热休克蛋白27在脑缺血耐受中的作用

热休克蛋白27( heat shock protein 27,HSP27)是小分子热休克蛋白家族成员之一,其分子伴侣功能以及与细胞死亡通路的相互作用介导了应激状态下的细胞存活.脑缺血时,缺血灶以及远隔区域HSP27表达量及其磷酸化水平变化与神经元对缺血的耐受性有关.然而,HSP27在脑缺血耐受中的神经保护机制至今尚不完...     

热休克蛋白27/60在胃癌中的表达及意义

目的研究热休克蛋白27和60(HSP27/60)在胃癌组织中的表达及与胃癌生物学行为关系。方法采用免疫组化SABC法检测48例胃癌组织中热休克蛋白27和60的蛋白表达。结果胃癌组织中HSP27和HSP60蛋白表达阳性率分别为64.6%、81.3%;HSP27在胃癌中表达与肿瘤有无远处转移、淋巴结转移个数及浸润深度有关;HSP60表达与肿瘤细胞分化程度及Ki-67增殖指数有关;HSP27/60的表达存在相关性。结论 HSP27/60表达与胃癌生物学行为有相关性,在胃癌的发生、发展过程中发挥着重要的作用。     

大肠癌潜在标志物-热休克蛋白27

目的:探讨大肠癌特异性标志物,为大肠癌的早期诊断、预后判断和治疗提供帮助,同时为理解大肠癌的发病机制提供线索.方法:收集6例大肠癌患者,应用高灵敏的二维凝胶电泳和MALDI-TOF-MS技术检测出肿瘤黏膜和邻近正常结肠黏膜之间差异表达的蛋白.对其中之一热休克蛋白27(HSP27)进行Western blot和免疫组织化学验证.结果:筛选出42个具有明显表达差异的蛋白质点,质谱鉴定出10个差异表达蛋白,包括HSP27、二硫异构酶、核不均一核糖核蛋白A2/B1、磷酸丙糖异构酶、丙酮酸激酶等.Western blot和免疫组织化学结果证实HSP27在大肠癌中有过度表达,提示其可能为重要的肿瘤标志物.结论:大肠癌肿瘤组织与大肠正常黏膜之间存在差异表达蛋白,HSP27在大肠癌中有异常表达,可能作为大肠癌发生、发展的候选生物标志物.     

热休克蛋白70及其在支气管哮喘中的研究进展

热休克蛋白为一类广泛存在于各种生物体的应激蛋白,其高度的保守性及“分子伴侣”功能已为人们所认识。热休克蛋白70为热休克蛋白家族在细胞内含量最多且最保守的一类。近年来,越来越多的研究表明热休克蛋白70在支气管哮喘的免疫及炎症中发挥重要作用,但确切机制尚未明了,仍待进一步的研究探索。     

热休克蛋白20的心血管保护作用

小分子量热休克蛋白是热休克蛋白家族中的一个亚组,不仅仅在机体应激状态,而且在生理状态下也都发挥着重要的生物学作用。热休克蛋白作为其中的一员,在抑制血小板聚集、舒张血管平滑肌、抗细胞凋亡等方面都发挥着重要的作用,从多方面对心血管系统提供保护作用。     

热休克蛋白与胃粘膜病变

热休克蛋白具有保护细胞、抵御外来有害损伤的能力，参与细胞信息传递和基因调控，在胃粘膜病变病理生理中有重要作用，进一步研究热休克蛋白对幽门螺杆菌疫苗 抗肿瘤疫苗研制具有实际价值。     

热休克蛋白70系列与应激性溃疡之间的相互关系

生物细胞在受到各种理化因素刺激后,可以产生一系列的应激反应,诱导热休克蛋白(heat shock protein,HSP)表达.在众多的HSP中,HSP70家族是生物进化过程中最为保守也是目前人们研究最多的一组蛋白.应激可以诱导机体胃黏膜的损伤并可以降低胃黏膜的屏障保护作用,进而导致应激性溃疡的产生,同时加速热休克蛋白的合成,而热休克蛋白反过来又可预防应激性溃疡的发生,抑制胃黏膜细胞凋亡,促进胃溃疡的愈合.本文综述了主要的热休克蛋白分子的分类、调节以及在应激性溃疡中的表达和应用,并简要论述了通过诱导热休克蛋白表达而作为胃黏膜保护剂的几种药物.     

