Cytochrome-c mediated a bystander response dependent on inducible nitric oxide synthase in irradiated hepatoma cells.
Cytochrome-c mediated a bystander response dependent on inducible nitric oxide synthase in irradiated hepatoma cells.
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细胞色素-c 在受辐射的肝癌细胞中介导依赖于诱导型一氧化氮合酶的旁观者反应
DOI：
10.1038/bjc.2012.9
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发表时间：
2012-02-28
影响因子：
8.8
通讯作者：
Shao, C.
中科院分区：
文献类型：
--
作者：
He, M.;Ye, S.;Ren, R.;Dong, C.;Xie, Y.;Yuan, D.;Shao, C.
辐射诱导的旁观者效应（里贝）在肿瘤放射治疗中具有重要意义，但对旁观者信号的研究尚不清楚。通过检测细胞色素c（cyt-c）、诱导型一氧化氮合酶（iNOS）、一氧化氮（NO）和活性氧（ROS）等分子的产生，探讨细胞色素c（cyt-c）和自由基在里贝（RIBE）诱导人肝癌细胞HepG 2微核形成中的作用。当HepG 2细胞与相同数量的受照HepG 2细胞共培养时，未受照的旁观者细胞中MN的产量以依赖于辐射剂量和细胞共培养时间的方式增加，但当细胞用cyt-c释放抑制剂环孢菌素A（CsA）处理时，MN的产量减少。同时CsA处理抑制辐射诱导的NO而不抑制ROS。当细胞共培养液中加入5 μM cyt-c时，CsA抑制的旁观者效应和NO生成均被逆转。但这些外源性cyt-c介导的NO和旁观者MN的过度生产被取消时，细胞用s-甲基异硫脲硫酸盐，iNOS抑制剂预处理。辐射诱导的cyt-c在HepG 2细胞中通过iNOS触发的NO信号而不是ROS调节旁观者反应中具有深远的作用。
Radiation-induced bystander effect (RIBE) has important implication in tumour radiotherapy, but the bystander signals are still not well known. The role of cytochrome-c (cyt-c) and free radicals in RIBE on human hepatoma cells HepG2 was investigated by detecting the formation of bystander micronuclei (MN) and the generation of endogenous cyt-c, inducible nitric oxide (NO) synthase (iNOS), NO, and reactive oxygen species (ROS) molecules. When HepG2 cells were cocultured with an equal number of irradiated HepG2 cells, the yield of MN in the nonirradiated bystander cells was increased in a manner depended on radiation dose and cell coculture time, but it was diminished when the cells were treated with cyclosporin A (CsA), an inhibitor of cyt-c release. Meanwhile the CsA treatment inhibited radiation-induced NO but not ROS. Both of the depressed bystander effect and NO generation in the CsA-treated cells were reversed when 5 μM cyt-c was added in the cell coculture medium. But these exogenous cyt-c-mediated overproductions of NO and bystander MN were abolished when the cells were pretreated with s-methylisothiourea sulphate, an iNOS inhibitor. Radiation-induced cyt-c has a profound role in regulating bystander response through an iNOS-triggered NO signal but not ROS in HepG2 cells.
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影响因子：
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