title: ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities.
abstract: BACKGROUND
  Psychological stress induces rapid and long-lasting changes in blood cell composition, implying the existence of stress-induced factors that modulate hematopoiesis. Here we report the involvement of the stress-associated "readthrough" acetylcholinesterase (AChE-R) variant, and its 26 amino acid C-terminal domain (ARP) in hematopoietic stress responses.
  
  
  METHODS
  We studied the effects of stress, cortisol, antisense oligonucleotides to AChE, and synthetic ARP on peripheral blood cell composition and clonogenic progenitor status in mice under normal and stress conditions, and on purified CD34 cells of human origin. We employed in situ hybridization and immunocytochemical staining to monitor gene expression, and 5-bromo-2-deoxyuridine (BrdU), primary liquid cultures, and clonogenic progenitor assays to correlate AChE-R and ARP with proliferation and differentiation of hematopoietic progenitors.
  
  
  RESULTS
  We identified two putative glucocorticoid response elements in the human ACHE gene encoding AChE. In human CD34+ hematopoietic progenitor cells, cortisol elevated AChE-R mRNA levels and promoted hematopoietic expansion. In mice, a small peptide crossreacting with anti-ARP antiserum appeared in serum following forced swim stress. Ex vivo, ARP was more effective than cortisol and equally as effective as stem cell factor in promoting expansion and differentiation of early hematopoietic progenitor cells into myeloid and megakaryocyte lineages.
  
  
  CONCLUSIONS
  Our findings attribute a role to AChE-R and ARP in hematopoietic homeostasis following stress, and suggest the use of ARP in clinical settings where ex vivo expansion of progenitor cells is required.
authors.affiliation: Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Grisaru
authors.forename: V
authors.initials: V
authors.lastname: Deutsch
authors.forename: M
authors.initials: M
authors.lastname: Shapira
authors.forename: M
authors.initials: M
authors.lastname: Pick
authors.forename: M
authors.initials: M
authors.lastname: Sternfeld
authors.forename: N
authors.initials: N
authors.lastname: Melamed-Book
authors.forename: D
authors.initials: D
authors.lastname: Kaufer
authors.forename: N
authors.initials: N
authors.lastname: Galyam
authors.forename: M J
authors.initials: MJ
authors.lastname: Gait
authors.forename: D
authors.initials: D
authors.lastname: Owen
authors.forename: J B
authors.initials: JB
authors.lastname: Lessing
authors.forename: A
authors.initials: A
authors.lastname: Eldor
authors.forename: H
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry*; D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000378:metabolism; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000378:metabolism / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D015854:Up-Regulation
chemical_list: D018952:Antigens, CD34; D016376:Oligonucleotides, Antisense; D010455:Peptides; D000110:Acetylcholinesterase; D001973:Bromodeoxyuridine; D006854:Hydrocortisone