Function Of Heat Shock Proteins Research Articles

Cloning, expression analysis and In silico characterization of HSP101: a potential player conferring heat stress in Aegilops speltoides (Tausch) Gren.

The online version contains supplementary material available at 10.1007/s12298-021-01005-2.

The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.

Cells respond to protein-damaging (proteotoxic) stress by activation of the Heat Shock Response (HSR). The HSR provides cells with an enhanced ability to endure proteotoxic insults and plays a crucial role in determining subsequent cell death or survival. The HSR is, therefore, a critical factor that influences the toxicity of protein stress. While named for its vital role in the cellular response to heat stress, various components of the HSR system and the molecular chaperone network execute essential physiological functions as well as responses to other diverse toxic insults. The effector molecules of the HSR, the Heat Shock Factors (HSFs) and Heat Shock Proteins (HSPs), are also important regulatory targets in the progression of neurodegenerative diseases and cancers. Modulation of the HSR and/or its extended network have, therefore, become attractive treatment strategies for these diseases. Development of effective therapies will, however, require a detailed understanding of the HSR, important features of which continue to be uncovered and are yet to be completely understood. We review recently described and hallmark mechanistic principles of the HSR, the regulation and functions of HSPs, and contexts in which the HSR is activated and influences cell fate in response to various toxic conditions.

Identification of six heat shock protein 70 genes in Lasioderma serricorne (Coleoptera: Anobiidae) and their responses to temperature stress

Heat shock proteins (HSPs) play essential roles in stress tolerance in insects, such as the cigarette beetle, Lasioderma serricorne, which is an important pest of stored products. However, the function of HSPs in environmental stress response in L. serricorne is poorly understood. In this study, six cDNAs encoding putative HSP70s were identified in L. serricorne (LsHSP70-1 to LsHSP70-6). The LsHSP70 proteins identified have signature motifs of insect HSP70s and exhibit high amino-acid identity with their respective orthologs from other insect species. Phylogenetic analysis showed that these LsHSP70s fall into three major clans: HSP70 in the cytosol (four genes), endoplasmic reticulum (one gene), and mitochondria (one gene). LsHSP70 genes are differentially expressed in different developmental stages. LsHSP70-4 and LsHSP70-5 are mainly expressed at the larval stage, while LsHSP70-3 shows the highest level at the pupal stage. The other genes are ubiquitously expressed. Furthermore, the expression levels of LsHSP70-1 and LsHSP70-4 are significantly upregulated upon exposure to temperatures of both 0 and 15 °C, while LsHSP70-3 is inducible at 15 °C and LsHSP70-6 at 0 °C. In addition, treatment at 0 °C causes significant downregulation of LsHSP70-2 and LsHSP70-3. Exposure to a temperature of 30 °C upregulates LsHSP70-1 expression, while 35 and 40 °C treatments result in significantly enhanced transcription of all the LsHSP70 genes. To the best of the authors’ knowledge, this is the first report on the sequence characteristics, phylogenetic relationships, and expression profiles of HSP70 genes in L. serricorne. The cold- and heat-inducible regulation of LsHSP70s suggests that these genes are related to tolerance of abnormal temperatures.

Chaperone Networks in Fungal Pathogens of Humans.

The heat shock proteins (HSPs) function as chaperones to facilitate proper folding and modification of proteins and are of particular importance when organisms are subjected to unfavourable conditions. The human fungal pathogens are subjected to such conditions within the context of infection as they are exposed to human body temperature as well as the host immune response. Herein, the roles of the major classes of HSPs are briefly reviewed and their known contributions in human fungal pathogens are described with a focus on Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. The Hsp90s and Hsp70s in human fungal pathogens broadly contribute to thermotolerance, morphological changes required for virulence, and tolerance to antifungal drugs. There are also examples of J domain co-chaperones and small HSPs influencing the elaboration of virulence factors in human fungal pathogens. However, there are diverse members in these groups of chaperones and there is still much to be uncovered about their contributions to pathogenesis. These HSPs do not act in isolation, but rather they form a network with one another. Interactions between chaperones define their specific roles and enhance their protein folding capabilities. Recent efforts to characterize these HSP networks in human fungal pathogens have revealed that there are unique interactions relevant to these pathogens, particularly under stress conditions. The chaperone networks in the fungal pathogens are also emerging as key coordinators of pathogenesis and antifungal drug tolerance, suggesting that their disruption is a promising strategy for the development of antifungal therapy.

Cellular Functions of Small Heat Shock Proteins (HSPB) in Hepatocellular Carcinoma.

