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The relationship between molecular mechanisms of serum factors and bystander effects modulating cell mutability.

血清因子的分子机制与旁观者效应调节细胞突变性之间的关系。

基本信息

批准号：
14580561
负责人：
SUZUKI Nobuo
金额：
$ 2.3万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580561/
关键词：
GENE MUTATION HUMAN CELL HUMAN SERUM BYSTANDER EFFECT CHAPERON ULTRAVIOLET RAY X-RAY DNA REPAIR

项目摘要

We previously reported that modulation of cell mutability by human serum factors is associated with increased levels of protease activity. However, radiation-induced bystander effects are suggested to have the potential to stimulate cellular cytokines and/or reactive oxygen species. The present work is designed to examine the relationships between these two phenomena, cell mutability modulation by serum factors and bystander effects. 1.A search for modulating factors in human blood. We found that the modulating activity of serum factors on cell mutability was changed in human volunteer by Head-down-tilt bed rest (BR). Some protease activities were also changed in post-BR serum. 2.A search for cellular signaling molecules. (1) GRP94; One, of the chaperons, GRP94, was identified as a candidate gene for the mediator molecule by analysis of X-ray-induced protease. GRP94 was suggested to be involved in cellular X-ray resistance by the colony forming assay using siRNA for GRP94 mRNA. (2) We also identified the other chaperon, HSP27, by analysis of UV-induced protease. The activity of removing 6-4 photo products after UV irradiation was decreased when expression of HSP27 was. suppressed. This finding indicates that HSP27 is involved in the UV susceptibility of cells. Thus, the modulation of cell mutability by these serum factors, which may have similar molecular mechanisms to bystander effects, seems to be mediated though protease signaling by chaperons such as GRP94 and HSP27.

我们以前报道过，人血清因子对细胞变异性的调节与蛋白酶活性水平的增加有关。然而，辐射诱导的旁观者效应被认为有可能刺激细胞因子和/或活性氧。目前的工作旨在检查这两种现象之间的关系，细胞突变调节的血清因子和旁观者效应。1.对人体血液中调节因子的研究。我们发现，受试者在头-下倾斜卧床后，血清因子对细胞突变的调节活性发生了变化。br后血清中一些蛋白酶活性也发生了变化。2.对细胞信号分子的研究。(1) GRP94;通过对x射线诱导蛋白酶的分析，其中一个伴侣子GRP94被鉴定为中介分子的候选基因。利用siRNA对GRP94 mRNA进行集落形成实验，提示GRP94参与细胞x射线抗性。(2)通过对紫外光诱导蛋白酶的分析，我们还鉴定出了另一个伴侣子HSP27。当HSP27表达量增加时，紫外线照射后6-4光产物的去除活性降低。抑制。这一发现表明HSP27参与了细胞对紫外线的敏感性。因此，这些血清因子对细胞易变性的调节，可能具有与旁观者效应相似的分子机制，似乎是通过GRP94和HSP27等伴侣的蛋白酶信号传导介导的。