Mitochondria-dependent signalling pathway are involved in the early process of radiation-induced bystander effects.
Mitochondria-dependent signalling pathway are involved in the early process of radiation-induced bystander effects.
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DOI：
10.1038/sj.bjc.6604358
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发表时间：
2008-06-03
影响因子：
8.8
通讯作者：
Wu, L.
中科院分区：
文献类型：
--
作者：
Chen, S.;Zhao, Y.;Han, W.;Zhao, G.;Zhu, L.;Wang, J.;Bao, L.;Jiang, E.;Xu, A.;Hei, T. K.;Yu, Z.;Wu, L.
细胞质照射诱导的旁观者效应近年来已有报道。然而，潜在的机制，如线粒体的功能作用，尚不清楚。在本研究中，我们使用线粒体DNA缺失的（ρ0）AL或正常（ρ+）AL细胞作为辐射供体细胞，正常人皮肤成纤维细胞作为受体细胞，在一系列的培养基转移实验中研究了辐射相关的信号过程。我们的研究结果表明，线粒体呼吸链功能抑制剂处理的线粒体DNA缺失的细胞或正常AL细胞具有减弱的γ-H2 AX诱导，这表明线粒体在旁观者效应中发挥功能性作用。此外，研究发现，用特异性NOS抑制剂或线粒体钙摄取抑制剂（钌红）处理正常AL供体细胞可显著降低γ-H2 AX诱导，辐射可刺激受辐射的ρ+ AL细胞产生NO和O2·−，但在ρ0 AL细胞中则不然。这些观察结果，以及钌红处理显著降低辐射ρ+ AL细胞中NO和O2·−水平的发现，表明辐射诱导的线粒体NO可能是细胞内的旁观者因子，并且钙依赖性线粒体NOS可能在该过程中起重要作用。
Bystander effects induced by cytoplasmic irradiation have been reported recently. However, the mechanism(s) underlying, such as the functional role of mitochondria, is not clear. In the present study, we used either mtDNA-depleted (ρ0) AL or normal (ρ+) AL cells as irradiated donor cells and normal human skin fibroblasts as receptor cells in a series of medium transfer experiments to investigate the mitochondria-related signal process. Our results indicated that mtDNA-depleted cells or normal AL cells treated with mitochondrial respiratory chain function inhibitors had an attenuated γ-H2AX induction, which indicates that mitochondria play a functional role in bystander effects. Moreover, it was found that treatment of normal AL donor cells with specific inhibitors of NOS, or inhibitor of mitochondrial calcium uptake (ruthenium red) significantly decreased γ-H2AX induction and that radiation could stimulate cellular NO and O2•− production in irradiated ρ+ AL cells, but not in ρ0 AL cells. These observations, together with the findings that ruthenium red treatment significantly reduced the NO and O2•− levels in irradiated ρ+ AL cells, suggest that radiation-induced NO derived from mitochondria might be an intracellular bystander factor and calcium-dependent mitochondrial NOS might play an essential role in the process.
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DOI：
10.1006/bbrc.1996.0008
发表时间：
1996-01-05
影响因子：
3.1
作者：
Bates, TE;Loesch, A;Clark, JB
通讯作者：
Clark, JB
影响因子：
8
作者：
Burdak-Rothkamm, S.;Short, S. C.;Prise, K. M.
通讯作者：
Prise, K. M.
影响因子：
3.4
作者：
Wan, XS;Zhou, ZZ;Kennedy, AR
通讯作者：
Kennedy, AR
DOI：
10.1152/ajpheart.00737.2003
发表时间：
2004-01-01
影响因子：
4.8
作者：
Kanai, A;Epperly, M;Peterson, J
通讯作者：
Peterson, J
DOI：
10.1073/pnas.011417098
发表时间：
2001-01-16
影响因子：
11.1
作者：
Azzam, EI;de Toledo, SM;Little, JB
通讯作者：
Little, JB