期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1800, 期 1, 页码 40-46出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2009.10.008
关键词
ionizing irradiation; ATP release; P2X(7) receptor
资金
- Strategic Promotion Program for Basic Nuclear Research [200305]
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [19790097]
- The Japan Science Society [19-419]
Background: Ionizing irradiation causes not only growth arrest and cell death, but also release of growth factors or signal transmitters, which promote cancer malignancy. Extracellular ATP controls cancer growth through activation of purinoceptors. However, there is no report of radiation-induced ATP release from cancer cells. Here, we examined gamma-irradiation-induced ATP release and its mechanism in B16 melanoma. Methods: Extracellular ATP was measured by luciferin-luciferase assay. To investigate mechanism of radiation-induced ATP release, we pharmacologically inhibited the ATP release and established stable P2X(7) receptor-knockdown B16 melanoma cells using two short hairpin RNAs targeting P2X(7) receptor. Results: Cells were exposed to 0.5-8 Gy of gamma-rays. Extracellular ATP was increased, peaking at 5 min after 0.5 Gy irradiation. A selective P2X(7) receptor channel antagonist, but not anion transporter inhibitors, blocked the release of ATP. Further, radiation-induced ATP release was significantly decreased in P2X(7) receptor-knockdown cells. Our results indicate that gamma-irradiation evokes ATP release from melanoma cells, and P2X(7) receptor channel plays a significant role in mediating the ATP release. General Significance: We suggest that extracellular ATP could be a novel intercellular signaling molecule released from cancer cells when cells are exposed to ionizing radiation. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据