Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation

Abstract

Classical studies of cholinesterase activity during liver dysfunction have focused on butyrylcholinesterase (BuChE), whereas acetylcholinesterase (AChE) has not received much attention. In the current study, liver and plasma AChE levels were investigated in rats with cirrhosis induced after 3 weeks of bile duct ligation (BDL). BDL rats showed a pronounced decrease in liver AChE levels (ϳ50%) compared with sham-operated (non-ligated, NL) controls; whereas liver BuChE appeared unaffected. A selective loss of tetrameric (G 4 ) AChE was detected in BDL rats, an effect also observed in rats with carbon tetrachloride-induced cirrhosis. In accordance, SDS-PAGE analysis showed that the major 55-kd immunoreactive AChE band was decreased in BDL as compared with NL. A 65-kd band, attributed in part to inactive AChE, was increased as became the most abundant AChE subunit in BDL liver. The overall decrease in AChE activity in BDL liver was not accompanied by a reduction of AChE transcripts. The loss of G 4 was also reflected by changes observed in AChE glycosylation pattern attributable to different liver AChE forms being differentially glycosylated. BDL affects AChE levels in both hepatocytes and Kupffer cells; however, altered AChE expression was mainly reflected in an alteration in hepatocyte AChE pattern. Plasma from BDL rats had approximately 45% lower AChE activity than controls, displaying decreased G 4 levels and altered lectin-binding patterns. In conclusion, the liver is an important source of serum AChE; altered AChE levels may be a useful biomarker for liver cirrhosis. (HEPATOLOGY 2006; 43:444-453.)

Presenilin 1 Interacts with Acetylcholinesterase and Alters Its Enzymatic Activity and Glycosylation

“…Using nondenaturing polyacrylamide gels stained for AChE activity, the molecular masses of AChE subunits are in the range of 70 to 75 kDa. Analysis by SDS-PAGE and Western blotting by us and others, under fully reducing conditions and with several alternative anti-AChE antibodies, detected bands ranging from 75 to 60 kDa, as well as other species of 55 and 50 kDa, that may have originated by posttranslation modification (12,20,21,74). In a previous study, we confirmed the specificity of the major AChE bands, including the 55-kDa subunit, by AChE immunoprecipitation and probing blots with three alternative anti-human AChE antibodies (21).…”

“…This would correspond to the 55-kDa subunit that is contained within both AChE tetramers and monomers species (20,21); thus, it cannot be assigned to a particular AChE form. Accordingly, PS1 may coprecipitate either the G 4 or the G 1 ϩG 2 species or both of them.…”

“…First-strand cDNAs were obtained by reverse transcription using SuperScript III RT (Invitrogen Life Technologies) according to the manufacturer's instructions using 1 g of total RNA and oligo(dT) [12][13][14][15][16][17][18] . This assay consisted essentially of the methodology reported elsewhere (20). All cDNAs were normalized to GAPDH (glyceraldehyde-3-phosphate dehydrogenase).…”

Cholestasis progression effects on long-term memory in bile duct ligation rats

“…It has been shown that bile duct ligation after 3–4 weeks cause cirrhosis. [5242526] Mild cognitive impairment reported in patients with the liver cirrhosis. [27] Furthermore, in some patients with liver disease and signs of hyperamonia it has been showed that impaired attention, memory, cognitive function, and motor function.…”

“…[12] It has been shown that structural and functional impairment of the hepatobiliary systems[3] that cause a failure in bile secretion in hepatocytes or ductular cells or an impairment of bile flow and accumulation of bile salts in the body. [456]…”