Heat shock proteins (HSPs) play an essential role as molecular chaperones in proteostasis. Small HSPs are a group of low-molecular-weight HSPs in the range of 12- 43 kDa and are classified as HSPB. Within the ten members of the family, HSPB1(HSP27), HSPB5 (αB-crystallin), HSPB6 (HSP20), and HSPB8 (HSP22) ubiquitously exist in various tissues, including liver tissue. These small HSPs undergo phosphorylation as a post-translational modification, and their functions are modulated. Hepatocellular carcinoma (HCC) is one of the most frequent cancers and the fourth leading cause of cancer-related death worldwide. HSPs play a cytoprotective role as molecular chaperones. Thus, HSPB has been generally considered to protect HCC cells and help the progression of HCC. On the other hand, recent studies from our laboratories have demonstrated suppressive roles of phospho-HSPB1, HSPB6, and HSPB8 in the progression of HCC. These findings may provide a basis for a novel defense system by HSPB against HCC progression. This review focuses on the cellular functions of HSPB in HCC and summarizes the current research.

Ac-HSP20 Is Associated With the Infectivity and Encystation of Acanthamoeba castellanii.

Acanthamoeba castellanii is a pathogenic and opportunistic free-living amoeba that causes Acanthamoeba keratitis (AK) and granulomatous amebic encephalitis (GAE) in immunocompromised individuals. The biological and pathogenic characterizations behind this opportunistic protozoan is not fully understood. This study aimed to determine the biological functions of heat shock protein (HSP)-20 of A. castellanii (Ac-HSP20) involved in the maintenance of life cycle and the infectivity of A. castellanii. Immunoscreening A. castellanii cDNA library with A. castellanii infected rabbit sera identified three positive clones, one of them was a putative heat shock protein (Ac-HSP20). The recombinant 23 kDa Ac-HSP20 protein (rAc-HSP20) was successfully expressed in Escherichia coli BL21 (DE3) and purified using metal affinity chromatography. The rabbits immunized with rAc-HSP20 produced high titer antibody (1:25,600). Immunolocalization with the antibody identified the expression of native Ac-HSP20 on the surface of both A. castellanii trophozoites and cysts. Further, Western blot with antibody identified that the expression of native Ac-HSP20 was 7.5 times higher in cysts than in trophozoites. Blocking Ac-HSP20 on the membrane of trophozoites with specific antibody or silencing Ac-hsp20 gene transcription by siRNA inhibited their transformation into cysts at the early stage but returned to normal at the late stage by stimulating the transcription of Ac-hsp20. Incubation of trophozoites with anti-Ac-HSP20 IgG increased macrophage-involved phagocytosis to the protozoa and inhibited trophozoite infectivity on the cornea of rabbits compared with that without antibody. Our study provides that Ac-HSP20 is a surface antigen involved in the encystation and infectivity of A. castellanii and thus an important target for vaccine and drug development.

Abundances of vitellogenin and heat shock protein 90 during ovarian and embryonic development of Exopalaemon carinicauda

To evaluate functions of vitellogenin (Vg) and heat shock protein 90 (Hsp90) during ovarian and embryonic development of Exopalaemon carinicauda, the cDNA of Vg (Ec-Vg) was cloned, and the abundances of Ec-Vg and heat shock protein 90 (Hsp90) (Ec-Hsp90) were determined during ovarian and embryonic development. During ovarian development, the concentration of Vg protein in hemolymph was markedly greater than in the ovary and hepatopancreas, and was greatest at sexual maturity. The relative abundance of Ec-Vg mRNA transcript was greatest in the hepatopancreas and almost undetectable in hemocytes. By combining mRNA transcript relative abundances with morphological results, a model was developed to explain the mRNA transcript relative abundance of Ec-Hsp90 and Ec-Vg during ovarian and embryonic development. The relative abundance of Ec-Vg mRNA transcript was greatest during the recovery period after reproduction had occurred (Stage V) and mature stage (Stage IV) in the ovary or hepatopancreas, respectively. There were marked associations of the patterns of Ec-Hsp90 and Ec-Vg mRNA transcript abundances both in hepatopancreas and ovary. During embryonic development, the relative abundance of the two mRNA transcripts were greatest at the metazoea and protozoea stages, respectively. These results indicate that Ec-Vg is produced primarily in the hepatopancreas, secreted into the hemolymph and transported into growing oocytes. It, therefore, is believed that Ec-Vg has an important function in the overall ovarian development and late embryonic development of E. carinicauda. In contrast, Ec-Hsp90 is a regulatory factor for Vg transcription and is important during early organogenesis in E. carinicauda.

