhage
AU - Jian, Bixi
AU - Hsieh, Chi Hsun
AU - Chen, Jianguo
AU - Choudhry, Mashkoor
AU - Bland, Kirby
AU - Chaudry, Irshad
AU - Raju, Raghavan
N1 - Funding Information:
The authors acknowledge the help of Dr Wenhong Kan in her assistance in the ELISA assay. The study was supported by NIH grant R21AG031440.
PY - 2008/11
Y1 - 2008/11
N2 - 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, IRE1α, 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.
AB - 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, IRE1α, 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.
KW - Apoptosis
KW - ER stress
KW - Hemorrhage
KW - Hypoxia
KW - Shock
KW - Trauma
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U2 - 10.1016/j.bbadis.2008.08.007
DO - 10.1016/j.bbadis.2008.08.007
M3 - Article
C2 - 18801427
AN - SCOPUS:55049106952
SN - 0925-4439
VL - 1782
SP - 621
EP - 626
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 11
ER -