ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities

Citation
D. Grisaru et al., ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities, MOL MED, 7(2), 2001, pp. 93-105
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
MOLECULAR MEDICINE
ISSN journal
1076-1551 → ACNP
Volume
7
Issue
2
Year of publication
2001
Pages
93 - 105
Database
ISI
SICI code
1076-1551(200102)7:2<93:AAPDFT>2.0.ZU;2-X
Abstract
Background: Psychological stress induces rapid and longlasting changes in b lood cell composition, implying the existence of stress-induced factors tha t modulate hematopoiesis. Here we report the involvement of the stress-asso ciated "readthrough" acetylcholinesterase (AChE-R) variant, and its 26 amin o acid C-terminal domain (ARP) in hematopoietic stress responses. Materials and Methods: We studied the effects of stress, cortisol, antisens e oligonucleotides to AChE, and synthetic ARP on peripheral blood cell comp osition and clonogenic progenitor status in mice under normal and stress co nditions, and on purified CD34(+) cells of human origin. We employed in sit u 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 diffe rentiation of hematopoietic progenitors. Results: We identified two putative glucocorticoid response elements in the human ACHE gene encoding AChE. In human CD34(+) hematopoietic progenitor c ells, cortisol elevated AChE-R mRNA levels and promoted hematopoietic expan sion. In mice, a small peptide crossreacting with anti-ARP antiserum appear ed in serum following forced swim stress. Ex vivo, ARP was more effective t han cortisol and equally as effective as stem cell factor in promoting expa nsion and differentiation of early hematopoietic progenitor cells into myel oid and megakaryocyte lineages. Conclusions: Our findings attribute a role to AChE-R and ARP in hematopoiet ic homeostasis following stress, and suggest the use of ARP in clinical set tings where ex vivo expansion of progenitor cells is required.