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首页> 外文期刊>Journal of Cell Communication and Signaling >Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro
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Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro

机译：轻度和重度应激对人皮肤成纤维细胞体外老化后热休克因子-1的差异转运

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摘要

Repeated exposure to mild heat shock (HS) has been shown to induce a wide range of health promoting hormetic effects in various biological systems, including human cells undergoing aging in vitro. In order to understand how cells distinguish between mild and severe stress, we have investigated the extent of early and immediate HS response by analyzing the nuclear translocation of the transcription factor heat shock factor-1 (HSF1), in serially passaged normal adult human facial skin fibroblasts exposed to mild (41 °C) or severe (43 °C) HS. Cells respond differently when exposed to mild and severe HS at different passage levels in terms of the extent of HSF1 translocation. In early passage young cells there was a 5-fold difference between mild and severe HS in the extent of HSF1 translocation. However, in near senescent late passage cells, the difference between mild and severe stress in terms of the extent of HSF1 translocation was reduced to less than 2-fold. One of the reasons for this agerelated attenuation of heat shock response is due to the fact there was a higher basal level of HSF1 in the nuclei of late passage cells, which is indicative of increased intrinsic stress during cellular aging. These observations are consistent with previously reported data that whereas repeated mild stress given at younger ages can slow down aging and increase the lifespan, the same level of stress given at older ages may not provide the same benefits. Therefore, elucidating the early and immediate steps in the induction of stress response can be useful in deciding whether a particular level of stress is potentially hormetically beneficial or not.
机译：研究表明，反复暴露于轻度热休克（HS）会在各种生物系统（包括正在体外老化的人体细胞）中诱导多种促进健康的造福效应。为了了解细胞如何区分轻度和重度压力，我们通过分析连续传代的正常成年人面部皮肤中转录因子热休克因子-1（HSF1）的核易位，研究了早期和即时HS反应的程度。成纤维细胞暴露于轻度（41°C）或重度（43°C）HS。就HSF1易位的程度而言，当暴露于不同传代水平的轻度和重度HS时，细胞的反应不同。在早期传代的年轻细胞中，HSF1易位的程度在轻度和重度HS之间有5倍的差异。但是，在近衰老的晚期传代细胞中，轻度和重度应激之间的差异（就HSF1易位程度而言）已减少到不足2倍。这种与年龄相关的热休克反应减弱的原因之一是由于以下事实：晚期传代细胞核中HSF1的基础水平较高，这表明细胞衰老过程中固有压力增加。这些观察结果与以前报道的数据一致，尽管在年轻时反复施加轻度压力可以减缓衰老并延长寿命，但在老龄时施加相同的压力水平可能无法提供相同的益处。因此，阐明诱导压力反应的早期步骤和立即步骤可能有助于确定特定水平的压力是否可能在造福方面有益。

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