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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| Veröffentlicht in: | Biological & Pharmaceutical Bulletin 2007, Vol.30(4), pp.671-676 |
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| creator | Yoon, Mi-Jung Lee, Hyun-Joo Lee, Yong-Soo Kim, Jae-Hwan Park, Jin-Ki Chang, Won-Kyong Shin, Ho-Chul Kim, Dong-Ku |
| description | 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. |
| doi_str_mv | 10.1248/bpb.30.671 |
| format | Article |
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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.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.30.671</identifier><identifier>PMID: 17409500</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>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</subject><ispartof>Biological and Pharmaceutical Bulletin, 2007, Vol.30(4), pp.671-676</ispartof><rights>2007 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c684t-33d9a9aa25083ef456fe3c3d780cb7c0e3f4a8e135bf9a37113e696d21128f1c3</citedby><cites>FETCH-LOGICAL-c684t-33d9a9aa25083ef456fe3c3d780cb7c0e3f4a8e135bf9a37113e696d21128f1c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,1884,27928,27929</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17409500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoon, Mi-Jung</creatorcontrib><creatorcontrib>Lee, Hyun-Joo</creatorcontrib><creatorcontrib>Lee, Yong-Soo</creatorcontrib><creatorcontrib>Kim, Jae-Hwan</creatorcontrib><creatorcontrib>Park, Jin-Ki</creatorcontrib><creatorcontrib>Chang, Won-Kyong</creatorcontrib><creatorcontrib>Shin, Ho-Chul</creatorcontrib><creatorcontrib>Kim, Dong-Ku</creatorcontrib><creatorcontrib>Konkuk University</creatorcontrib><creatorcontrib>aCell and Gene Therapy Research Institute</creatorcontrib><creatorcontrib>National Livestock Research Institute</creatorcontrib><creatorcontrib>bAnimal Biotechnology Division</creatorcontrib><creatorcontrib>Pochon CHA University</creatorcontrib><creatorcontrib>RDA</creatorcontrib><creatorcontrib>cDepartment of Veterinary Pharmacology and Toxicology</creatorcontrib><creatorcontrib>Graduate School of Life Science and Biotechnology</creatorcontrib><creatorcontrib>CHA General Hospital</creatorcontrib><creatorcontrib>College of Veterinary Medicine</creatorcontrib><title>Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells</title><title>Biological & Pharmaceutical Bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>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.</description><subject>Adenosine Triphosphate - analogs & derivatives</subject><subject>Adenosine Triphosphate - pharmacology</subject><subject>Animals</subject><subject>antagonis</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>ATP</subject><subject>Bone Marrow Cells</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Dose-Response Relationship, Drug</subject><subject>Femur - cytology</subject><subject>hematopoietic stem cell</subject><subject>Hematopoietic System - cytology</subject><subject>Hematopoietic System - drug effects</subject><subject>Hematopoietic System - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>P2X</subject><subject>proliferation</subject><subject>Purinergic P2 Receptor Antagonists</subject><subject>Receptors, Purinergic P2 - metabolism</subject><subject>Receptors, Purinergic P2X</subject><subject>Stem Cells - drug effects</subject><subject>Stem Cells - metabolism</subject><subject>Suramin - pharmacology</subject><subject>Tibia - cytology</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1r3DAQhkVpabZpL_0BxVDIoeDtjD78cSrLkjQLKe0hPfQkZHncaPFarmSH9t9XZjcJ5DJCvM-8M3rF2HuENXJZfW7GZi1gXZT4gq1QyDJXHNVLtoIaq7xAVZ2xNzHuAaAELl6zMywl1ApgxX5d_p2CsdT3c29Ctrn9ke1ithvufX9PbeaGbLqjdG9nOzk_ZL7LNqMfJx9dXNRvc3ADZdd0MJMfvaPJ2Wyb7OJb9qozfaR3p_Oc_by6vN1e5zffv-62m5vcFpWcciHa2tTGcAWVoE6qoiNhRVtWYJvSAolOmopQqKarjSgRBRV10XJEXnVoxTm7OPqOwf-ZKU764OLyIDOQn6MuQShegUrgx2fg3s9hSLtplLIWBSgoEvXpSNngYwzU6TG4gwn_NIJe4tYpbi1Ap7gT_OFkOTcHap_QU74JuDoCSXXW9H7oU1xPg20sG-d7r3n6G50aAKQGRA3JfikFcl7zOhl9ORrt42R-0-MkE1LgPT0sJY9laX5Q7J0JmgbxHywApqk</recordid><startdate>20070401</startdate><enddate>20070401</enddate><creator>Yoon, Mi-Jung</creator><creator>Lee, Hyun-Joo</creator><creator>Lee, Yong-Soo</creator><creator>Kim, Jae-Hwan</creator><creator>Park, Jin-Ki</creator><creator>Chang, Won-Kyong</creator><creator>Shin, Ho-Chul</creator><creator>Kim, Dong-Ku</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070401</creationdate><title>Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells</title><author>Yoon, Mi-Jung ; 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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. 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| 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 |
| title | Extracellular ATP Is Involved in the Induction of Apoptosis in Murine Hematopoietic Cells |
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