Heat Shock Proteins Inducement in Wheat Seedling

High temperature is an important limiting factor to the improvement of wheat yield. When suffered hot stress,wheat will produce a series of heat shock proteins to adapt this adversity. In different upgrowth phases,or different heat-resistant crop varieties,the heat shock protein exist differences. Therefore,study on differences of heat shock protein has significant theoretical and practical meaning for researching heat resistance of wheat. By using SDS-PAGE method,the inducing conditions and manifestation of heat shock protein were studied,which provided theoretical basis for yield increasing of wheat.

Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules

AIM: Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)related HCC.METHODS: Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucoseregulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.RESULTS: Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r= 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.CONCLUSION: The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBVrelated hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.

Advance in Research on Biological Function and TranscriptionalControl of Heat Shock Proteins

The regulation of heat shock transcription factor to heat shock protein expression and the newest knowledge about the effect of heat shock protein on aging,immune response and the balance of cell survival and apoptosis are summarized in the paper.

Potential involvement of heat shock proteins in pancreaticduodenal homeobox-1-mediated effects on the genesis of gastric cancer: A 2D gel-based proteomic study

AIM To identify functional proteins involved in pancreaticduodenal homeobox-1(PDX1)-mediated effects on gastric carcinogenesis.METHODS A PDX1-overexpressed model was established by transfecting gastric cancer cell line SGC7901 with pcDNA3.1(+)-PDX1 vector(SGC-PDX1). Transfection with empty pcDNA3.1 vector(SGC-pcDNA) served as control. Comparative protein profiles of the two groups were analyzed by two-dimensional electrophoresis basedproteomics(2 DE gel-based proteomics). The differential proteins identified by 2 DE were further validated by qRTPCR and immunoblotting. Finally, co-immunoprecipitation was used to determine any direct interactions between PDX1 and the differential proteins.RESULTS2 DE gel proteomics identified seven differential proteins in SGC-PDX1 when compared with those in SGC-pcDNA. These included four heat shock proteins(HSPs; HSP70 p1 B, HSP70 p8, HSP60, HSP27) and three other proteins(ER60, laminin receptor 1, similar to epsilon isoform of 14-3-3 protein). Immunoblotting validated the expression of the HSPs(HSP70, HSP60, HSP27). Furthermore, their expressions were lowered to 80%, 20% and 24%, respectively, in SGC-PDX1, while PDX1 exhibited a 9-fold increase, compared to SGC-pcDNA. However, qRT-PCR analysis revealed that mRNA levels of the HSP s were increased in SGC-PDX1, suggesting that the expression of the HSP s was post-translationally regulated by the PDX1 protein. Finally, co-immunoprecipitation failed to identify any direct interaction between PDX1 and HSP70 proteins.CONCLUSION This study demonstrates the potential involvement of HSPs in PDX1-mediated effects on the genesis of gastric cancer.

Expression profiles of two small heat shock proteins and antioxidant enzyme activity in Mytilus galloprovincialis exposed to cadmium at environmentally relevant concentrations

Small heat shock proteins encompass a widespread but diverse class of proteins, which play key roles in protecting organisms from various stressors. In the present study, the full-length cDNAs of two small heat shock proteins （MgsHSP22 and MgsHSP24.1） were cloned from Mytilus galloprovincialis, which encoded peptides of 181 and 247 amino acids, respectively. Both MgsHSP22 and MgsHSP24.1 were detected in all tissues examined by real-time PCR, with the highest expression being observed in muscle and gonad tissues. The real-time PCR results revealed that Cd significantly inhibited MgsHSP22 expression at 24 h and MgsHSP24.1 at 24 and 48 h under 5 ug/L Cd2＋ exposure. MgsHSP24.1 expression was also significantly inhibited after 50 ug/L Cd2＋ exposure for 48 h. With regard to antioxidant enzymes, increased GPx and CAT activity were detected under Cd2＋ stress （5 and 50 ug/L）, while no significant difference in SOD activity was observed throughout the experiment. Overall, both MgsHsps and antioxidant enzymes revealed their potential as Cd stress biomarkers in M. galloprovincialis.

