Abstract
Background & AimsThere have been many studies on plasma butyrylcholinesterase in liver dysfunction. However, no data is available about acetylcholinesterase in human cirrhosis, although profound changes have been described in cirrhotic rat models.MethodsHuman serum and liver acetylcholinesterase and its molecular forms were determined enzymatically, after butyrylcholinesterase immunodepletion. The distinct species of acetylcholinesterase, with a distinct C-terminus, were determined by western blotting, and the level of liver transcripts by real-time PCR. Liver acetylcholinesterase was also evaluated by immunocytochemistry.ResultsIn patients with liver cirrhosis, the activity of plasma acetylcholinesterase (rich in light species), appeared to be apparently unaffected. However, the levels of the soluble readthrough (R) acetylcholinesterase form, an acetylcholinesterase species usually associated with stress and pathology, was increased compared to controls. Human liver acetylcholinesterase activity levels were also unchanged, but protein levels of the acetylcholinesterase-R and other acetylcholinesterase subunit species were increased in the cirrhotic liver. This increase in acetylcholinesterase protein expression in the cirrhotic liver was confirmed by PCR analysis. Immunohistological examination confirmed that acetylcholinesterase immunoreactivity is increased in parenchymal cells of the cirrhotic liver.ConclusionsWe demonstrate significant changes in acetylcholinesterase at the protein and mRNA levels in liver cirrhosis, with no difference in enzymatic activity. The altered expression of acetylcholinesterase protein may reflect changes in its pathophysiological role.
Highlights
Cholinesterases are a family of ubiquitous enzymes frequently studied in association with many pathological processes
Very few studies have addressed the levels of cholinesterase in human liver [8,9], it is widely accepted that plasma BChE originates in liver cells and represents the major cholinesterase in human serum, approximately 160 times higher than AChE [10]
Using the rat as an animal model with low serum BChE activity, we have reported that AChE is significantly altered during liver cirrhosis [13]
Summary
Cholinesterases are a family of ubiquitous enzymes frequently studied in association with many pathological processes. Acetylcholinesterase (EC 3.1.1.7; AChE), the enzyme responsible for the inactivation of cholinergic neurotransmission, has been associated to cognitive dysfunction in Alzheimer’s disease [1], and to disorders such as neuromuscular dysfunction and myasthenic syndromes, tumorigenesis among many others (for a review see [2,3,4]). AChE is present in serum and liver, its physiological significance other than inactivating acetylcholine has far not been elucidated. A second cholinesterase, butyrylcholinesterase (EC 3.1.1.8; BChE), whose physiological role is unknown, co-exists with AChE in many tissues, including those with no cholinergic function [2,5]. Previous studies on cholinesterase changes during liver dysfunction have focussed on serum BChE; whereas AChE has not received much attention. No data is available about acetylcholinesterase in human cirrhosis, profound changes have been described in cirrhotic rat models
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