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

我们之前报道过，人血清因子对细胞突变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具有刺激细胞因子和/或活性氧的潜力。本工作旨在研究这两种现象之间的关系，细胞突变性的调节血清因子和旁观者效应。1.寻找人体血液中的调节因子。我们发现，头低位卧床（BR）改变了人体血清因子对细胞突变性的调节活性。BR后血清中的一些蛋白酶活性也发生了变化。2.寻找细胞信号分子。(1)GRP 94;伴侣蛋白之一GRP 94通过X射线诱导的蛋白酶分析被鉴定为介体分子的候选基因。通过对GRP 94 mRNA进行siRNA的殖民地形成实验，提示GRP 94参与了细胞的X射线抗性。(2)我们还确定了另一个伴侣，热休克蛋白27，通过分析紫外诱导的蛋白酶。HSP 27的表达降低了紫外线照射后6-4光产物的清除活性。抑制这一发现表明HSP 27参与了细胞的紫外线敏感性。因此，这些血清因子对细胞突变性的调节，可能与旁观者效应具有相似的分子机制，似乎是通过蛋白酶信号传导介导的，如GRP 94和HSP 27。

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.