Basic Research
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2006; 12(2): 228-233
Published online Jan 14, 2006. doi: 10.3748/wjg.v12.i2.228
Endothelial nitric oxide synthase regulation is altered in pancreas from cirrhotic rats
Jean-Louis Frossard, Rafael Quadri, Antoine Hadengue, Philippe Morel, Catherine M Pastor
Jean-Louis Frossard, Rafael Quadri, Antoine Hadengue.Division de Gastroenterologie, Hôpitaux Universitaires de Geneve
Philippe Morel, Departement de Chirurgie, Hôpitaux Universitaires de Geneve
Catherine M Pastor, Laboratoire de Physiopathologie Hepatique et Imagerie Moleculaire, Hôpitaux Universitaires de Geneve
Supported by the Fonds National Suisse de la Recherche Scientifique (No 3200-100868 to Dr. Catherine Pastor and No 3200-100764 to Dr. Jean-Louis Frossard)
Correspondence to: Catherine M. Pastor, MD, PhD, Laboratoire de Physiopathologie Hepatique et Imagerie Moleculaire, Hopitaux Universitaires de Genève, Bâtiment C, Room 6-795, Rue Micheli-du-Crest, 241211 Geneva 14, Switzerland. Catherine.Pastor@hcuge.ch
Telephone: + 41223729353 Fax:+ 41223729366
Received: May 18, 2005
Revised: June 8, 2005
Accepted: June 12, 2005
Published online: January 14, 2006
Abstract

AIM: To determine whether biliary cirrhosis could induce pancreatic dysfunction such as modifications in endothelial nitric oxide synthase(eNOS) expression and whether the regulation of eNOS could be altered by the regulatory proteins caveolin and heat shock protein 90 (Hsp90), as well as by the modifications of calmodulin binding to eNOS.

METHODS: Immunoprecipitations and Western blotting analysis were performed in pancreas isolated from sham and cirrhotic rats.

RESULTS: Pancreatic injury was minor in cirrhotic rats but eNOS expression importantly decreased with the length (and the severity) of the disease. Because co-immunoprecipitation of eNOS with both Hsp90 and caveolin similarly decreased in cirrhotic rats, eNOS activity was not modified by this mechanism. In contrast, cirrhosis decreased the calmodulin binding to eNOS with a concomitant decrease in eNOS activity.

CONCLUSION: In biliary cirrhosis, pancreatic injury is minor but the pancreatic nitric oxide (NO) production is significantly decreased by two mechanisms: a decreased expression of the enzyme and a decreased binding of calmodulin to eNOS.

Keywords: Pancreas; Biliary cirrhosis; Endothelial NO synthase; Caveolin; Heat shock protein 90