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。

• 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

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.

我们先前报道说，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，建议辐射引起的旁观者作用具有刺激细胞细胞因子和/或活性氧的潜力。目前的工作旨在检查这两种现象之间的关系，血清因子和旁观者效应的细胞突变性调节。 1.搜索人体血液中的调节因素。我们发现，血清因子对细胞突变性的调节活性在人类志愿者中通过倾斜床休息（BR）改变了。一些蛋白酶活性在BR后血清中也发生了变化。 2.搜索细胞信号分子。 （1）GRP94;通过分析X射线诱导的蛋白酶，将伴侣的一个GRP94中的一个（GRP94）鉴定为介体分子的候选基因。建议通过使用siRNA用于GRP94 mRNA的菌落形成测定的菌落X射线耐药性。 （2）我们还通过分析紫外线诱导的蛋白酶来识别其他伴侣Hsp27。 Hsp27表达时，紫外线照射后去除6-4个照片产物的活性减少。被压制。这一发现表明HSP27参与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，这些血清因子可能具有与旁观者效应相似的分子机制，似乎是通过伴侣（例如GRP94和HSP27）介导的蛋白酶信号传导。

项目成果

Takahashi S., et al.: "Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress : involvement of E-64-sensitive proteases on suppression of UV mutagenicity"Cell Biol.Int.. 27. 53-56 (2003)

Takahashi S. 等人：“暴露于重力变化压力的人类 UVAP-1 细胞中紫外线诱导的蛋白酶活性水平增加：E-64 敏感蛋白酶参与抑制紫外线致突变性”Cell Biol.Int..

Kita K., et al.: "Involvement of Leu-13 in interferon-induced refractoriness of human RSa cells to X-ray cell killing."Radiat.Res.. 160. 302-308 (2003)

Kita K. 等人：“Leu-13 参与干扰素诱导的人 RSa 细胞对 X 射线细胞杀伤的难治性。”Radiat.Res.. 160. 302-308 (2003)

Takahashi S., et al.: "Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress : involvement of E-64-sensitive proteases on suppression of UV mutagenicity"Cell Biol. Int.. (in press).

Takahashi S. 等人：“暴露于重力变化压力的人类 UVAP-1 细胞中紫外线诱导的蛋白酶活性水平增加：E-64 敏感蛋白酶参与抑制紫外线致突变性”Cell Biol。

Chigira S., Sugita K., Sugaya S., Arase Y., Ichinose M., Shirasawa H.Suzuki N.: "Increased expression of the huntington interacting protein-1 gene, in cells from Hutchinson Gilford syndrome (Progeria) patients and aged donors."J.Gerontology : Biological S

Chigira S.、Sugita K.、Sugaya S.、Arase Y.、Ichinose M.、Shirasawa H.Suzuki N.：“Hutchinson Gilford 综合征（早衰症）患者和 Shirasawa H.Suzuki N. 细胞中亨廷顿相互作用蛋白 1 基因的表达增加

Hasegawa, R., et al.: "Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction"J. Lab. Clin. Med.. (in press).

Hasekawa, R., et al.：“急性心肌梗死早期人血清因子诱导细胞凋亡和泛素水解酶基因表达”J.