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1.
    
Heat shock proteins (HSPs) are a family of cellular proteins involved in a variety of biological functions including chaperone activity. HSPs are classified based on their molecular weight and each family has several isoforms in eukaryotes. HSP40 is the most diverse family acting as a co-chaperone for the highly conserved HSP70 family. Some of the isoforms are reported to be induced during heat stress. Few studies have also highlighted the diverse role of some isoforms in different stress conditions including viral infections. But till date, no study has comprehensively examined the expression profile of different HSP40 and 70 isoforms in either heat stress or HIV-1 infection, a virus that is responsible for the pandemic of AIDS. In the present study, we have compared the mRNA expression profile of HSP40 and HSP70 isoforms during heat stress and HIV-1 infection in a T-cell line and also validated the HIV-1 stress results in peripheral blood mononuclear cells. In case of HSP70, we observed that three isoforms (HSPA1A, HSPA1B, and HSPA6) are highly upregulated during heat stress, but these isoforms were found to be downregulated during the peak of HIV-1 infection. While in case of HSP40, we found that only DNAJA4, DNAJB1, and DNAJB4 showed significant upregulation during heat stress, whereas in HIV-1 infection, majority of the isoforms were induced significantly. Stress-dependent differential expression observed here indicates that different HSP40 and HSP70 isoforms may have specific roles during HIV-1 infection and thus could be important for future studies.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-020-01185-y.  相似文献   

2.
摘要 目的:探讨血清缺氧诱导因子-1α(HIF-1α)、热休克蛋白(HSP)27、HSP70、HSP90α与肝细胞癌(HCC)患者经肝动脉化疗栓塞术(TACE)治疗疗效的关系。方法:选取2021年6月~2023年6月在南充市中心医院接受TACE治疗的HCC患者125例,根据TACE治疗疗效分为无效组(47例)和有效组(78例)。采用酶联免疫吸附法检测血清HIF-1α、HSP27、HSP70、HSP90α。多因素Logistic回归分析影响HCC患者TACE治疗疗效的因素,受试者工作特征(ROC)曲线分析血清HIF-1α、HSP27、HSP70、HSP90α对HCC患者TACE治疗无效的预测价值。结果:与有效组比较,无效组血清HIF-1α、HSP27、HSP70、HSP90α水平升高(P<0.05)。多因素Logistic回归分析显示,低分化、血管侵犯和HIF-1α、HSP27、HSP70、HSP90α升高为HCC患者TACE治疗无效的独立危险因素(P<0.05)。血清HIF-1α、HSP27、HSP70、HSP90α联合预测HCC患者TACE治疗无效的曲线下面积为0.958,大于血清HIF-1α、HSP27、HSP70、HSP90α单独预测的0.750、0.739、0.742、0.749。结论:血清HIF-1α、HSP27、HSP70、HSP90α升高是HCC患者TACE治疗无效的独立危险因素,血清HIF-1α、HSP27、HSP70、HSP90α联合预测HCC患者TACE治疗无效的价值较高。  相似文献   

3.
    
Heat shock proteins (HSP) are critical elements for the preservation of cellular homeostasis by participating in an array of biological processes. In addition, HSP play an important role in cellular protection from various environmental stresses. HSP are part of a large family of different molecular mass polypeptides, displaying various expression patterns, subcellular localizations, and diversity functions. An unexpected observation was the detection of HSP on the cell surface. Subsequent studies have demonstrated that HSP have the ability to interact and penetrate lipid bilayers by a process initiated by the recognition of phospholipid heads, followed by conformational changes, membrane insertion, and oligomerization. In the present study, we described the interaction of HSPA8 (HSC70), the constitutive cytosolic member of the HSP70 family, with lipid membranes. HSPA8 showed high selectivity for negatively charged phospholipids, such as phosphatidylserine and cardiolipin, and low affinity for phosphatidylcholine. Membrane insertion was mediated by a spontaneous process driven by increases in entropy and diminished by the presence of ADP or ATP. Finally, HSPA8 was capable of driving into the lipid bilayer HSP90 that does not display any lipid biding capacity by itself. This observation suggests that HSPA8 may act as a membrane chaperone.  相似文献   

4.
    