热休克蛋白与胃粘膜病变

热休克蛋白具有保护细胞、抵御外来有害损伤的能力,参与细胞信息传递和基因调控,在胃粘膜病变病理生理中有重要作用,进一步研究热休克蛋白对幽门螺杆菌疫苗和抗肿瘤疫苗研 制具有实际价值。     

血清热休克蛋白70与急性心肌梗死后心力衰竭的相关性

血清热休克蛋白70是一种高度保守的分子蛋白,其在应激时总被高度诱导。研究发现在动脉粥样硬化斑块中有热休克蛋白70的表达,且抗原递呈细胞也高度激活。热休克蛋白70与冠心病密切相关,且与冠状动脉病变程度有关,新近国外研究报道,热休克蛋白70在急性心肌梗死后心力衰竭患者中高度表达。现综述热休克蛋白70与急性心肌梗死后心力衰竭的相关性,热休克蛋白70有望成为急性心肌梗死后心力衰竭的新诊断标记物及判断病情的重要指标。     

热休克蛋白72重组腺病毒包装及其对细胞凋亡的影响

目的 包装热休克蛋白72重组腺病毒表达载体,探讨其对ECV304细胞凋亡的影响.方法采用细菌同源重组法构建了热休克蛋白72重组腺病毒表达载体;流式细胞仪检测重组腺病毒对细胞凋亡的影响;荧光报告系统和蛋白印迹分析重组腺病毒对p53转录的调节和蛋白表达的影响.结果 成功包装了热休克蛋白72重组腺病毒,热休克蛋白72能够促进细胞凋亡,从转录水平上调p53蛋白的表达.结论 热休克蛋白72可能通过上调p53蛋白的表达促进细胞凋亡.     

Expression of HSP70 and JNK-related proteins in human liver cancer: Potential effects on clinical outcome

BACKGROUND: Activation of stress-activated protein kinase/c-Jun N-terminal kinase was inhibited in cells, in which heat shock protein70 was induced to a high level, indicating that heat shock protein70 might be anti-apoptosis protein. AIM: We examined the expression of heat shock protein70 and c-Jun N-terminal kinase signal transduction pathway in human liver carcinoma to explore their relationship and clinical parameters. PATIENTS AND METHODS: The expression of heat shock protein70, c-Jun N-terminal kinase1, c-Jun N-terminal kinase2 and c-Jun were detected immunohistochemically in 62 samples of liver cancer. Western blot was used to confirm immunostaining results. RESULTS: Heat shock protein70 expression showed a positive correlation with the malignant differentiation in liver carcinoma (r=0.449, P<0.0005). The expression of c-Jun N-terminal kinase1, c-Jun N-terminal kinase2, and c-Jun showed a negative correlation with the malignant differentiation in liver carcinoma (r=-0.351, P=0.005; r=-0.303, P=0.017; r=-0.302, P=0.017). Heat shock protein70 expression was correlated with c-Jun N-terminal kinase1 (r=-0.385, P=0.002), c-Jun N-terminal kinase2 (r=-0.309, P=0.015) and c-Jun (r=-0.302, P=0.017). Expression of heat shock protein70, as well as c-Jun N-terminal kinase1, was correlated with recurrence-free survival after the resection. Heat shock protein70 was associated with prognosis (P=0.004). CONCLUSION: Expression of heat shock protein70 and c-Jun N-terminal kinase-related proteins might be an indicator of malignant potential in liver carcinoma. The balance between heat shock protein70 and c-Jun N-terminal kinase-related protein may increase the stability of liver cancer cells in stress. Negative expression of heat shock protein70 might be a protective factor of recurrence of liver carcinoma.     

Heat shock induces expression of OSTC/DC2, a novel subunit of oligosaccharyltransferase,in vitro and in vivo

Mammalian oligosaccharyltransferase complex subunit OSTC/DC2 protein has recently been shown to be a new subunit of the oligosaccharyltransferase; however, its physiological role is still unclear. Here, we report the expression pattern of OSTC/DC2 protein in the context of heat shock stress. Its upregulation was detected both in cells treated with heat shock in vitro and in an animal model of heat shock in vivo. Northern blot analysis indicated that OSTC/DC2 mRNA is ubiquitously expressed in various human tissues, with abundant expression in the placenta and liver. The temporal changes of OSTC/DC2 protein expression following acute heat shock in human malignant glioblastoma cell line U87MG and mice were analyzed by Western blot assay. In general, expression of OSTC/DC2 protein was elevated after heat shock; however, the time courses of the change of OSTC/DC2 protein expression varied in different tissues. In the cerebellum, heat shock induction of OSTC/DC2 protein and activation of AKT, a key regulator of stress response, followed a similar time course. These results suggest that the upregulation of OSTC/DC2, a novel component of the oligosaccharyltransferase complex, is part of the mammalian heat shock response.     

阿奇霉素诱导的急性肝损伤小鼠肝组织HSP27表达的动态变化

目的研究热休克蛋白27(HSP27)在阿奇霉素诱导的小鼠急性肝损伤肝组织中的动态变化。方法以800mg.kg-1阿奇霉素腹腔注射建立小鼠急性肝损伤模型,设3h、6h、12h、24h、30h、36h、42h、48h和54h 9个观察时间点,每个时间点取10只小鼠,检测血清ALT和AST活性,采用免疫印迹法检测小鼠肝组织HSP27的表达变化。结果在注射阿奇霉素后,小鼠血清AST和ALT活性随着时间的延长逐渐升高,于24h达到高峰,自54h逐渐恢复到对照组水平;在注射阿奇霉素后3h肝脏HSP27表达开始升高,6h达到高峰,自12h开始下降,并于30h恢复至对照组水平。结论在阿奇霉素诱导的小鼠急性肝损伤过程中肝组织表达HSP27出现显著的动态变化,说明它可能参与了急性肝损伤的病理生理过程。     

