Document Detail


A single transient episode of hyperammonemia induces long-lasting alterations in protein kinase A.
MedLine Citation:
PMID:  17215436     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatic encephalopathy in patients with liver disease is associated with poor prognosis. This could be due to the induction by the transient episode of hepatic encephalopathy of long-lasting alterations making patients more susceptible. We show that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction. The content of the regulatory subunit of the protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from cirrhotic patients. This increase is reproduced in rats with portacaval anastomosis and in rats with hyperammonemia without liver failure, suggesting that hyperammonemia is responsible for increased PKA-RI in patients. We analyzed whether there is a correlation between ammonia levels and PKA-RI content in patients. All cirrhotic patients had increased content of PKA-RI. Some of them showed normal ammonia levels but had suffered previous hyperammonemia episodes. This suggested that a single transient episode of hyperammonemia could induce the long-lasting increase in PKA-RI. To assess this, we injected normal rats with ammonia and blood was taken at different times. Ammonia returned to basal levels at 2 h. However, PKA-RI was significantly increased in blood cells from rats injected with ammonia 3 wk after injection. In conclusion, it is shown that a single transient episode of hyperammonemia induces long-lasting alterations in signal transduction both in blood and brain. These alterations may contribute to the poor prognosis of patients suffering hepatic encephalopathy.
Authors:
Carmina Montoliu; Blanca Piedrafita; Miguel A Serra; Juan A del Olmo; José M Rodrigo; Vicente Felipo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  292     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-11     Completed Date:  2007-03-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G305-14     Citation Subset:  IM    
Affiliation:
Servicio de Hepatología, Hospital Clínico Universitario, Departamento de Medicina, Universidad de Valencia, Valencia, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Animals
Ascites / complications
Chronic Disease
Cyclic AMP-Dependent Protein Kinases / blood,  metabolism*
Disease Models, Animal
Erythrocyte Membrane / enzymology
Erythrocytes / enzymology
Female
Hepatitis / complications
Humans
Hyperammonemia / enzymology*,  etiology,  physiopathology*
Liver Cirrhosis / complications*
Liver Failure / blood,  complications
Liver Function Tests
Male
Middle Aged
Rats
Rats, Wistar
Reference Values
Chemical
Reg. No./Substance:
EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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