Role Of Heat Shock Proteins Research Articles

Role of heat shock proteins 70/90 in exercise physiology and exercise immunology and their diagnostic potential in sports.

Heat shock proteins (HSPs) are molecular chaperones facilitating the unfolding or folding of secondary structures of proteins, their client proteins, in cellular stress situations. Various internal and external physiological and mechanical stress factors induce a homeostatic imbalance, followed by an increased expression of HSP70 and HSP90. Exercise is a stress factor, too, and its cumulative physiological perturbation manifests at a cellular level by threatening the protein homeostasis of various cell types. Consequently, an increase of HSP70/90 was described in plasma and mononuclear cells and various organs and tissues, such as muscle, liver, cardiac tissue, and brain, after an acute bout of exercise. The specific response of HSP70/90 seems to be strongly related to the modality of exercise, with several dependent factors such as duration, intensity, exercise type, subjects' training status, and environmental factors, e.g., temperature. It is suggested that HSP70/90 play a major role in immune regulation and cell protection during exercise and in the efficiency of regeneration and reparation processes. During long-term training, HSP70/90 are involved in preconditioning and adaptation processes that might also be important for disease prevention and therapy. With regard to their highly sensitive and individual response to specific exercise and training modalities, this review discusses whether and how HSP70 and HSP90 can be applied as biomarkers for monitoring exercise and training.

HSPA12A targets the cytoplasmic domain and affects the trafficking of the Amyloid Precursor Protein receptor SorLA

SorLA and Sortilin are multifunctional receptors involved in endocytosis and intracellular sorting of different and unrelated ligands. SorLA has recently attracted much attention as a novel strong risk gene for Alzheimer’s disease, and much effort is currently being put into understanding the underlying molecular mechanism. Trafficking of SorLA and Sortilin are mediated by interacting with AP-1, AP-2, GGA 1-3 and the retromer complex. Although these cytosolic adaptor proteins all bind to both SorLA and Sortilin, a large fraction of intracellular Sortilin and SorLA are located in different subcellular vesicles. This indicates that unknown specialised adaptor proteins targeting SorLA for trafficking are yet to be discovered. We have identified HSPA12A as a new adaptor protein that, among Vps10p-D receptors, selectively binds to SorLA in an ADP/ATP dependent manner. This is the first described substrate of HSPA12A, and we demonstrate that the binding, which affects both endocytic speed and subcellular localisation of SorLA, is mediated by specific acidic residues in the cytosolic domain of SorLA. The identification of the relatively unknown HSPA12A as a SorLA specific interaction partner could lead to novel insight into the molecular mechanism of SorLA, and re-emphasises the role of heat shock proteins in neurodegenerative diseases.

The Role of Heat Shock Proteins in Regulating Receptor Signal Transduction.

Heat shock proteins (Hsp) are a class of stress-inducible proteins that mainly act as molecular protein chaperones. This chaperone activity is diverse, including assisting in nascent protein folding and regulating client protein location and translocation within the cell. The main proteins within the Hsp family, particularly Hsp70 and Hsp90, also have a highly diverse and numerous set of protein clients, which when combined with the high expression levels of Hsp proteins (2%-6% of total protein content) establishes these molecules as "central regulators" of cell protein physiology. Among the client proteins, Hsps regulate numerous signal-transduction and receptor-regulatory kinases, and indeed directly regulate some receptors themselves. This also makes the Hsps, particularly Hsp90, central regulators of signal-transduction machinery, with important impacts on endogenous and drug ligand responses. Among these roles, Hsp90 in particular acts to maintain mature signaling kinases in a metastable conformation permissive for signaling activation. In this review, we will focus on the roles of the Hsps, with a special focus on Hsp90, in regulating receptor signaling and subsequent physiologic responses. We will also explore potential means to manipulate Hsp function to improve receptor-targeted therapies. Overall, Hsps are important regulators of receptor signaling that are receiving increasing interest and exploration, particularly as Hsp90 inhibitors progress toward clinical approval for the treatment of cancer. Understanding the complex interplay of Hsp regulation of receptor signaling may provide important avenues to improve patient treatment.

