Identification of hybrid cholinesterase forms consisting of acetyl- and butyrylcholinesterase subunits in human glioma.
Brain and non-brain tumors contain acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) transcripts and enzyme activity. AChE and BuChE occur in tissues as a set of molecular components, whose distribution in a cyst fluid from a human astrocytoma we investigated. The fluid displayed high BuChE and low AChE activities. Three types of cholinesterase (ChE) tetramers were identified in the fluid by means of sedimentation analyses and assays with specific inhibitors, and their sedimentation coefficients were 11.7S (ChE-I), 11.1S (ChE-II), and 10.5S (ChE-III). ChE-I was unretained, ChE-II was weakly retained and ChE-III was adsorbed to edrophonium-agarose, confirming the AChE nature of the latter. ChE-I and ChE-II tetramers contained BuChE subunits as shown by their binding with an antiserum against BuChE. The ChE activity of the immunocomplexes made with ChE-II and anti-BuChE antibodies decreased with the AChE inhibitor BW284c51, revealing that ChE-II was made of AChE and BuChE subunits, in contrast to ChE-I, which only contained BuChE subunits. The binding of an anti-AChE antibody (AE1) to ChE-II and ChE-III, but not to ChE-I, demonstrated the hybrid composition of ChE-II. A substantial fraction of the AChE tetramers and dimers of astrocytomas and oligodendrogliomas bound both to anti-AChE and anti-BuChE antibodies, which revealed a mixed composition of AChE and BuChE subunits in them. The AChE components of brain, meningiomas and neurinomas were only recognized by AE1. In conclusion, our results demonstrate that aberrant ChE oligomers consisting of AChE and BuChE subunits are generated in astrocytomatous cyst and gliomas but not in brain, meningiomas or neurinomas.
García-Ayllón
M S
MS
Departamento de Bioquímica y Biología Molecular-A, Edificio de Veterinaria, Universidad de Murcia, Apdo. 4021, E-30071 Espinardo, Murcia, Spain.
Sáez-Valero
J
J
Muñoz-Delgado
E
E
Vidal
C J
CJ
D000110:Acetylcholinesterase / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D000906:Antibodies; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000201:enzymology*; D002091:Butyrylcholinesterase / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D002846:Chromatography, Affinity; D005909:Glioblastoma / Q000201:enzymology; D005910:Glioma / Q000201:enzymology*; D006801:Humans; D008577:Meningeal Neoplasms / Q000378:metabolism; D008579:Meningioma / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000378:metabolism; D009837:Oligodendroglioma / Q000378:metabolism; D021122:Protein Subunits
D000906:Antibodies; D021122:Protein Subunits; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase