热休克因子1活性的调控机制

热休克因子1(HSF1)是调控热休克蛋白(HSPs)表达的核心转录因子,可被热应激、氧化应激、缺氧/血、pH下降等刺激因素激活,与靶基因的热休克元件特异性结合,增强HSPs表达,发挥内源性保护作用.HSF1活性的调控发生在HSF1三聚化、转位入核、结合DNA和调节转录等多个环节,受到分子伴侣蛋白、磷酸化作用、氧化-还原等机制共同调控,其复杂而精确的调控对于应激应答、生长发育等过程有重要意义.     

热休克蛋白的生物学作用和转录水平调控研究进展(英文)

热休克蛋白 (HSP)具有广泛的生物学功能 ,其表达方式有两种 :一种是诱导性表达 ,即当生物、细胞受到刺激时才进行表达 ;另一种是组成性表达 ,即在生物、细胞的正常生活、代谢过程中表达。HSP的这两种表达方式意味着HSP基因表达的调控方式和机理不同。本文简要介绍了热休克因子(HSF)的种类、结构及调控HSP基因表达的机理。HSF通过以下 4个步骤调节HSP基因表达 :( 1 )HSF由单体形式变成磷酸化的三聚体形式被激活 ;( 2 )三聚体形式的HSF与HSP基因的热休克元件(HSE)上相邻排列的 3个 5′ GAA 3′结合 ;( 3)与HSF结合后 ,HSE的活化域暴露 ,HSP基因转录 ;( 4 )HSP的mRNA 5′端前导区的特异结构适合于核糖体快速结合和高效翻译。不同生物体内的HSF作用有一定差异 ,功能较为明确的有 :( 1 )对应激信号敏感的HSF1 ;( 2 )对应激信号不敏感 ,对生长、发育、分化信号敏感的HSF2 ;( 3)起抑制HSP基因转录作用的HSF4。还有一些HSF(如HSF3)的作用机制较复杂 ,有待深入研究。此外 ,本文也简要介绍了HSP在衰老、免疫应答、细胞生存和凋亡平衡等中的作用 ,对了解和认识生物生长、发育、衰老、保护、免疫应答及细胞生存和凋亡平衡的分子机制有一定帮助。     

热休克蛋白的生物学作用和转录水平调控研究进展

热休克蛋白（HSP）具有广泛的生物学功能,其表达方式有两种：一种是诱导性表达,即当生物细胞受到刺激时才进行表达,另一种是组成性表达,即在生物,细胞的正常生活,代谢过程中表达。HSP的这两种表达式意味着HSP基因表达的调控方式和机理不同。本文简要介绍了热休克因子（HSF）的种类,结构及调控HSP基因表达的机理,HSF通过以下4个步骤调节HSP基因：（1）HSF由单体形式变成磷酸化的三聚体形式被激活;（2）三聚体形成式的HSF与HSP基因的热休克元件（HSE）上相邻排列的3个5′－GAA－3′结合,（3）与HSF结合后,HSE的活化域暴露,HSP基因转录;（4）HSP的mRNA5′端前导芪的特异结构适合于核糖体快速结合和高效翻译,不同生物体内的HSF作用有一定差异,功能较为明确的有：（1）对应激信号敏感的HSF1;（2）对应激信号不敏感,对生长,发育,分化信号敏感的HSF2;（3）起抑制HSP基因转录作用的HSF4。还有一些HSF（如HSF3）的作用机制较复杂,有待深入研究。此外,本文也简单介绍了HSP在衰老,免疫应答,细胞生存和凋亡平衡等中的作用,对了解和认识生物生长,发育,衰老,保护,免疫应答及细胞生存和凋亡平衡的分子机制有一定帮助。     

热对成骨和破骨细胞影响及热休克蛋白和因子参与调节的研究进展

热物理因素在骨疾病的治疗、骨再生修复过程中的应用及对成骨细胞影响重要性的认识不断被深化,一定温度热处理可促进成骨细胞分化,热休克蛋白及热休克因子参与细胞保护与分化.但目前尚未阐明热对成骨细胞与破骨细胞偶联关系的影响及热休克蛋白70(HSP70)和热休克因子2(HSF2)对成骨细胞RANKL的调节机制.探明该影响及调节机制可能成为揭示热物理干预影响骨转化的关键所在之一.     

热休克转录因子1的抗炎症作用

热休克转录因子1(heat shock factor 1, HSF1)是调节细胞保护性应激蛋白--热休克蛋白表达的主要转录因子,可被热应激、氧化应激等多种理化因素激活.近年研究表明,HSF1具有抗炎症作用:HSF1可抑制TNFα、IL-1β、M-CSF等致炎因子表达,促进IL-10等抗炎因子表达,并降低NF-κB、AP-1等致炎转录因子的活性.HSF1上调热休克蛋白和抑制炎症的双重活性,提示其很可能是联系应激反应和炎症反应的重要因子.     

