PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptidein rat liver transplantation

• Published in: 世界胃肠病学杂志（英文版） 2006, Vol.12 (7), p.1049-1055
• Main Authors: Uwe Grutzner, Melanie Keller, Michael Bach, Alexandra K Kiemer, Herbert Meissner, Manfred Bilzer, Stefan Zahler, Alexander L Gerbes, Angelika M Vollmar
• Format: Article
• Language: English
• ISSN: 1007-9327

R5; 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 confocai microscopy.RESULTS: ANP-pretreatment decreased caspase-3activity 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.