title: Increased expression of acetylcholinesterase T and R transcripts during hematopoietic differentiation is accompanied by parallel elevations in the levels of their respective molecular forms.
abstract: Differentiation of hematopoietic cells is known to be accompanied by profound changes in acetylcholinesterase (AChE) enzyme activity, yet the basic mechanisms underlying this developmental regulation remain unknown. We initiated a series of experiments to examine the molecular mechanisms involved in regulating AChE expression during hematopoiesis. Differentiation of murine erythroleukemia (MEL) cells using dimethyl sulfoxide resulted in a 5- and 10-fold increase in intracellular and secreted AChE enzyme activity, respectively. Interestingly, these increases resulted from a preferential induction of the globular molecular form G1 and a slight increase in G4 instead of an increase in the levels of the G2 membrane-bound form, a molecular form expressed in mature erythrocytes. Concomitantly, expression of the two predominant AChE transcripts (R and T, for read-through and tail, respectively) in MEL cells was induced to a similar extent with differentiation. Nuclear run-on assays performed with nuclei isolated from induced versus uninduced MEL cells revealed that in contrast to the large increases seen in the transcription of the beta-globin gene, the transcriptional activity of the AChE gene remained largely unaffected after differentiation. Determination of the half-lives of the R and T transcripts demonstrated that they both exhibited an increase in stability in induced MEL cells. Taken together, results from these studies indicate that post-transcriptional regulatory mechanisms account for the increased expression of AChE in differentiated hematopoietic cells.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors.forename: R Y
authors.initials: RY
authors.lastname: Chan
authors.forename: F A
authors.initials: FA
authors.lastname: Adatia
authors.forename: A M
authors.initials: AM
authors.lastname: Krupa
authors.forename: B J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D000110:Acetylcholinesterase / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006410:Hematopoiesis; D007527:Isoenzymes / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008970:Molecular Weight; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D003609:Dactinomycin; D000110:Acetylcholinesterase; D004121:Dimethyl Sulfoxide