Identifying Heat Shock Protein Families from Imbalanced Data by Using Combined Features.

Heat shock proteins (HSPs) are ubiquitous in living organisms. HSPs are an essential component for cell growth and survival; the main function of HSPs is controlling the folding and unfolding process of proteins. According to molecular function and mass, HSPs are categorized into six different families: HSP20 (small HSPS), HSP40 (J-proteins), HSP60, HSP70, HSP90, and HSP100. In this paper, improved methods for HSP prediction are proposed—the split amino acid composition (SAAC), the dipeptide composition (DC), the conjoint triad feature (CTF), and the pseudoaverage chemical shift (PseACS) were selected to predict the HSPs with a support vector machine (SVM). In order to overcome the imbalance data classification problems, the syntactic minority oversampling technique (SMOTE) was used to balance the dataset. The overall accuracy was 99.72% with a balanced dataset in the jackknife test by using the optimized combination feature SAAC+DC+CTF+PseACS, which was 4.81% higher than the imbalanced dataset with the same combination feature. The Sn, Sp, Acc, and MCC of HSP families in our predictive model were higher than those in existing methods. This improved method may be helpful for protein function prediction.

Characterization and expression analysis of genes encoding three small heat shock proteins in the oriental armyworm, Mythimna separata(Walker).

Small heat shock proteins (sHsps) function in the response of insects to abiotic stress; however, their role in response to biotic stress has been under-investigated. Mythimna separata, the oriental armyworm, is polyphenetic and exhibits gregarious and solitary phases in response to high and low population density, respectively. In this study, three genes were identified encoding sHsps, namely MsHsp19.7, MsHsp19.8 and MsHsp21.4, and expression levels in solitary and gregarious M. separata were compared. The deduced protein sequences of the three MsHsps had molecular weights of 19.7, 19.8 and 21.4 kDa, respectively, and contained a conserved α-crystalline domain. Real-time PCR analyses revealed that the three sHsps were transcribed in all developmental stages and were dramatically up-regulated at the 6th larval stage in gregarious individuals. Expression of the three MsHsps was variable in different tissues of 6th instar larvae, but exhibited consistent up- and down-regulation in the hindgut and Malpighian tubules of gregarious individuals, respectively. In addition, MsHsp19.7 and MsHsp19.8 were significantly induced when solitary forms were subjected to crowding for 36 h, but all three MsHsps were down-regulated when gregarious forms were isolated. Our findings suggest that population density functions as a stress factor and impacts MsHsps expression in M. separata.

Network Analyses of the Differential Expression of Heat Shock Proteins in Glioma.

Heat shock protein (HSP) is a family of highly conserved protein, which exists widely in various organisms and has a variety of important physiological functions. Currently, there is no systematic analysis of HSPs in human glioma. The aim of this study was to investigate the characteristics of HSPs through constructing protein-protein interaction network (PPIN) considering the expression level of HSPs in glioma. After the identification of the differentially expressed HSPs in glioma tissues, a specific PPIN was constructed and found that there were many interactions between the differentially expressed HSPs in glioma. Subcellular localization analysis shows that HSPs and their interacting proteins distribute from the cell membrane to the nucleus in a multilayer structure. By functional enrichment analysis, gene ontology analysis, and Kyoto Encyclopedia of Genes and Genomes pathway analysis, the potential function of HSPs and two meaningful enrichment pathways was revealed. In addition, nine HSPs (DNAJA4, DNAJC6, DNAJC12, HSPA6, HSP90B1, DNAJB1, DNAJB6, DNAJC10, and SERPINH1) are prognostic markers for human brain glioma. These analyses provide a full view of HSPs about their expression, biological process, as well as clinical significance in glioma.

