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

World Journal of Gastroenterology : WJG
Uwe GrutznerAngelika M Vollmar

Abstract

To investigate the in vivo effect of atrial natriuretic peptide (ANP) and its signaling pathway during orthotopic rat liver transplantation. Rats were infused with NaCl, ANP (5 microg/kg), wortmannin (WM, 16 microg/kg), or a combination of both for 20 min. Livers were stored in UW solution (4 degrees 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. 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. 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.

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Citations

Jul 7, 2007·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Carolyn J Mullonkal, Luis H Toledo-Pereyra
Dec 9, 2010·Journal of Pineal Research·Chi Hyun KimYeong-Min Yoo
Jul 28, 2016·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·Stephen M CovingtonLuis H Toledo-Pereyra
Sep 18, 2009·Journal of Natural Products·Andreas HartkornStefan Zahler

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