Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells

Extracellular nucleotides have multiple biological actions in processes such as proliferation, differentiation, chemotaxis, and cytokine secretion through P2X receptors on the cell surface. To determine the biological activity of adenosine triphosphate (ATP) and the expression of P2 nucleotide recep...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2007, Vol.30(4), pp.671-676
Main Authors: Yoon, Mi-Jung, Lee, Hyun-Joo, Lee, Yong-Soo, Kim, Jae-Hwan, Park, Jin-Ki, Chang, Won-Kyong, Shin, Ho-Chul, Kim, Dong-Ku
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - analogs & derivatives
Adenosine Triphosphate - pharmacology
Animals
antagonis
apoptosis
Apoptosis - drug effects
ATP
Bone Marrow Cells
Cell Proliferation - drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Femur - cytology
hematopoietic stem cell
Hematopoietic System - cytology
Hematopoietic System - drug effects
Hematopoietic System - metabolism
Mice
Mice, Inbred C57BL
P2X
proliferation
Purinergic P2 Receptor Antagonists
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X
Stem Cells - drug effects
Stem Cells - metabolism
Suramin - pharmacology
Tibia - cytology
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Summary:Extracellular nucleotides have multiple biological actions in processes such as proliferation, differentiation, chemotaxis, and cytokine secretion through P2X receptors on the cell surface. To determine the biological activity of adenosine triphosphate (ATP) and the expression of P2 nucleotide receptors in murine bone marrow-derived hematopoietic cells and stem cells/progenitor cells, we investigated the effects of ATP in assays of cell proliferation and cell death in vitro. Our results demonstrated that several subtypes of P2X receptors were expressed on hematopoietic cells and that P2X7, in particular, was partially expressed in hematopoietic stem cells/progenitor cells. In addition, stimulation of hematopoietic cells with high concentrations of ATP caused severe inhibition of cell proliferation despite the presence of cytokine stimulation. We analyzed the apoptotic effects of stimulation with several different dosages of ATP and confirmed the enhanced apoptotic activity in hematopoietic cells and progenitor cells. Antagonists, against P2X receptors and ATP, suramin and oxidized ATP, inhibited the induction of cell death for murine hematopoietic cells. Our data suggest that extracellular nucleotides may provide a novel and powerful tool for regulating the cell fate of hematopoietic stem cells.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.30.671