Study on immunological functions of heat shock protein 40 kDa of Schistosoma japonicum

To investigate the immunological functions of heat shock protein 40 kDa of Schistosoma japonicum (SjHSP40). The homology of the SjHSP40 protein sequence was analyzed and the B and T cell epitopes of SjHSP40 were predicted using bioinformatics tools. The full-length SjHSP40 gene was amplified using a PCR assay, and cloned into the prokaryotic expression vector pGEX-6P-1, which was transformed into Escherichia coli BL-21. The protein expression was induced with isopropyl β-D-thiogalactoside (IPDG), and then, the recombinant protein was purified with glutathione-sepharose 4B resin to yield the fusion protein GST-SjHSP40, which was checked with SDS-PAGE and Western blotting. Following immunization with GST-SjHSP40, the serum levels of anti-SjHSP40 IgG antibody and IgG1 and IgG2a subtypes were detected in BALB/c mice using ELISA. In addition, the effect of SjHSP40 on CD4+ T-cell subset differentiation was examined using flow cytometry. SjHSP40 contained 7 potential B cell epitopes and multiple T cell epitopes (CTL epitopes and Th epitopes). The prokaryotic expression plasmid pGEX-6p-1-SjSHP40 was successfully constructed, and the fusion protein GST-SjHSP40 was obtained following IPDG induction and protein purification. Significantly higher serum levels of anti-SjHSP40 IgG, IgG1 and IgG2a antibodies were detected in mice immunized with GST-SjHSP40 than in other groups; however, SjHSP40 showed no remarkable effects on CD4+ T-cell subset differentiation. SjHSP40 may induce specific humoral immune responses in mice; however, it does not affect the balance of Th immune responses. It is suggested that SjHSP40 may be a potential vaccine candidate.

The Heat Shock Protein HSP70 Promotes Th17 Genes’ Expression via Specific Regulation of microRNA

T helper cells type 17 (Th17) are orchestrators of autoimmune conditions, including multiple sclerosis (MS), but mechanisms of Th17 pathogenicity remain unknown. MicroRNAs (miRNA) are known to control T cells. To understand the function of miRNA in Th17, we have established a T cell line, EL4-TCR+, that resembles the expression pattern of the Th17 cells. Subsequently, we have evaluated the crosstalk between miRNA and Th17 genes’ expression using a combination of gene expression profiling, gene expression manipulation, RNA and protein immunoprecipitation, as well as confocal microscopy. We have found that Th17-related miRNA were strongly expressed in EL4-TCR+ cells following the binding of the cluster of differentiation 3 (CD3) component of the T cell receptor (TCR). Furthermore, a specific inhibition of these miRNA resulted in downregulation of the critical Th17 genes’ expression. Surprisingly, this mechanism relied on the function of the stress signal regulator heat shock protein 70 (HSP70). Upon activation, HSP70 co-localized intracellularly with miRNA processing proteins. Precipitation of HSP70 resulted in enrichment of the Th17-associated miRNA. Finally, HSP70 inhibition led to downregulation of the Th17 genes’ expression and ameliorated development of autoimmune demyelination. Our study demonstrated that HSP70 facilitates specific miRNA function leading to Th17 genes’ expression, a mechanism linking stress and autoimmunity.

Peeking from behind the veil of enigma: emerging insights on small heat shock protein structure and function.

This is a short paper on new ways to think about the structure and function of small heat shock proteins (sHSPs), perhaps the most enigmatic family among protein chaperones. The goal is to incorporate new observations regarding the disordered regions of small heat shock proteins (sHSPs) into the large body of structural information on the conserved structural alpha-crystallin domains (ACD) that define the sHSP family. Disordered regions (N-terminal region and C-terminal region or NTR and CTR, respectively) represent over 50% of the sHSP sequence space in the human genome and are refractory to traditional structural biology approaches, posing a roadblock on the path towards a mechanistic understanding of how sHSPs function. A model in which an ACD dimer serves as a template that presents three grooves into which other proteins or other segments of sHSPs can bind is presented. Short segments within the disordered regions are observed to bind into the ACD grooves. There are more binding segments than there are grooves, and each binding event is weak and transient, creating a dynamic equilibrium of tethered and untethered disordered regions. The ability of an NTR to be in dynamic equilibrium between tethered/sequestered and untethered states suggests several mechanistic alternatives that need not be mutually exclusive. New ways of thinking about (and approaching) the intrinsic properties of sHSPs may finally allow the veil of enigma to be removed from sHSPs.

Structural aspects of the human small heat shock proteins related to their functional activities

Small heat shock proteins function as chaperones by binding unfolding substrate proteins in an ATP-independent manner to keep them in a folding-competent state and to prevent irreversible aggregation. They play crucial roles in diseases that are characterized by protein aggregation, such as neurodegenerative and neuromuscular diseases, but are also involved in cataract, cancer, and congenital disorders. For this reason, these proteins are interesting therapeutic targets for finding molecules that could affect the chaperone activity or compensate specific mutations. This review will give an overview of the available knowledge on the structural complexity of human small heat shock proteins, which may aid in the search for such therapeutic molecules.