The interaction and cellular localization of HSP27 and ERbeta are modulated by 17beta-estradiol and HSP27 phosphorylation

Recently, we identified heat shock protein 27 (HSP27) as an estrogen receptor-β (ERβ) associated protein that acts as a co-repressor of estrogen signaling and serves as a biomarker of atherosclerosis. In this study, we sought to further characterize the subcellular interaction of HSP27 and ERβ, as well as explore the factors that may modulate this interaction. In vitro we determined that phosphorylated HSP27 is retained in the cytoplasm after treatment with 17β-estradiol and to a lesser extent with heat shock. Under all experimental conditions ERβ was found to be slightly more abundant in the cytoplasm compared to the nucleus. HSP27 and ERβ associate in both the cytoplasm and nucleus, however, co-localization studies reveal that in the presence of 17β-estradiol, a significant portion of this interaction occurs outside of the nucleus. These data highlight an extranuclear interaction between ERβ and HSP27 that may be of potential importance in modulating estrogen signaling.     

热休克蛋白70与血管性认知功能障碍

脑卒中后体内有一系列的神经生化方面的改变,热休克蛋白是其中之一。有研究显示热休克蛋白70的改变与认知功能障碍相关,现就其之间的研究进展作一综述,为血管性认知功能障碍的更深一步研究、早期预防和治疗血管性认知障碍提供理论依据。     

Immunogenic Hsp-70 Is Overexpressed in Colorectal Cancers With High-Degree Microsatellite Instability

PURPOSE Colorectal cancers that display high-degree mi-crosatellite instability are associated with an improved prognosis and evidence of an activated host immune response. Molecular analyses have suggested that heat shock proteins, a family of proteins that have key immunologic functions, are upregulated in these cancers. We aimed to explore the expression of heat shock proteins 70 and 110 and their relationship to microsatellite instability, survival, and other clinicopathologic parameters. METHODS Twenty-six colorectal cancers that displayed microsatellite instability were matched by age, stage, and site in the colorectum to 26 microsatellite-stable cancers. Immunohistochemistry was used to detect expression of both markers. RESULTS The microsatellite-unstable group showed significantly higher expression of heat shock protein 70 than the microsatellite-stable group (P = 0.006), and patients undergoing curative resections for unstable cancers had improved prognosis compared with their stable counterparts (P = 0.026). Significantly, in a multivariate survival analysis, low or absent heat shock protein 70 expression was independently associated with a poor outcome (P = 0.001). CONCLUSIONS Heat shock protein 70 has known functions that promote antitumor immune responses. Its overexpression in colorectal cancers with microsatellite instability may be pivotal to explaining these tumors’ enhanced immunogenicity and improved prognosis. Supported by the Bowel & Cancer Research, Registered U.K. Charity No. 328667.     

Heat Shock Preconditioning Induces Protein Carbonylation and Alters Antioxidant Protection in Superficially Injured Guinea Pig Gastric Mucosa In Vitro

According to our previous studies, heat shock preconditioning of gastric mucosa requires modulation of protein synthesis and eicosanoid pathways to induce protection against superficial injury. This may be caused by heat shock–induced oxidative stress. We studied the effect of heat shock preconditioning with normothermic recovery on redox status in superficially injured (1.25 mmol NaCl for 5 min) Ussing chamber perfused guinea pig gastric mucosa allowed to recover for 3 hr after injury. Protein oxidation, lipid peroxidation, level of superoxide dismutase, level of heat shock protein 72 (HSP72), and level of oxygen radical absorbance capacity were measured. Superficial injury increased lipid peroxidation. Heat shock preconditioning decreased oxygen radical absorbance capacity and increased protein carbonyl and HSP72 levels, but inhibited electrophysiologic recovery. Exposure to indomethacin and arachidonic acid (AA) partially abolished this pro-oxidative and inhibitory effect on recovery, but maintained HSP72 levels and decreased protein carbonyls, lipid peroxidation, and oxygen radical absorbance capacity. In conclusion, superficial injury increased lipid peroxidation. Heat shock preconditioning alone induced oxidative stress via indomethacin- and AA-sensitive mechanisms. The development of optimal cytoprotective strategy may therefore require control of oxidative stress and modulation of the eicosanoid pathways.     

热休克蛋白与2型糖尿病发生发展的关系

热休克蛋白是一种进化上高度保守的细胞应激蛋白,参与调节多种蛋白质的生物活性。2型糖尿病是由遗传、环境、行为多种危险因素共同参与和相互作用引起的多因子病,发病机制主要涉及到胰岛素抵抗和胰岛素分泌缺陷。本文就热休克蛋白与2型糖尿病发生发展之间的关系进行综述。