Muscular dystrophy alters the processing of light acetylcholinesterase but not butyrylcholinesterase forms in liver of Lama2dy mice

Abstract

In order to know whether the histopathological changes of liver, which accompany muscular dystrophy, affect the synthesis of cholinesterases, the distribution and glycosylation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) forms in normal (NL) and dystrophic Lama2(dy) mouse liver (DL) were investigated. About half of liver AChE, and 25% of BuChE were released with a saline buffer (fraction S(1)), and the rest with a saline-Brij 96 buffer (S(2)). Abundant light (G(2)(A) and G(1)(A)) AChE (87%) and BuChE (93%) forms, and a few G(4)(H) and G(4)(A) ChE species were identified in liver. The dystrophic syndrome had no effect on solubilization or composition of ChE forms. Most of the light AChE and BuChE species (>95%) were bound by octyl-Sepharose, while most light AChE forms (80%), but not BuChE isoforms (15%), were retained in phenyl-agarose. About half of the AChE dimers lost their amphiphilic anchor with phosphatidylinositol-specific phospholipase C (PIPLC), and the fraction of PIPLC-resistant species increased in DL. AChE T and R transcripts were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) of liver RNA. ChE components of liver, erythrocyte, and plasma were distinguished by their amphiphilic properties and interaction with lectins. The dystrophic syndrome increased the liver content of the light AChE forms with Lens culinaris agglutinin (LCA) reactivity. The abundance of ChE tetramers in plasma and their small amount in liver suggest that after their assembly in liver they are rapidly secreted, while the light species remain associated to hepatic membranes.

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

“…Molecular forms of AChE were separated according to its sedimentation coefficients by centrifugation on 5% to 20% (w/v) sucrose gradients containing 0.5% (w/v) Triton X-100. 7,16 Ultracentrifugation was performed at 150,000g in an SW 41Ti Beckman rotor for 18 hours at 4°C. Approximately 40 fractions were collected from the bottom of each tube and assayed for cholinesterase activities.…”

“…28,29 We did not detect the H-transcript, which has been previously described to be scarce in adult rat liver. 7,27 Phosphatidylinositol-specific phospholipase Lectin Binding of Liver AChE. To further examine whether the glycosylation of AChE is altered in BDL rats, we determined the ability of AChE to bind to several immobilized lectins, proteins that avidly bind to specific sugar moieties of glycoproteins.…”

“…AChE may function in hepatocytes and other epithelial cells to inactivate blood-circulating acetylcholine. 7 However, AChE also may be involved in some intercellular and intracellular regulatory mechanisms. 4 In addition to enzymatic activity, a possible structural change of AChE may contribute to cellular alterations in liver cirrhosis, because roles for AChE other than its acetylcholine hydrolytic activity have been proposed, such as regulation of cell growth and cell adhesion.…”

“…Several authors have previously described the distribution of cholinesterases in the liver of rat, [3][4][5][6] mouse, 7 rabbit, 8,9 and chick. 10 However, no significant conclusion has been reached about the potential physiological role of AChE in the liver and whether liver is an important source for serum AChE.…”

La Estructura Y Función De Las Colinesterasas: Blanco De Los Plaguicidas

“…En mamíferos, la proteína BuChE se presenta en plasma, hígado y corazón. Se considera que el hígado es el órgano productor de la proteína BuChE que se detecta en el plasma (Gómez et al 1999(Gómez et al , 2000.…”