Abstract: The heat-shock protein 90 (HSP90) from tobacco VBIO cells specifically binds to nitrocellulose that had been coated with polymerized microtubules or tubulin dimers. HSP90 is expressed preferentially during cell division and becomes down-regulated during cell elongation. HSP90 cofractionates with tubulin dimers during affinity chromatography with sepharose coupled to the tubulin-binding drug ethyl N-phenylcarbamate (EPC). Binding of HSP90 to EPC-sepharose depends on the presence of tubulin. Antibodies against tubulin and HSP90 immunoadsorb HSP90 and tubulin, respectively. These results demonstrate that HSP90 behaves as a microtubule-binding protein in vitro.  相似文献   

5.
This study extends to the protein level our previous observations, which had established the stage and cellular specificity of expression of hsp86 and hsp84 in the murine testis in the absence of exogenous stress. Immunoblot analysis was used to demonstrate that HSP86 protein was present throughout testicular development and that its levels increased with the appearance of differentiating germ cells. HSP86 was most abundant in the germ cell population and was present at significantly lower levels in the somatic cells. By contrast, the HSP84 protein was detected in the somatic cells of the testis rather than in germ cells. The steady-state levels of HSP86 and HSP84 paralleled the pattern of the expression of their respective mRNAs, suggesting that regulation at the level of translation was not a major mechanism controlling hsp90 gene expression in testicular cells. Immunoprecipitation analysis revealed that a 70-kDa protein coprecipitated with the HSP86/HSP84 proteins in testicular homogenates. This protein was identified as an HSP70 family member by immunoblot analysis, suggesting that HSP70 and HSP90 family members interact in testicular cells. © 1993Wiley-Liss, Inc.  相似文献   

6.
Inhibitors of the heat shock response: biology and pharmacology   总被引:2,自引:0,他引:2  
Powers MV  Workman P 《FEBS letters》2007,581(19):3758-3769
A number of human diseases can be linked to aberrations in protein folding which cause an imbalance in protein homeostasis. Molecular chaperones, including heat shock proteins, act to assist protein folding, stability and activity in the cell. Attention has begun to focus on modulating the expression and/or activity of this group of proteins for the treatment of a wide variety of human diseases. This review will describe the progress made to date in developing pharmacological modulators of the heat shock response, including both agents which affect the entire heat shock response and those that specifically target the HSP70 and HSP90 chaperone families.  相似文献   

7.
8.
    
Molecular chaperones assist de novo protein folding and facilitate the refolding of stress‐denatured proteins. The molecular chaperone concept was coined nearly 35 years ago, and since then, tremendous strides have been made in understanding how these factors support protein folding. Here, we focus on how various chaperone proteins were first identified to play roles in protein folding. Examples are used to illustrate traditional routes of chaperone discovery and point out their advantages and limitations. Recent advances, including the development of folding biosensors and promising methods for the stabilization of proteins in vivo, provide new routes for chaperone discovery.  相似文献   

9.
Pardosa pseudoannulata is the main predatory natural enemy of crop pests in a paddy ecosystem. When P. pseudoannulata is exposed to unfavorable temperature conditions, the response of heat shock proteins could resist the damage, and is therefore, conducive to the organism’s rapid adaptation to the surrounding stress environment. In this study, we explored the roles of hsp70 and hsp90 genes in response to heat stress, using the rapid amplification of cDNA ends technique and cloned full-length cDNAs of Pphsp70, Pphsp83, and Pphsp90. The mRNA expression levels of the three genes under different temperature stresses (25, 28, 31, 34, 37, 40, and 43 °C) and with different duration stresses (4, 8, 12, 16, and 20 h) were analyzed by quantitative real-time polymerase chain reaction. The full-length cDNA of Pphsp70, Pphsp83, and Pphsp90 was 2331 base pair (bp), 2466 bp, and 2663 bp, respectively. Phylogenetic analysis of amino acid sequences of Pphsp70, Pphsp83, and Pphsp90 showed that the sequences had high homology with that of other spiders. The mRNA expression of all three genes was extremely significantly up-regulated at 43 °C. Moreover at 43 °C, the expression of all three genes in both female and male spiders at the duration of 4 h was the highest compared to that of other stress duration groups. Therefore, it can be inferred that the three genes of P. pseudoannulata play a crucial protective role in resistance in a high-temperature environment.  相似文献   

10.
The quasi-stationary distribution of the stochastic logistic model is studied in the parameter region where its body is approximately normal. Improved asymptotic approximations of its first three cumulants are derived. It is shown that the same results can be derived with the aid of the moment closure method. This indicates that the moment closure method leads to expressions for the cumulants that are asymptotic approximations of the cumulants of the quasi-stationary distribution.  相似文献   

11.
Quasi-stationarity and time to extinction are studied for the classic endemic model. Attention is restricted to the transition region in parameter space where the quasi-stationary distribution is non-normal. A new approximation of the marginal distribution of infected individuals in quasi-stationarity is presented. It leads to a simple explicit expression for an approximation of the critical community size in terms of model parameters.  相似文献   

12.
13.
    
