Heat Shock Factor 1 Deficiency Affects Systemic Body Temperature Regulation
Heat Shock Factor 1 Deficiency Affects Systemic Body Temperature Regulation
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DOI：
10.1159/000441947
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
von Gall, Charlotte
中科院分区：
文献类型：
--
作者：
Ingenwerth, Marc;Noichl, Erik;von Gall, Charlotte
简介：热休克因子1（HSF 1）是一种普遍存在的热敏性转录因子，其介导热休克蛋白的转录以响应细胞应激，例如升高的温度，从而保护生物体免受错误折叠蛋白的侵害。在这项研究中，我们分析了HSF 1缺乏对核心体温调节的影响。材料和方法：记录野生型小鼠和HSF 1缺陷型小鼠的体温、自发活动和摄食量。催乳素和促甲状腺激素水平测定ELISA法。通过定量实时PCR分析棕色脂肪组织中的基因表达。使用共聚焦激光扫描显微镜分析下丘脑HSF1及其与酪氨酸羟化酶的共定位。结果如下：HSF1缺陷小鼠表现出核心体温升高（体温过高），整体运动活动减少，垂体和血浆中催乳素水平降低，这让人联想到冷适应。HSF1在下丘脑参与体温调节的不同区域均有表达，提示HSF1在下丘脑体温调节中具有潜在的作用。此外，HSF1与多巴胺合成的限速酶酪氨酸羟化酶共定位，表明HSF1在下丘脑控制催乳素释放中的潜在作用。在棕色脂肪组织中，HSF1缺陷小鼠的催乳素受体和解偶联蛋白1的水平增加，与产热的上调一致。结论：我们的数据表明，热休克因子1在全身温度调节的作用。(C)2015 S. Karger AG，巴塞尔
Introduction: Heat shock factor 1 (HSF1) is a ubiquitous heat-sensitive transcription factor that mediates heat shock protein transcription in response to cellular stress, such as increased temperature, in order to protect the organism against misfolded proteins. In this study, we analysed the effect of HSF1 deficiency on core body temperature regulation. Materials and Methods: Body temperature, locomotor activity, and food consumption of wild-type mice and HSF1-deficient mice were recorded. Prolactin and thyroid-stimulating hormone levels were measured by ELISA. Gene expression in brown adipose tissue was analysed by quantitative real-time PCR. Hypothalamic HSF1 and its co-localisation with tyrosine hydroxylase was analysed using confocal laser scanning microscopy. Results: HSF1-deficient mice showed an increase in core body temperature (hyperthermia), decreased overall locomotor activity, and decreased levels of prolactin in pituitary and blood plasma reminiscent of cold adaptation. HSF1 could be detected in various hypothalamic regions involved in temperature regulation, suggesting a potential role of HSF1 in hypothalamic thermoregulation. Moreover, HSF1 co-localises with tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, suggesting a potential role of HSF1 in the hypothalamic control of prolactin release. In brown adipose tissue, levels of prolactin receptor and uncoupled protein 1 were increased in HSF1-deficient mice, consistent with an up-regulation of heat production. Conclusion: Our data suggest a role of HSF1 in systemic thermoregulation. (C) 2015 S. Karger AG, Basel