Polaprezinc protects human colon cells from oxidative injury induced by hydrogen peroxide:Relevant to cytoprotective heat shock proteins

AIM： To investigate the effect of polaprezinc on cellular damage induced by hydrogen peroxide （H202） in human colon CaCo2 cells. METHODS： CaCo2 cells were treated with polaprezinc （10-100 pmol/L） for 6 h. After polaprezinc treatment, the cells were incubated with H202 （20μmol/L） for 1 h. Cell viability was measured by MTT assay. Western blot analysis for heat shock protein （HSP） 27 and HSP72 in the cells was performed. Moreover, cells were pretreated with quercetin （200 μmol/L）, an inhibitor of HSP synthesis, 2 h before polaprezinc treatment, and cell viability and the expression of HSP27 and 72 were assessed in these cells. RESULTS： Polaprezinc significantly protected CaCo2 cells from cell damage induced by H2O2, and up-regulated the expressions of HSP27 and HSP72 in the cells （10, 30 and 100 pmol/L of polaprezinc; 35.0% ± 7.7%, 58.3% ± 14.6% and 64.2% ± 8.2%, respectively. P 〈 0.01 versus polaprezinc-nontreated cells; 6.0% ± 4.4%）. Quercetin inhibited the up-regulation of HSP27 and HSP72 by polaprezinc and diminished the protective effect of polaprezinc against H2O2-caused injury in the cells. CONCLUSION： Polaprezinc is a useful therapeutic agent for treatment of colitis and its effects depend on the function of cytoprotective HSP in colon.

Involvement of heat shock proteins in gluten-sensitive enteropathy

Gluten-sensitive enteropathy,also known as coeliac disease(CD),is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients.As it is triggered by dietary gluten and related prolamins present in wheat,rye and barley,the accepted treatment for CD is a strict gluten-free diet.However,a complete exclusion of gluten-containing cereals from the diet is often difficult,and new therapeutic strategies are urgently needed.A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins(HSPs),which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors.HSPs are expressed in several tissues,including the gastrointestinal tract,and their levels are significantly increased under stress circumstances.HSPs exert immunomodulatory effects,and also play a crucial role in the maintenance of epithelial cell structure and function,as they are responsible for adequate protein folding,influence the degradation of proteins and cell repair processes after damage,and modulate cell signalling,cell proliferation and apoptosis.The present review discusses the involvement of HSPs in the pathophysiology of CD.Furthermore,HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective,immunomodulatory,and anti-apoptotic effects in the intestinal mucosal barrier.

Prognostic and immunological roles of heat shock protein A4 in lung adenocarcinoma

BACKGROUND Heat shock protein A4(HSPA4)belongs to molecular chaperone protein family which plays important roles within variable cellular activities,including cancer initiation and progression.However,the prognostic and immunological significance of HSPA4 in lung adenocarcinoma(LUAD)has not been revealed yet.AIM To explore the prognostic and immunological roles of HSPA4 to identify a novel prognostic biomarker and therapeutic target for LUAD.METHODS We assessed the prognostic and immunological significance of HSPA4 in LUAD using data from The Cancer Genome Atlas database.The association between HSPA4 expression and clinical-pathological features was assessed through Kruskal-Wallis and Wilcoxon signed-rank test.Univariate/multivariate Cox regression analyses and Kaplan-Meier curves were employed to evaluate prognostic factors,including HSPA4,in LUAD.Gene set enrichment analysis(GSEA)was conducted to identify the key signaling pathways associated with HSPA4.The correlation between HSPA4 expression and cancer immune infiltration was evaluated using single-sample gene set enrichment analysis(ssGSEA).RESULTS Overexpressing HSPA4 was significantly related to advanced pathologic TNM stage,advanced pathologic stage,progression disease status of primary therapy outcome and female subgroups with LUAD.In addition,increased HSPA4 expression was found to be related to worse disease-specific survival and overall survival.GSEA analysis indicated a significant correlation between HSPA4 and cell cycle regulation and immune response,particularly through diminishing the function of cytotoxicity cells and CD8 T cells.The ssGSEA algorithm showed a positive correlation between HSPA4 expression and infiltrating levels of Th2 cells,while a negative correlation was observed with cytotoxic cell infiltration levels.CONCLUSION Our findings indicate HSPA4 is related to prognosis and immune cell infiltrates and may act as a novel prognostic biomarker and therapeutic target for LUAD.

The Role of Heat Shock Proteins in Mammary Neoplasms: A Brief Review

Research into heat shock proteins (HSPs) for the clinical management of tumours has intensified as new evidence shows they can be used as biomarkers in carcinogenesis and are related to poor prognosis in some cancer types. Members of small HSP, HSP70 and HSP90 families have been studied extensively in breast cancer. This article reviews current understanding of the role of HSP and HSF-1 (Heat shock factor 1) expression in human breast cancer and looks at its potential diagnostic, prognostic and therapeutic value. The exciting progress that has been made using HSP 90 inhibitors in breast cancer treatment is examined and the results of preliminary studies on the expression of stress proteins in the animal model canine mammary tumours are also presented.

Heat shock and other apoptosis-related proteins as therapeutic targets in prostate cancer

Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.

Effect of Jianpiyiqi Prescription on the Expression of Heat Shock Proteins in Acetic Acid-induced Chronic Gastric Ulcer Rats

To investigate the effect of Jianpiyiqi prescription on the expression of heat shock proteins and the changes of HSPs in gastric ulcerated rats, the rat model of chronic gastric ulcer was induced by acetic acid. The SABC immunohistochemical method was used to observe HSP70 of mucosa around the gastric ulcer. Imaging analysis was performed. Western dot blot was used to detect HSPs contents in the plasma and gastric mucosal homogenate in each group. The results showed that HSP70 contents of the mucosa around the gastric ulcer in the model group and ranitidine treated group were increased as compared with control group . Jianpiyiqi could increase the expression of HSP70 of the mucosa around the gastric ulcer further as compared with that in the model group and ranitidine treated group . The HSP70 contents in the serum and mucosa in the model group and ranitidine treated group were increased as compared with control group ( P <0.01, P <0 05 respectively). HSP70 of serum and mucosa in the Jianpiyiqi treated group was higher than in the model group and ranitidine treated group ( P <0.05, P <0.01 respectively).It was concluded that HSP might play a role in the process of pathophysiology of gastric ulcer. Jianpiyiqi could enhance gastric ulcer healing through the protective mechanism of HSPs.

Expressions and clinicopathologic significance of five heat shock proteins in esophageal squamous cell carcinoma

Objective： To investigate the expressions of heat shock protein （hsp） 10, hsp27, hsp60, hsp70 and hsp90a in esophageal squarnous cell carcinoma （ESCC） and normal tissues along the incisal margin （TIM）, and discuss the clinicopathologic features about their expressions. Methods： 120 specimens from ESCC and 36 specimens from TIM were made into tissue chips. The presence and the levels of expression of hspl0, hsp27, hsp60, hsp70 and hsp90a were observed on tissue chips by immunohistochemistry EnVision^TM. Their correlations to clinicopathologic features were analyzed. Results： The positive staining rates of hsp10, hsp27, hsp60, hsp70 and hsp90a in ESCC and TIM were 53.8% and 37.5%, 62.0% and 42.1%, 92.7% and 63.2%, 57.9% and 22.2%, 33.7% and 18.5% respectively. There were no statistical significances between the differential expressions of hsp10, hsp27 and hsp90a in ESCC and TIM （P 〉 0.05）, but there were great statistical significances about hsp60 and hsp70 （P 〈 0.01）. The level of hsp27 declined with the lower grade of differentiation of ESCC （P 〈 0.05）. Except for hsp27, the positive expressions of the other four HSPs had no correlation to the clinicopathologic features of ESCC. Conclusion： The expressions of hsp10, hsp27, hsp60, hsp70 and hsp90a in ESCC and TIM were a common event. The levels of hsp60 and hsp70 in ESCC were higher than those in TIM. The level of hsp27 declined with the lower grade of differentiation of ESCC showed that it may be play a role in the differentiation of ESCC.

A Review of Heat Shock Proteins Research on Bemisia tabaci

Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) is the most destructive invasive pests in agricultural production and has a high tolerance to heat. Heat shock proteins play an essential role in life activities such as growth and development, reproduction and diapause of B. tabaci. At the same time, they are also crucial in resisting adverse environments and in adaptive evolution. The expression of heat shock protein in B. tabaci is not only related to temperature, but also to the tolerance of the environment. After receiving external stimuli, the expression level can be increased or decreased to maintain the stability of cells in vivo. This paper reviews the classification, biological characteristics, biological functions, and research status of HSPs in recent years. This mini-review will provide helpful information related to the use of heat shock proteins to study the occurrence and damage of B. tabaci. This has important theoretical and practical significance for revealing Hsps in explaining the population expansion mechanism of B. tabaci invasion and predicting population dynamics.

Insect heat shock proteins and their underlying functions

Considering huge number of insect species in the world,studies of heat shock proteins on insects are still very limited.Special focus of＂Insect heat shock proteins and their underlying functions＂provides a comprehensive knowledge for the given topics,which focuses on the heat shock proteins from four insect species：i）Five heat shock proteins（HSPs）from Cotesia chilonis were identified,and their expressional patterns under different temperatures were examined.

