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Titolo:
ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities
Autore:
Grisaru, D; Deutsch, V; Shapira, M; Pick, M; Sternfeld, M; Melamed-Book, N; Kaufer, D; Galyam, N; Gait, MJ; Owen, D; Lessing, JB; Eldor, A; Soreq, H;
Indirizzi:
Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91905 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91905 -91905 Jerusalem, Israel Tel Aviv Univ, Sackler Fac Med, Tel Aviv Sourasky Med Ctr, Dept Hematol, IL-69978 Tel Aviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 ematol, IL-69978 Tel Aviv, Israel MRC, Mol Biol Lab, Cambridge CB2 2QH, England MRC Cambridge England CB2 2QH , Mol Biol Lab, Cambridge CB2 2QH, England Tel Aviv Univ, Sackler Fac Med, Sourasky Med Ctr, Dept Obstet Gynecol, IL-69978 Tel Aviv, Israel Tel Aviv Univ Tel Aviv Israel IL-69978 ynecol, IL-69978 Tel Aviv, Israel
Titolo Testata:
MOLECULAR MEDICINE
fascicolo: 2, volume: 7, anno: 2001,
pagine: 93 - 105
SICI:
1076-1551(200102)7:2<93:AAPDFT>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEM-CELL FACTOR; COLONY-STIMULATING FACTOR; UMBILICAL-CORD BLOOD; BONE-MARROW HEMATOPOIESIS; MEGAKARYOCYTE PROGENITORS; MESSENGER-RNA; SELF-RENEWAL; RISK-FACTORS; EX-VIVO; GM-CSF;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
71
Recensione:
Indirizzi per estratti:
Indirizzo: Soreq, H Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91905 Jerusalem, Israel Hebrew Univ Jerusalem Jerusalem Israel IL-91905 rusalem, Israel
Citazione:
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

Abstract

Background: Psychological stress induces rapid and longlasting 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. Materials and 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 13:51:56