连接蛋白 43 通过 Ca2+ 依赖性 PI3K/Akt 信号通路防止辐射诱发的肠道损伤

IF 2.5 3区 医学 Q2 BIOLOGY
Wilhelmina E Radstake, Alessio Parisi, Janet M Denbeigh, Keith M Furutani, Chris J Beltran
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引用次数: 0

摘要

放疗引起的肠道损伤(RIID)是腹盆腔恶性肿瘤患者放疗的常见副作用。缝隙连接是由连接蛋白(Cxs)组成的特殊结构。本研究旨在探讨附件蛋白在 RIID 中的表达和作用及其内在机制。本研究使用钙黄绿素-AM荧光探针检测肠上皮IEC-6细胞中细胞间隙连接通讯的变化。我们的结果表明,IEC-6细胞在辐照后6、12、24和48小时的细胞间隙连接通讯减少,其中24小时的影响最明显。Western印迹和免疫荧光结果显示,辐照后的肠上皮细胞中Cx43的表达减少,而其他连接蛋白的表达没有减少。沉默 Cx43 会降低辐照肠上皮细胞间隙连接的细胞间通讯,并增加 ROS 和细胞内 Ca2+ 水平。此外,敲除 Cx43 会减少克隆集群的数量,降低细胞增殖,增加细胞毒性和凋亡。Western blotting 结果显示,沉默 Cx43 会导致辐照肠上皮细胞中的γ-H2AX 和 PI3K/AKT 通路蛋白发生变化。服用 PI3K/AKT 通路抑制剂 LY294002 可抑制 Cx43 高表达肠上皮细胞的辐射保护作用。我们的研究表明,电离辐射会降低Cx43的表达,从而促进肠上皮细胞的放射保护作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNA Double-Strand Break Repair Kinetics after Exposure to Photons and Ions: A Systematic Review.

This study offers a review of published data on DNA double strand break (DSB) repair kinetics after exposure to ionizing radiation. By compiling a database, which currently includes 285 DNA DSB repair experiments utilizing both photons and ions, we investigate the impact of distinct experimental parameters on the kinetics of DNA DSB repair. Methodological differences and inconsistencies in reporting make the comparison of data generated by different research groups challenging. Nevertheless, by implementing filtering criteria, we can compare repair kinetics obtained with normal and tumor cells derived from human or animal tissues, as well as cells exposed to photons or ions ranging from hydrogen to iron ions. In addition, several repair curves of repair deficient cell lines were included. The study aims to provide researchers with a comprehensive overview of experimental factors that may confound results and emphasize the importance of precise reporting of experimental parameters. Moreover, we identify gaps in the literature that require attention in future studies, aiming to address clinically relevant questions related to radiotherapy. The database can be freely accessed at: https://github.com/weradstake/DRDNA.

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来源期刊
Radiation research
Radiation research 医学-核医学
CiteScore
5.10
自引率
8.80%
发文量
179
审稿时长
1 months
期刊介绍: Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.
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