In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 279, No. 2 ( 2000-08-01), p. C510-C519
Abstract:
In human osteoblast-like MG-63 cells, extracellular ATP increased [ 3 H]thymidine incorporation and cell proliferation and synergistically enhanced platelet-derived growth factor- or insulin-like growth factor I-induced [ 3 H]thymidine incorporation. ATP-induced [ 3 H]thymidine incorporation was mimicked by the nonhydrolyzable ATP analogs adenosine 5′- O-(3-thiotriphosphate) and adenosine 5′-adenylylimidodiphosphate and was inhibited by the P2 purinoceptor antagonist suramin, suggesting involvement of P2 purinoceptors. The P2Y receptor agonist UTP and UDP and a P2Y receptor antagonist reactive blue 2 did not affect [ 3 H]thymidine incorporation, whereas the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2′,4-disulfonic acid inhibited ATP-induced [ 3 H]thymidine incorporation, suggesting that ATP-induced DNA synthesis was mediated by P2X receptors. RT-PCR analysis revealed that MG-63 cells expressed P2X 4 , P2X 5 , P2X 6 , and P2X 7 , but not P2X 1 , P2X 2 , and P2X 3 , receptors. In fura 2-loaded cells, not only ATP, but also UTP, increased intracellular Ca 2+ concentration, and inhibitors for several Ca 2+ -activated protein kinases had no effect on ATP-induced DNA synthesis, suggesting that an increase in intracellular Ca 2+ concentration is not indispensable for ATP-induced DNA synthesis. ATP increased mitogen-activated protein kinase activity in a Ca 2+ -independent manner and synergistically enhanced platelet-derived growth factor- or insulin-like growth factor I-induced kinase activity. Furthermore, the mitogen-activated protein kinase kinase inhibitor PD-98059 totally abolished ATP-induced DNA synthesis. We conclude that ATP increases DNA synthesis and enhances the proliferative effects of growth factors through P2X receptors by activating a mitogen-activated protein kinase pathway.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.2000.279.2.C510
Language:
English
Publisher:
American Physiological Society
Publication Date:
2000
detail.hit.zdb_id:
1477334-X
SSG:
12
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