Published online Feb 21, 2006. doi: 10.3748/wjg.v12.i7.1049
Revised: July 2, 2005
Accepted: August 26, 2005
Published online: February 21, 2006
AIM: To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation.
METHODS: Rats were infused with NaCl, ANP (5 µg/kg), wortmannin (WM, 16 µg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4 °C) for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEL staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal microscopy.
RESULTS: ANP-pretreatment decreased caspase-3 activity and TUNEL-positive cells after cold ischemia, indicating antiapoptotic effects of ANP in vivo. The antiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepatocytes evoked by ANP.
CONCLUSION: ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad, an event triggering antiapoptotic signaling cascade in ischemic liver.