2-phenylethynesulfonamide inhibits growth of oral squamous cell carcinoma cells by blocking the function of heat shock protein 70.

Oral squamous cell carcinoma (OSCC) is the most common malignancy in the oral cavity, which accounts for >90% of all diagnosed oral cancers. 2-phenylethynesulfonamide (PES) was known as a selective heat shock protein 70 (Hsp70) function inhibitor, which induced cytotoxic effects on various tumor cell types, but showed to be less toxic to normal cells. However, no associated evaluation of PES on OSCC was found. In the present study, the proliferation of OSCC cells treated with PES was analyzed using a CCK-8 assay. The effects of PES on the cell cycle and apoptosis of OSCC cells were determined by flow cytometric analyses. Expression of associated protein was determined by Western blot analysis. The results of the present study showed that PES inhibited the proliferation of OSCC cell lines in vivo and in vitro. PES induced apoptosis and arrested the cell cycle of OSCC cells. PES inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP), baculoviral IAP repeat containing 2 (c-IAP1), phosphorylated AKT (p-AKT), and phosphorylated extracellular signal-regulated kinase (p-ERK). Additionally, knockdown of Hsp70 enhanced the effects of PES. By contrast, overexpression of Hsp70 attenuated the inhibitory effects of PES on cell viability. PES disrupted the interaction between Hsp70 and XIAP. In conclusion, the present study demonstrated that PES suppresses the growth of OSCC cells through Hsp70-dependent mechanism.

Overexpression of Small Heat Shock Protein LimHSP16.45 in Arabidopsis hsp17.6II Mutant Enhances Tolerance to Abiotic Stresses

Organisms can produce heat shock proteins (HSPs) in response to elevated temperatures and other abiotic stresses. However, the function of HSPs, including small heat shock proteins (sHSPs), in stress tolerance is not fully explored. To improve our understanding of sHSPs, we isolated a gene of sHSPs from David lily (Lilium davidii Duchartre) called LimHSP16.45. Results reveal that LimHSP16.45 is a cytosolic class II sHSP. The HSP17.6II of Arabidopsis thaliana belongs to the HSP20 chaperone protein and is similar to Lim16.45HSP of David lily in terms of size and structure. Both genes have a small heat shock-like alpha-crystallin domain (ACD) structure. To further study the function of Lim16.45HSP, we overexpress it in Arabidopsis hsp17.6II mutant. Then, we detect the expression of LimHSP16.45 in transgenic plant under abiotic stresses and analyze the heat tolerance of transgenic plant. In addition, we measure the activity of three antioxidant enzymes (peroxidase, catalase and superoxide dismutase) and the content of soluble sugar and proline in transgenic plants under abiotic stresses.We found that transgenic plant is tolerant to heat and oxidative stresses given its increased survival rate relative to the hsp17.6II and wild type. Moreover, the content of soluble sugar and proline considerably increase in the transgenic plant. These results support the positive role of LimHSP16.45 in response to heat stress in plants. We suspect that LimHSP16.45 enhances plant tolerance to abiotic stresses by stimulating the activity of ROS-scavenging enzymes and other protective enzymes and increasing the synthesis of proline.

Structure, stability and chaperone function of Mycobacterium leprae Heat Shock Protein 18 are differentially affected upon interaction with gold and silver nanoparticles

Gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) have several biomedical applications. However, the effective usage of these two nanoparticles is impeded due to limited understanding of their interaction with proteins including small heat shock proteins (sHSPs). Specifically, no evidences of interaction of these two nanoparticles with HSP18 (an antigenic protein) which is an important factor for the growth and survival of M. leprae (the causative organism of leprosy) are available in the literature. Here, we report for the first time evidences of “HSP18-AuNPs/AgNPs interaction” and its impact on the structure and chaperone function of HSP18. Interaction of citrate-capped AuNPs/AgNPs (~20 nm diameter) to HSP18 alters the secondary and tertiary structure of HSP18 in a distinctly opposite manner; while “HSP18-AuNPs interaction” leads to oligomeric association, “HSP18-AgNPs interaction” results in oligomeric dissociation of the protein. Surface hydrophobicity, thermal stability, chaperone function of HSP18 and survival of thermally stressed E. coli harbouring HSP18 are enhanced upon AuNPs interaction, while all of them are reduced upon interaction with AgNPs. Altogether, our study reveals that HSP18 is an important drug target in leprosy and its chaperone function may possibly plays a vital role in the growth and survival of M. leprae pathogen in infected hosts.

