相关实验视频
Updated: Jul 1, 2025

Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
纯能信号传递促进了过早衰老的发生
Daniela Volonte1, Cory J Benson2, Stephanie L Daugherty1
1Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
细胞外ATP触发P2Y11受体的激活,导致释放和反应性氧物种的产生,导致过早的肺纤维细胞衰老. 这一过程促进了三阴性乳腺癌细胞的增殖.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 癌症研究 癌症研究
背景情况:
- 细胞外ATP通过P2纯能受体发出信号.
- 纯能信号传递与细胞衰老之间的联系尚未得到充分理解.
- 细胞衰老在衰老和癌症发展中起着重要作用.
研究的目的:
- 研究细胞外ATP和P2受体在细胞衰老中的作用.
- 为了阐明参与ATP诱导衰老的信号通路.
- 为了确定衰老的肺纤维细胞是否促进癌细胞增殖.
主要方法:
- 使用氧化应激和外源ATP诱导人类肺纤维细胞的衰老.
- 药理上抑制和激活P2Y11受体 (P2Y11R).
- 测量细胞内 (Ca++) 水平,反应性氧物种 (ROS) 生产和细胞增殖.
主要成果:
- 氧化应激诱导ATP释放和衰老;P2受体抑制减少了衰老.
- P2Y11R激活对ATP诱导的衰老至关重要,涉及从ER释放Ca++以及随后的线粒体Ca++过载.
- 衰老的肺纤维细胞分泌安菲瑞古林,促进三阴性乳腺癌细胞的增殖和瘤发生.
结论:
- 通过P2Y11R,细胞外ATP通过ER-线粒体信号传递和ROS产生,诱导肺纤维细胞的过早衰老.
- 这种ATP诱导的衰老创造了一个原始原始微环境,增强了癌细胞的生长.
- 这项研究揭示了一种新的纯能信号通路,将ATP与一种亲瘤起源的衰老表型联系起来.
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