Gene Transduction of an Active Mutant of Akt Exerts Cytoprotection and Reduces Graft Injury After Liver Transplantation
作者： M. Morales-Ruiz , C. Fondevila , J. Muñoz-Luque , S. Tugues , G. Rodríguez-Laiz
DOI: 10.1111/J.1600-6143.2006.01720.X
关键词:
摘要: Akt is expected to be an effective target for the treatment of ischemia-reperfusion injury (I/R) due its anti-apoptotic properties and ability activate endothelial nitric oxide synthase (eNOS) enzyme. Therefore, this study was aimed determine efficacy active mutant (myr-Akt) decrease I/R in a model orthotopic liver transplantation pigs. In addition, we analyzed contribution Akt-mediated effects by using eNOS (S1179DeNOS) that mimics phosphorylation promoted sequence. Donors were treated with adenoviruses codifying myr-Akt, S1179DeNOS or β-galactosidase 24 h before harvesting. Then, grafts orthotopically transplanted into their corresponding recipients. Levels transaminases lactate dehydrogenase (LDH) increased all recipients after transplant. However, LDH levels significantly lower myr-Akt group compared vehicle. The percentage apoptotic cells amount activated-caspase 3 protein also markedly reduced myr-Akt-treated 4 days transplant vehicle groups. conclusion, gene therapy effectively exerts cytoprotection against hepatic regardless Akt-dependent activation.
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sci-hub.se 参考文章(47)
LUIS H. TOLEDO-PEREYRA, FRANCISCO J. RODRIGUEZ, DOLORES CEJALVO, Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Modulating effects of FK506 and cyclosporine. Transplantation. ,vol. 55, pp. 1265- 1271 ,(1993) , 10.1097/00007890-199306000-00011
N A Essani, H Jaeschke, A M Manning, G M McGuire, Endotoxin-induced activation of the nuclear transcription factor kappa B and expression of E-selectin messenger RNA in hepatocytes, Kupffer cells, and endothelial cells in vivo. Journal of Immunology. ,vol. 156, pp. 2956- 2963 ,(1996)
Stefanie Dimmeler, Ingrid Fleming, Beate Fisslthaler, Corinna Hermann, Rudi Busse, Andreas M. Zeiher, Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation Nature. ,vol. 399, pp. 601- 605 ,(1999) , 10.1038/21224
Osman Nidai Ozes, Lindsey D Mayo, Jason A Gustin, Susan R Pfeffer, Lawrence M Pfeffer, David B Donner, None, NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase Nature. ,vol. 401, pp. 82- 85 ,(1999) , 10.1038/43466
David Fulton, Jean-Philippe Gratton, Timothy J. McCabe, Jason Fontana, Yasushi Fujio, Kenneth Walsh, Thomas F. Franke, Andreas Papapetropoulos, William C. Sessa, Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature. ,vol. 399, pp. 597- 601 ,(1999) , 10.1038/21218
Ulrich Förstermann, Endothelial NO synthase as a source of NO and superoxide European Journal of Clinical Pharmacology. ,vol. 62, pp. 5- 12 ,(2006) , 10.1007/S00228-005-0006-X
Yasushi Fujio, Kenneth Walsh, Akt Mediates Cytoprotection of Endothelial Cells by Vascular Endothelial Growth Factor in an Anchorage-dependent Manner Journal of Biological Chemistry. ,vol. 274, pp. 16349- 16354 ,(1999) , 10.1074/JBC.274.23.16349
Naeem A. Essani, Michael A. Fisher, Hartmut Jaeschke, Inhibition Of Nf-kb Activation By Dimethyl Sulfoxide Correlates With Suppression Of Tnf-α Formation, Reduced Icam-1 Gene Transcription, And Protection Against Endotoxin-induced Liver Injury Shock. ,vol. 7, pp. 90- 96 ,(1997) , 10.1097/00024382-199702000-00003
Ramona S Scotland, Manuel Morales-Ruiz, Yan Chen, Jun Yu, Radu Daniel Rudic, David Fulton, Jean-Philippe Gratton, William C Sessa, None, Functional Reconstitution of Endothelial Nitric Oxide Synthase Reveals the Importance of Serine 1179 in Endothelium-Dependent Vasomotion Circulation Research. ,vol. 90, pp. 904- 910 ,(2002) , 10.1161/01.RES.0000016506.04193.96
Friedrich L??ngle, Rudolf Steininger, Elke Waldmann, Thomas Gr??nberger, Heike Benditte, Martina Mittlb??ck, Thomas Soliman, Martin Schindl, Ursula Windberger, Ferdinand M??hlbacher, Erich Roth, Improvement of cardiac output and liver blood flow and reduction of pulmonary vascular resistance by intravenous infusion of L-arginine during the early reperfusion period in pig liver transplantation Transplantation. ,vol. 63, pp. 1225- 1233 ,(1997) , 10.1097/00007890-199705150-00007