Butyrylcholinesterase activity and molecular components in thymus of healthy and merosin-deficient Lama2dy mice.
The laminin-alpha2 chain, referred to as merosin, forms part of the laminin-2 heterotrimer (alpha2beta1gamma1), which is principally expressed in the basement membrane of muscle. Nearly half of patients suffering from congenital muscular dystrophy (CMD) have abnormalities in the laminin-alpha2 chain (LAMA2) gene, and the merosin-deficient Lama2dy mouse shows CMD. The expression of merosin in thymus, the abnormalities in the gland of Lama2dy mice, and the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in thymus prompted us to study the possible effects of the deficiency of merosin on thymus BuChE. We found that, while AChE activity decreased by approximately 50% in merosin-deficient thymus, the deficiency had little effect on BuChE activity. About 65% of thymus BuChE activity was extracted with a saline buffer and 30% with 1% Triton X-100. Sedimentation analyses and phenyl-agarose chromatography showed that thymus contained amphiphilic BuChE monomers (G(1)(A),44%) and dimers (G(2)(A),33%), and hydrophilic tetramers (G(4)(H),23%). Binding assays with various plant lectins revealed differences between the oligoglycans linked to BuChE tetramers and lighter components. The deficiency of merosin had no effect on the biosynthesis of thymus BuChE as judged by the lack of major changes between control and Lama2dy mice thymuses in the distribution of BuChE molecules and the level of lectin binding. The detoxifying action of BuChE, its role as a backup to AChE, and the relevance of the cholinergic dialogue between T cells and stromal cells for T lymphocyte proliferation, maturation and survival support a physiological function for BuChE in thymus.
Sánchez del Campo
Luis F
LF
Departamento de Bioquímica y Biología Molecular-A, Universidad de Murcia, E-30071 Espinardo, Murcia, Spain.
Nieto-Cerón
Susana
S
Morote-García
Julio C
JC
Muñoz-Delgado
Encarnación
E
Vidal
Cecilio J
CJ
Campoy
Francisco J
FJ
D000818:Animals; D002091:Butyrylcholinesterase / Q000302:isolation & purification / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000502:physiology*; D051379:Mice; D013950:Thymus Gland / Q000201:enzymology*
D007797:Laminin; C102645:laminin alpha 2; D002091:Butyrylcholinesterase