Understanding the Toxin Effects of β-Zearalenol and HT-2 on Bovine Granulosa Cells Using iTRAQ-Based Proteomics.

Simple SummaryZearalenone (ZEA) and T-2 are two important mycotoxins, which have deleterious effects on the health of humans and livestock. ZEA and its derivatives, α-zearalenol and β-zearalenol, disturb the hormonal homeostasis and lead to numerous problems in the reproductive system. The HT-2 toxin, as the primary metabolite of the T-2 toxin, exerts a series of toxic effects on humans and livestock. The T-2 toxin and its metabolite HT-2 toxin induce damages in multiple tissues, which include the reproductive system. However, toxic response profiles of these mycotoxins on bovine ovarian granulosa cells (bGCs) are unclear. In this study, we determined the importance of heat shock proteins, clarified oxidative stress, and the caspase-3 signaling cascade involved in the mycotoxin-treated toxic response. These results could provide new insights for future studies on prevention and treatment of reproductive problems caused by mycotoxins in bovines.Zearalenone (ZEA) and T-2 are the most common mycotoxins in grains and can enter the animal and human food-chain and cause many health disorders. To elucidate the toxic response profile, we stimulated bovine granulosa cells (GCs) with β-zearalenol or HT-2. Using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic, 178 and 291 differentially expressed proteins (DEPs, fold change ≥ 1.3 and p-value < 0.05) in β-zearalenol and HT-2 groups were identified, respectively. Among these DEPs, there were 66 common DEPs between β-zearalenol and HT-2 groups. These 66 DEPs were associated with 23 biological processes terms, 14 molecular functions terms, and 19 cellular components terms. Most heat shock proteins (HSPs) were involved in the toxic response. Reactive oxygen species accumulation, the endoplasmic reticulum (ER)-stress related marker molecule (GRP78), and apoptosis were activated. β-zearalenol and HT-2 inhibited oestradiol (E2) production. These results emphasized the important function of HSPs, clarified oxidative stress, and demonstrated the caspase-3 signaling cascade involved in mycotoxin-treated toxic response, along with decreased E2 production. This study offers new insights into the toxicity of β-zearalenol and HT-2 on ovarian granulosa cells.

Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy.

Heat shock proteins (HSPs) constitute a large family of molecular chaperones classified by their molecular weights, and they include HSP27, HSP40, HSP60, HSP70, and HSP90. HSPs function in diverse physiological and protective processes to assist in maintaining cellular homeostasis. In particular, HSPs participate in protein folding and maturation processes under diverse stressors such as heat shock, hypoxia, and degradation. Notably, HSPs also play essential roles across cancers as they are implicated in a variety of cancer-related activities such as cell proliferation, metastasis, and anti-cancer drug resistance. In this review, we comprehensively discuss the functions of HSPs in association with cancer initiation, progression, and metastasis and anti-cancer therapy resistance. Moreover, the potential utilization of HSPs to enhance the effects of chemo-, radio-, and immunotherapy is explored. Taken together, HSPs have multiple clinical usages as biomarkers for cancer diagnosis and prognosis as well as the potential therapeutic targets for anti-cancer treatment.

Heat-Shock Protein 27 (HSPB1) Is Upregulated and Phosphorylated in Human Platelets during ST-Elevation Myocardial Infarction.

Heat-shock proteins are a family of proteins which are upregulated in response to stress stimuli including inflammation, oxidative stress, or ischemia. Protective functions of heat-shock proteins have been studied in vascular disease models, and malfunction of heat-shock proteins is associated with vascular disease development. Heat-shock proteins however have not been investigated in human platelets during acute myocardial infarction ex vivo. Using two-dimensional electrophoresis and immunoblotting, we observed that heat-shock protein 27 (HSPB1) levels and phosphorylation are significantly increased in platelets of twelve patients with myocardial infarction compared to patients with nonischemic chest pain (6.4 ± 1.0-fold versus 1.0 ± 0.9-fold and 5.9 ± 1.8-fold versus 1.0 ± 0.8-fold; p < 0.05). HSP27 (HSPB1) showed a distinct and characteristic intracellular translocation from the cytoskeletal fraction into the membrane fraction of platelets during acute myocardial infarction that did not occur in the control group. In this study, we could demonstrate for the first time that HSP27 (HSPB1) is upregulated and phosphorylated in human platelets during myocardial infarction on a cellular level ex vivo with a characteristic intracellular translocation pattern. This HSP27 (HSPB1) phenotype in platelets could thus represent a measurable stress response in myocardial infarction and potentially other acute ischemic events.