Heat shock proteins and immunotherapy

Being one of the most abundant intracellular proteins, heat shock proteins (HSPs) have many housekeeping functions which are crucial for the survival of organisms. In addition, some HSPs are new immunoactive molecules which play important roles in both adaptive and innate immunity. They could activate CD8 + and CD4 + lymphocytes, induce innate immune response including natural killer (NK) cell activation and cytokine secretion, and induce maturation of dendritic cells (DCs). These characteristics have been used for immunotherapy of various types of cancers and infectious diseases. This review focuses on the main HSP families——HSP70 and 90 families. The mechanism of HSPs′ function in eliciting immune response are elucidated and various forms of HSPs used in immunotherapy are discussed in details. At the end of this review, authors summarize clinical trials related to HSPs and evaluate their clinical efficacy.

Molecular Cloning the Gene of Small Heat Shock Protein in the Mitochondria and Endoplasmic Reticulum of Tomato

A cDNA Library was constructed with the heat shocked tomato ( Lycopersicon esculentum Mill.) flowers and then was screened with the probes of mitochondrial and endoplasmic reticulum conservative regions that were cloned by using RT-PCR. The complete cDNAs of mitochondrial and endoplasmic reticulum small heat shock protein ( shsp) were selected out from the cDNA library. Furthermore, the temperature responses of these shsp genes were determined. Northern hybridization showed that the heat response temperatures of both genes in tomato flower were lower than that in leaf and that mitochondria shsp in leaf was cold-inducible. In this paper, the molecular features of the cloned genes, the causes of the uncommon heat response temperatures of sHSP in newer and the cold inducible character of mitochondria shsp gene in leaf were discussed.

Abrogation of heat-shock protein (HSP)70 expression induced cell growth inhibition and apoptosis in human androgen-independent prostate cancer cell line PC-3m

Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.

Correlation between clinicopathology and expression of heat shock protein 70 and glucose-regulated protein 94 in human colonic adenocarcinoma

AIM: To investigate the correlation between clinicopathology and expression of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human colonic carcinoma. METHODS: The expression of HSP70 and grp94 was studied in 80 human colonic cancers with or without metastasis as well as in their adjacent mucous membrane by way of immunohistochemistry and pathology photograph analysis. RESULTS: The expression of HSP70 and grp94 was significantly higher in cancer than that in adjacent mucous membrane (92.5%, 85.0% vs 56.3%, 42.5%, P<0.01). HSP70 and grp94 expressed higher in moderately- and poorly-differentiated colonic cancers than that in their adjacent tissues (93.7%, 87.5%; 100%, 90% vs56.3%, 42.5%;P<0.01). Dukes C and D stages of colonic cancers showed higher positive rates than Dukes A and B stage groups (97.1%, 91.2%; 100%, 90.9%; vs 80%, 70%; 78.6%, 71.4%; P<0.05). There were definite differences in HSP70 and grp94 expression between metastasis groups and non-metastasis groups (100% vs 75%, 100% CONCLUSION: The HSP70 and grp94 expression rates in colonic cancer groups are significantly higher than that in their adjacent mucous membrane. The HSP70 and grp94 expression in poorly-differentiated colonic cancers with metastasis is significantly higher than well-differentiated cancers without metastasis. The overexpression of HSP70 and grp94 can be used as diagnostic or prognostic markers for colonic cancer.

What we know about ST13, a co-factor of heat shock protein, or a tumor suppressor?

This article is to summarize the molecular and functional analysis of the gene “suppression of tumorigenicity 13” (ST13). ST13 is in fact the gene encoding Hsp70 interacting protein (Hip), a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). By collaborating with other positive co-factors such as Hsp40 and the Hsp70-Hsp90 organizing protein (Hop), or competing with negative co-factors such as Bcl2-associated athanogen 1 (Bag1), Hip facilitates may facilitate the chaperone function of Hsc/Hsp70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and regulators of proliferation or apoptosis. Although the nomenclature of ST13 implies a role in the suppression of tumorigenicity (ST), to date available experimental data are not sufficient to support its role in cancer development, except for the possible down-regulation of ST13 in gastric and colorectal cancers. Further investigation of this gene at the physiological level would benefit our understanding of diseases such as endocrinological disorders, cancer, and neurodegeneration commonly associated with protein misfolding.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease

AIM: To determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) anti- body response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti- heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infec- tion was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA- positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Sys-temic levels of IgG to Hsp60 were increased in H pylori- negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti- Hsp60 antibodies may constitute a marker and/or a con- comitant pathogenic factor of the disease.