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

点击翻译按钮获取中文摘要

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.