Identification of hybrid cholinesterase forms consisting of acetyl- and butyrylcholinesterase subunits in human glioma

Brain and non-brain tumors contain acetylcholinesterase (AChE) and butyrylc holinesterase (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 Bu ChE 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), I LIS (ChE-II), and 10.5S (ChE-III). ChE-I was unretained. ChE-II w as weakly retained and ChE-III was adsorbed to edrophonium-agarose. confirm ing the AChE nature of the latter. ChE-I and ChE-II tetramers contained BuC hE subunits as shown by their binding with an antiserum against BuChE. The ChE activity of the immunocomplexes made with ChE-II and anti-BuChE antibod ies decreased with the AChE inhibitor BW284c51, revealing that ChE-II was m ade 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 Ch E-III, but not to ChE-I. demonstrated the hybrid composition of ChE-II. A s ubstantial fraction of the AChE tetramers and dimers of astrocytomas and ol igodendrogliomas bound both to anti-AChE and anti-BuChE antibodies, which r evealed a mixed composition of AChE and BuChE subunits in them. The AChE co mponents of brain, meningiomas and neurinomas were only recognized by AE1 In conclusion. our results demonstrate that aberrant ChE oligomers consisti ng of AChE and BuChE subunits are generated in astrocytomatous cyst and gli omas but not in brain, meningiomas or neurinomas. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.