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Induction of heat shock gene expression in RAT1 primary fibroblast cells by ELF electric fields

机译:ELF电场诱导RAT1原代成纤维细胞热休克基因表达

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摘要

Recent studies have demonstrated that the Ku70 gene fragment can be placed in the anti-sense orientation under the control of a heat-inducible heat shock protein 70 (HSP70) promoter and activated through heat shock exposure. This results in attenuation of the Ku70 protein expression, inhibiting cellular repair processes, and sensitizing the transfected cells to exposures such as the ionizing radiation exposures used clinically. However, achieving the tissue temperatures necessary to thermally induce the HSP70 response presents significant limitations to the clinical application of this strategy. Previous findings suggest an alternative approach to inducing a heat shock response, specifically through the use of extremely low frequency (ELF) electrical field stimulation. To further pursue this approach, we investigated HSP70 responses in transfected rat primary fibroblast (RAT1) cells exposed to 10Hz electric fields at intensities of 20-500V/m. We confirmed that low frequency electric fields can induce HSP70 heat shock expression, with peak responses obtained at 8h following a 2h field exposure. However, the approximate threefold increase in expression is substantially lower than that obtained using thermal stimulation, raising questions of the clinical utility of the response.
机译:最近的研究表明,Ku70基因片段可以在热诱导热休克蛋白70(HSP70)启动子的控制下置于反义取向,并通过热休克暴露被激活。这导致 Ku70 蛋白表达减弱,抑制细胞修复过程,并使转染细胞对暴露敏感,例如临床使用的电离辐射暴露。然而,达到热诱导 HSP70 反应所需的组织温度对该策略的临床应用存在重大限制。先前的研究结果提出了一种诱导热休克反应的替代方法,特别是通过使用极低频 (ELF) 电场刺激。为了进一步研究这种方法,我们研究了暴露于10-20V/m强度的10Hz电场的转染大鼠原代成纤维细胞(RAT1)细胞中的HSP50反应。我们证实低频电场可以诱导 HSP70 热休克表达,在 2 小时场暴露后 8 小时获得峰值响应。然而,表达的大约三倍的增加大大低于使用热刺激获得的增加,这引发了对反应的临床效用的质疑。

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