人热休克因子1突变体的应用研究进展

热休克因子1是调节应激反应的主要转录因子,它在应激条件下可被活化。通过基因突变得到正显性和负显性热休克因子1,它们不需要外界条件刺激就分别具有启动热休克蛋白的表达或竞争抑制内源热休克因子1活性的能力。目前,已有多个热休克因子1的突变体应用于疾病研究。介绍了热休克因子1的结构和活化途径,以及热休克因子1突变体在肿瘤、神经系统及心血管系统等方面的应用进展。     

人热休克因子1突变体的应用研究进展

热休克因子1是调节应激反应的主要转录因子,它在应激条件下可被活化。通过基因突变得到正显性和负显性热休克因子1,它们不需要外界条件刺激就分别具有启动热休克蛋白的表达或竞争抑制内源热休克因子1活性的能力。目前,已有多个热休克因子1的突变体应用于疾病研究。介绍了热休克因子1的结构和活化途径,以及热休克因子1突变体在肿瘤、神经系统及心血管系统等方面的应用进展。     

热休克蛋白调控机制

热休克蛋白是生物体体应对温度、pH、渗透压等不利环境刺激时合成的一种保护蛋白。在环境应激时,调控因子可以在转录水平上调控热休克基因的表达,恢复或加速清除细胞内已经变性的蛋白质,使细胞处于稳态并产生耐受性。大量研究发现,热休克调控因子对微生物应激耐受性发挥重要作用,具有广阔的应用前景。综述了6类热休克调控因子的调控机制以及相互作用,对调控因子HrcA、σ^B和CtsR进行了重点阐述,旨在为进一步构建热休克调控网络提供有价值的参考。     

热休克蛋白27和热休克因子1在子痫前期胎盘表达及意义

目的:研究热休克蛋白27(heat shock protein 27,HSP27)与热休克因子l(heat shock factor 1,HSFl)在子痫前期孕妇胎盘中的表达情况.方法:选择2011年6月-2012年6月在南京医科大学第一附属医院产科住院分娩的子痫前期患者21例(子痫前期组),以同期分娩的正常孕妇21例(正常妊娠组)作为对照组,采用实时定量聚合酶链反应(RT-PCR)、免疫组化(Immunohistochemistry)、蛋白印迹法(Western Blotting)检测两组孕妇胎盘HSP27mRNA和蛋白的表达以及HSF1蛋白表达水平,分析其是否存在组间差异.结果:子痫前期组胎盘中HSP27mRNA表达(3.28±0.34)高于正常妊娠组(1.87±0.22)和蛋白的表达明显增高,HSF1蛋白表达增高,差异具有统计学意义;HSF1与HSP27呈正相关关系(r=0.73,P＜0.05).结论:胎盘中HSF1是HSP27表达的主要调控因子.     

CHIP interacts with heat shock factor 1 during heat stress

Heat shock factor 1 (HSF1) is a major transactivator of heat shock genes in response to stress and mediates cell protection against various harmful conditions. In this study, we identified the interaction of CHIP (carboxyl terminus of the heat shock cognate protein 70-interacting protein) with the N-terminus of HSF1. Using GST full-down assay, we found that CHIP directly interacts with C-terminal deleted HSF1 (a.a. 1-290) but not with full-length HSF1 under non-stressed conditions. Interestingly, interaction of CHIP with full-length HSF1 was induced by heat shock treatment. The structural change of HSF1 was observed under heat stressed conditions by CD spectra. These observations demonstrate the direct interaction between HSF1 and CHIP and this interaction requires conformational change of HSF1 by heat stress.     

The maximal cytoprotective function of the heat shock protein 27 is dependent on heat shock protein 70

Endogenous heat shock proteins (HSPs) 70 and 25/27 are induced in renal cells by injury from energy depletion. Transfected over-expression of HSPs 70 or 27 (human analogue of HSP25), provide protection against renal cell injury from ATP deprivation. This study examines whether over-expressed HSP27 depends on induction of endogenous HSPs, in particular HSP70, to afford protection against cell injury. LLC-PK1 cells transfected with HSP27 (27OE cells) were injured by ATP depletion for 2 h and recovered for 4 h in the presence of HSF decoy, HSP70 specific siRNA (siRNA-70) and their respective controls. Injury in the presence of HSF decoy, a synthetic oligonucleotide identical to the heat shock element, the nuclear binding site of HSF, decreased HSP70 induction by 80% without affecting the over-expression of transfected HSP27. The HSP70 stress response was completely ablated in the presence of siRNA-70. Protection against injury, provided by over-expression of HSP27, was reduced by treatment with HSF decoy and abolished by treatment with siRNA-70. Immunoprecipitation studies demonstrated association of HSP27 with actin that was not affected by either treatment with HSF decoy or siRNA. Therefore, HSP27 is dependent on HSP70 to provide its maximal cytoprotective effect, but not for its interaction with actin. This study suggests that, while it has specific action on the cytoskeleton, HSP 25/27 must have coordinated activity with other HSP classes, especially HSP70, to provide the full extent of resistance to injury from energy depletion.     

Bicyclol: a novel antihepatitis drug with hepatic heat shock protein 27/70-inducing activity and cytoprotective effects in mice

Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.