In this study, we investigated whether exposure to 2450 MHz high-frequency electromagnetic fields (HFEMFs) could act as an environmental insult to evoke a stress response in A172 cells, using HSP70 and HSP27 as stress markers. The cells were exposed to a 2450 MHz HFEMF with a wide range of specific absorption rates (SARs: 5-200 W/kg) or sham conditions. Because exposure to 2450 MHz HFEMF at 50-200 W/kg SAR causes temperature increases in culture medium, appropriate heat control groups (38-44 degrees C) were also included. The expression of HSP 70 and HSP 27, as well as the level of phosphorylated HSP 27 ((78)Ser) (p-HSP27), was determined by Western blotting. Our results showed that the expression of HSP 70 increased in a time and dose-dependent manner at >50 W/kg SAR for 1-3 h. A similar effect was also observed in corresponding heat controls. There was no significant change in HSP 27 expression caused by HFEMF at 5-200 W/kg or by comparable heating for 1-3 h. However, HSP 27 phosphorylation increased transiently at 100 and 200 W/kg to a greater extent than at 40-44 degrees C. Phosphorylation of HSP 27 reached a maximum after 1 h exposure at 100 W/kg HFEMF. Our results suggest that exposure to a 2450 MHz HFEMF has little or no apparent effect on HSP70 and HSP27 expression, but it may induce a transient increase in HSP27 Phosphorylation in A172 cells at very high SAR (>100 W/kg).  相似文献   

14.
The steady-state levels of four members of the heat shock proteins families (HSP84, HSC73, HSP71, and HSP25) were examined by immunoblot analysis of several different tissues of young and adult mice in the absence of stress. These hsps were detected in all tissues but their level was variable. The levels of HSC73 and HSP84 varied only slightly between different tissues in either young or adult mice, with the exception of skin where these hsps were found in reduced amounts. In contrast, the stress-inducible member of the HSP70 family, HSP71, was found to be expressed in all tissues but in amounts which differed by as much as two orders of magnitude between tissues. In general, the levels of both HSP71 and HSP25 were found to be tissue dependent, with higher levels found in tissues such as stomach, intestine, colon and bladder, tissues which are exposed to toxic environmental or metabolic products, and which may concentrate these substances by water resorption and/or be exposed to them for longer periods. The levels of HSP71 and HSP25 were generally positively correlated both in young and adult mice although this correlation was not found in certain tissues such as kidney, testes, and bone. Tissues of young mice contained lower amounts of HSP25 and HSP71 than were found in the same tissues from adults. We conclude that hsps are expressed in all tissues of the mouse in the absence of stress and that some organs, particularly those exposed to potentially toxic metabolites, show a higher level of expression of HSP71 and HSP25. © 1993Wiley-Liss, Inc.  相似文献   

15.
目的:研究清胰利胆颗粒对重症急性胰腺炎患者血清高迁移率族蛋白1(HMGB1)、热休克蛋白70(HSP70)、热休克蛋白27(HSP27)、白介素-8(IL-8)水平的影响。方法:选取2015年8月至2016年7月我院收治的84例重症急性胰腺炎患者,根据随机数字法分为观察组和对照组,42例每组。对照组采取常规方案完成治疗,观察组在此基础上使用清胰利胆颗粒治疗。比较两组患者临床疗效,血淀粉酶恢复至正常时间、白细胞恢复至正常时间、胃肠功能恢复至正常时间、腹痛缓解时间及血清HMGB1、HSP70、HSP72、IL-8水平。结果:治疗后,观察组临床总有效率显著高于对照组[92.86%(39/42)比71.43%(30/42)](P0.05)。观察组的血淀粉酶恢复至正常时间、白细胞恢复至正常时间、胃肠功能恢复至正常时间及腹痛缓解时间显著短于对照组(P0.05)。治疗前,两组患者HMGB1、HSP70、HSP72、IL-8水平比较无显著差异(P0.05),治疗后,两组患者HMGB1、HSP70、HSP72、IL-8水平和治疗前相比显著下降(P0.05),和对照组相比,观察组的HMGB1、HSP70、HSP72、IL-8水平较低(P0.05)。结论:清胰利胆颗粒能有效降低重症急性胰腺炎患者血清HMGB1、HSP70、HSP27、IL-8水平,且可提高临床疗效。  相似文献   

16.
    

Introduction

Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60), recently renamed HSPD1, and bacterial HSP60 are highly homologous, immunological cross-reactivity has been proposed as a mechanism of disease initiation. However, previous investigations of the humoral immune response to HSP60 in SpA patients have lacked determination of immunoglobulin G (IgG) subclasses and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27.

