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

نویسندگان

  • D Grisaru
  • V Deutsch
  • M Shapira
  • M Pick
  • M Sternfeld
  • N Melamed-Book
  • D Kaufer
  • N Galyam
  • M J Gait
  • D Owen
  • J B Lessing
  • A Eldor
  • H Soreq
چکیده

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. 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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Hydrolytic and nonenzymatic functions of acetylcholinesterase comodulate hemopoietic stress responses.

Glucocorticoid-initiated granulocytosis, excessive proliferation of granulocytes, persists after cortisol levels are lowered, suggesting the involvement of additional stress mediator(s). In this study, we report that the stress-induced acetylcholinesterase variant, AChE-R, and its cleavable, cell-penetrating C-terminal peptide, ARP, facilitate granulocytosis. In postdelivery patients, AChE-R-ex...

متن کامل

Antimicrobial Peptides Derived from Goat’s Milk Whey Proteins Obtained by Enzymatic Hydrolysis

In this study the bacterial growth inhibitory activity of peptide fragments produced from goat’s milk whey proteins by enzymatic hydrolysis using trypsin, ficin and a combination of both was investigated. Goat’s milk whey proteins were isolated and subjected to enzymatic hydrolysis and peptides were purified by ultrafiltration followed by reverse-phase high-performance liquid chromatography (RP...

متن کامل

Blood-cell-specific acetylcholinesterase splice variations under changing stimuli.

Developmental and trauma-induced mechanism(s) that modify inflammation and immune responses in blood cells were recently found to be regulated by acetylcholine. Here, we report corresponding blood cell-specific changes in acetylcholinesterase splice variants. Plasmon resonance and flow cytometry using acetylcholinesterase variant-specific antibody probes, revealed a progressive increase in myel...

متن کامل

Acetylcholinesterase enhances neurite growth and synapse development through alternative contributions of its hydrolytic capacity, core protein, and variable C termini.

Accumulated indirect evidence suggests nerve growth-promoting activities for acetylcholinesterase (AChE). To determine unequivocally whether such activities exist, whether they are related to the capacities of this enzyme to hydrolyze acetylcholine and enhance synapse development, and whether they are associated with alternative splicing variants of AChEmRNA, we used four recombinant human AChE...

متن کامل

Characterization of plant growth promoting rhizobacteria associated with chickpea (Cicer arietinum L.)

Plant growth promoting rhizobacteria (PGPR) are known to influence plant growth by various direct or indirect mechanisms. In search of efficient PGPR strains with multiple activities, a total of 150 bacterial isolates belonging to Bacillus, Pseudomonas, Azotobacter and Rhizobium were isolated from different rhizospheric soil of chick pea in the vicinity of Allahabad. These test isolates were bi...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Molecular medicine

دوره 7 2  شماره 

صفحات  -

تاریخ انتشار 2001