TY - JOUR
T1 - IGL-1 solution reduces endoplasmic reticulum stress and apoptosis in rat liver transplantation
AU - Mosbah, I. B.
AU - Zaouali, Ma
AU - Martel, C.
AU - Bjaoui, M.
AU - Abdennebi, H. B.
AU - Hotter, G.
AU - Brenner, C.
AU - Roselló-Catafau, J.
N1 - Funding Information:
Acknowledgements. We are grateful to Robin Rycroft at the language advisory service of the University of Barcelona for revising the English text. This work was supported by The Ministry of Health and Consumption (PI 081988), CIBER-ehd, Carlos III Institute, Madrid, Spain; Ministry of Foreign Affairs and International Cooperation (A/020255/08 and A/02987/09).
PY - 2012/3/1
Y1 - 2012/3/1
N2 - Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality.
AB - Injury due to cold ischemia reperfusion (I/R) is a major cause of primary graft non-function following liver transplantation. We postulated that I/R-induced cellular damage during liver transplantation might affect the secretory pathway, particularly at the endoplasmic reticulum (ER). We examined the involvement of ER stress in organ preservation, and compared cold storage in University of Wisconsin (UW) solution and in Institute Georges Lopez-1 (IGL-1) solution. In one group of rats, livers were preserved in UW solution for 8 h at 4 °C, and then orthotopic liver transplantation was performed according to Kamada's cuff technique. In another group, livers were preserved in IGL-1 solution. The effect of each preservation solution on the induction of ER stress, hepatic injury, mitochondrial damage and cell death was evaluated. As expected, we found increased ER stress after liver transplantation. IGL-1 solution significantly attenuated ER damage by reducing the activation of three pathways of unfolded protein response and their effector molecules caspase-12, C/EBP homologous protein-10, X-box-binding protein 1, tumor necrosis factor-associated factor 2 and eukaryotic translation initiation factor 2. This attenuation of ER stress was associated with a reduction in hepatic injury and cell death. Our results show that IGL-1 solution may be a useful means to circumvent excessive ER stress reactions associated with liver transplantation, and may optimize graft quality.
KW - Endoplasmic reticulum stress
KW - Ischemia injury
KW - Liver transplantation
KW - Oxidative stress
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=84859351533&partnerID=8YFLogxK
U2 - 10.1038/cddis.2012.12
DO - 10.1038/cddis.2012.12
M3 - Article
C2 - 22402603
AN - SCOPUS:84859351533
SN - 2041-4889
VL - 3
SP - e279
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 3
ER -