Changes in liver and plasma acetylcholinesterase in rats with cirrhosis induced by bile duct ligation.
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 (approximately 50%) compared with sham-operated (non-ligated, NL) controls; whereas liver BuChE appeared unaffected. A selective loss of tetrameric (G4) 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 G4 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 G4 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.
García-Ayllón
M Salud
MS
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Spain.
Silveyra
M Ximena
MX
Candela
Asunción
A
Compañ
Antonio
A
Clària
Joan
J
Jover
Rodrigo
R
Pérez-Mateo
Miguel
M
Felipo
Vicente
V
Martínez
Salvador
S
Galcerán
Joan
J
Sáez-Valero
Javier
J
D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D003135:Common Bile Duct; D006031:Glycosylation; D022781:Hepatocytes / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D012333:RNA, Messenger; D000110:Acetylcholinesterase