ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities
ARP, a peptide derived from the stress-associated acetylcholinesterase variant, has hematopoietic growth promoting activities
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DOI：
10.1007/bf03401943
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发表时间：
2001-02-01
影响因子：
5.7
通讯作者：
Soreq, H
中科院分区：
文献类型：
--
作者：
Grisaru, D;Deutsch, V;Soreq, H
工作背景：心理应激引起血细胞组成的快速和持久的变化，这意味着存在调节造血的应激诱导因子。在这里，我们报告了与应激相关的“通读”乙酰胆碱酯酶（AChE-R）变体及其26个氨基酸的C末端结构域（阿普）在造血应激反应中的参与。我们研究了应激、皮质醇、AChE反义寡核苷酸和合成阿普对正常和应激条件下小鼠外周血细胞组成和克隆祖细胞状态的影响，和人源的纯化的CD 34（+）细胞。我们采用原位杂交和免疫细胞化学染色，以监测基因表达，5-溴-2-脱氧尿苷（BrdU），原代液体培养，和克隆祖细胞测定相关AChE-R和阿普与造血祖细胞的增殖和分化。在人CD 34（+）造血祖细胞中，皮质醇升高AChE-R mRNA水平，促进造血扩增。在小鼠强迫游泳应激后，血清中出现与抗ARP抗血清交叉反应的小肽。离体，阿普是更有效的皮质醇和同样有效的干细胞因子在促进早期造血祖细胞的扩增和分化成髓系和megakaryocyte lineage.Conclusions：我们的研究结果属性AChE-R和阿普在造血稳态应激后的作用，并建议使用阿普在临床环境中，离体扩增的祖细胞是必需的。
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.