Akt activation protects rat liver from ischemia/reperfusion injury.

Apoptosis as well as necrosis may play an important role in hepatic ischemia/reperfusion (I/R) injury. Akt, a serine-threonine protein kinase, is known to promote cell survival. We investigated whether gene transfer of constitutively active or dominant negative Akt could affect hepatic I/R injury. Hepatic I/R injury was induced in rats by Pringle's maneuver for 20 min followed by reperfusion. Adenoviruses encoding a constitutively active form of Akt (myrAkt), a dominant negative form of Akt (dnAkt), or beta-galactosidase (LacZ) were injected through the tail vein 72 h before hepatic I/R. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining demonstrated a significant increase in the positive cells 240 min after reperfusion. Immunoblotting with phospho-Akt antibody showed phosphorylation of Akt from 90 to 180 min after reperfusion. The expression of myrAkt reduced the number of TUNEL-positive cells and hepatic necrosis around the central veins in the liver after reperfusion. This expression also significantly inhibited the increase in serum alanine aminotransferase (297 +/- 131 IU/L, P < 0.05) 120 min after I/R, compared with increases in uninfected (1761 +/- 671 IU/L), LacZ adenovirus (1528 +/- 671 IU/L)-, and dnAkt adenovirus (1342 +/- 485 IU/L)-infected rats. MyrAkt expression phosphorylated Bad and inhibited the release of cytochrome-c after reperfusion. No difference in nuclear translocation of nuclear factor (NF)-kappaB, p65 was seen among the three groups of rats, however. Adenoviral gene transfer of myrAkt could inhibit apoptotic cell death and subsequent hepatic I/R injury in the rat, through Bad, not NF-kappaB.

Harada N ，Hatano E ，Koizumi N ，Nitta T ，Yoshida M ，Yamamoto N ，Brenner DA ，Yamaoka Y ... -  《JOURNAL OF SURGICAL RESEARCH》

Adenovirus mediated gene transfer of antiapoptotic protein in hepatic ischemia-reperfusion injury: the paradoxical effect of Bcl-2 expression in the reperfused liver.

Oshiro T ，Shiraishi M ，Muto Y 《JOURNAL OF SURGICAL RESEARCH》

Attenuation of liver ischemia/reperfusion induced apoptosis by epigallocatechin-3-gallate via down-regulation of NF-kappaB and c-Jun expression.

Giakoustidis DE ，Giakoustidis AE ，Iliadis S ，Koliakou K ，Antoniadis N ，Kontos N ，Papanikolaou V ，Papageorgiou G ，Kaldrimidou E ，Takoudas D ... -  《-》

Activation of nuclear factor-kappaB during orthotopic liver transplantation in rats is protective and does not require Kupffer cells.

Bradham CA ，Schemmer P ，Stachlewitz RF ，Thurman RG ，Brenner DA ... -  《-》

Alpha-lipoic acid preconditioning reduces ischemia-reperfusion injury of the rat liver via the PI3-kinase/Akt pathway.

Müller C ，Dünschede F ，Koch E ，Vollmar AM ，Kiemer AK ... -  《AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY》