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
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.