Methods

IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60 of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls. The Mann-Whitney U test and Wilcoxon matched pairs test were used to compare the antibody levels in different and paired groups, respectively. P < 0.01 was considered significant. The Spearman nonparametric correlation was used to determine correlation between antibody levels and between antibody levels and the disease parameters.

Results

Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3 to human HSP60 tended to decrease over time. The antibody response to human HSP60 was predominantly of the IgG3 subclass, and patients with high levels of IgG3 to this antigen had low levels of IgG1, indicating an inverse association. Different IgG subclasses were produced against bacterial and human HSP60 in the same serum sample, IgG1 and IgG3, respectively, indicating that there was no cross-reaction.

Conclusions

A significant association was observed between axial SpA and the presence of IgG1/IgG3 antibodies to human HSP60 and of IgG1 to S. enterica Enteritidis and C. trachomatis. Generation of antibodies to human HSP60 was independent of the presence of antibodies to bacterial HSP60. No association was observed between clinical and MRI changes with antibodies over time. Altogether, such antibodies do not reflect the disease activity in these patients.This study has been approved by the Regional Research Ethics Committee of Central Jutland, Denmark. Trial registration numbers: 20050046 and 20100083  相似文献   

17.
    
Under conditions of extreme heat stress, the process of autophagy has previously been shown to protect human cells, but the exact body temperature at which autophagic activation occurs is largely unknown. Further, the interplay between autophagy, the heat shock response (HSR), inflammation, and apoptosis have yet to be examined together under temperature conditions representative of human internal body temperatures at rest (37 °C) or under severe heat stress conditions (41 °C). Thus, the purpose of this study was to examine threshold changes in autophagy, the HSR, inflammation, and apoptosis to increasing levels of ex vivo heat stress. Whole blood was collected from 20 young (23 ± 4 years; 10 men, 10 women) physically active participants. Peripheral blood mononuclear cells (PBMCs) were isolated immediately (baseline) and after 90-min of whole blood heating in 37, 39, and 41 °C water baths, representative of normal resting (non-heat stress) as well as moderate and severe heat stress conditions in humans, respectively. At 37 °C, increased autophagic activity was demonstrated, with no change in the HSR, and inflammation. Subsequently, responses of autophagy, the HSR, and inflammation increased with a moderate heat stress (39 °C), with further increases in only autophagy and the HSR under a severe heat stress of 41 °C. We observed no increase in apoptosis under any temperature condition. Our findings show that in human PBMCs, the autophagy and HSR systems may act cooperatively to suppress apoptotic signaling following heat stress, which may in part be mediated by an acute inflammatory response.  相似文献   

18.
不同热休克蛋白在肾细胞癌组织中的表达及其意义   总被引:5,自引:0,他引:5  
目的 研究HSPgp96、HSP90、HSP70在肾细胞癌组织中的表达及其相互关系。方法 应用免疫组化S P法检测 5 4例肾细胞癌组织标本中HSPgp96、HSP90、HSP70的表达情况。结果 在肾细胞癌组织中HSPgp96、HSP90、HSP70表达明显较正常肾组织增强 (P <0 0 5 ) ,阳性率分别为 88 9%、 85 2 %、 90 7% ,三者之间无明显差异性 (P >0 0 5 ) ,其表达程度均与肾细胞癌临床分期、病理分级及细胞类型无显著相关性 (P >0 0 5 )。结论 HSPgp96、HSP90、HSP70的高表达在肾细胞癌的发生、发展中起促进作用 ,尤其是在加强肿瘤抗原的呈递、表达上具有重要临床应用价值。  相似文献   

19.
  总被引:3,自引:0,他引:3  
The macrophage scavenger receptor (MSR) is a trimeric membrane protein which binds to modified low-density lipoprotein (LDL) and has been indicated in the development of atherosclerosis. It has recently been demonstrated that the N-terminal cytoplasmic domain of MSR has an important role in the efficient internalization and cell-surface expression of the receptor. This study shows that the N-terminal cytoplasmic domain in bovine was constructed using a peptide architecture technique in which the peptide chain was bundled at their C-terminus to yield a trimeric form and that this did not form an ordered structure. Furthermore, the binding proteins to the cytoplasmic domain of MSR were determined for the first time using a peptide affinity column. Sequence analyses of the specific binding proteins in bovine revealed that heat shock protein 90 (HSP90), heat shock protein 70 (HSP70), leucine aminopeptidase (LAP), adenocylhomocysteinase, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were included. GST-pull-down assay and immunoprecipitation analyses on HSP90, HSP70, and GAPDH showed that all these proteins could bind to the cytoplasmic domain of MSR in vitro and in vivo. These proteins interact with the cytoplasmic domain directly and may have an effect on the functions of MSR such as internalization, cell-surface expression, and signal transduction.  相似文献   

20.
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