Heat-shock proteins in diagnosis and treatment: an overview of different biochemical and immunological functions.

Heat-shock proteins (HSPs) have been involved in different functions including chaperone activity, protein folding, apoptosis, autophagy and immunity. The HSP families have powerful effects on the stimulation of innate immune responses through Toll-like receptors and scavenger receptors. Moreover, HSP-mediated phagocytosis directly enhances the processing and presentation of internalized antigens via the endocytic pathway in adaptive immune system. These properties of HSPs have been used for development of prophylactic and therapeutic vaccines against infectious and noninfectious diseases. Several studies also demonstrated the relationship between HSPs and drug resistance as well as their use as a novel biomarker for detecting tumors in patients. The present review describes different roles of HSPs in biology and medicine especially biochemical and immunological aspects.

The role of heat shock protein 90 in regulating pain, opioid signaling, and opioid antinociception.

Heat shock protein 90 (Hsp90) is one of the central signal transduction regulators of the cell. Via client interactions with hundreds of proteins, including receptors, receptor regulatory kinases, and downstream signaling regulators, Hsp90 has a crucial and wide-ranging impact on signaling in response to numerous drugs with impacts on resultant physiology and behavior. Despite this importance, however, Hsp90 has barely been studied in the context of pain and the opioid receptor system, leaving open the possibility that Hsp90 could be manipulated to improve pain therapeutic outcomes, a current area of massive medical need. In this review, we will highlight the known roles of Hsp90 in directly regulating the initiation and maintenance of the pain state. We will also explore how Hsp90 regulates signaling and antinociceptive responses to opioid analgesic drugs, with a special emphasis on ERK MAPK signaling. Understanding this new and growing area will improve our understanding of how Hsp90 regulates signaling and physiology, and also may provide new ways to treat pain, and perhaps reduce the severe impact of the ongoing opioid addiction and overdose crisis.

Triticum aestivum heat shock protein 23.6 interacts with the coat protein of wheat yellow mosaic virus.

The role of heat shock proteins (HSPs) in viral replication has been described in numerous publications. Wheat yellow mosaic virus (WYMV) belongs to the genus Bymovirus (family Potyviridae), which causes yellow mosaic and dwarf symptoms in wheat (Triticum aestivum). In this study, the T. aestivum heat shock protein 23.6 (TaHSP23.6), which belongs to the small heat shock protein family, was shown to interact with the WYMV coat protein (CP) in a yeast two-hybrid screen. The co-localization and interaction between TaHSP23.6 and WYMV CP were additionally verified in Nicotiana benthamiana by co-localization assays and bimolecular fluorescence complementation (BiFC). Not only the transcription of TaHSP23.6 but also that of other HSP family members (TaHSP70, TaHSP90, and TaHSP101) was up-regulated in WYMV-infected leaves, as shown by semi-quantitative PCR assays. Interestingly, the expression levels of the T. aestivum heat stress transcription factor A2 (TaHSFA2) members were varied in response to WYMV infection. Thus, our results provide insights into the interaction between TaHSP23.6 and WYMV infection.

Effects of transfected heat shock protein 70 on cysteinyl aspartate-specific protease-12, C/EBP homologous protein and c-Jun amino-terminal kinase signal pathway in endoplasmic reticulum stress

Objective To study the effect of heat shock protein 70 (HSP70) on cysteinyl aspartate-specific protease (Caspase)-12, C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) signal pathway in the endoplasmic reticulum stress. Methods HSP70 gene was transfected into SD neonatal rat cardiomyocytes by lipofectin. We used SD neonatal rat cardiomyocytes to establish a hypoxia cell model, and then we further detected the role of HSP70 in cell apoptosis, in expression of Casepase-12, CHOP, JNK pathway in ER caused by ER stress, by overexpression or downexpression of HSP70. Results The early apoptosis rate of the blank group (9.28±0.83)%, late (28.60±1.83)%, HSP70 gene transfection group early apoptosis rate (4.30±0.72)%, late (11.6±1.66)%, HSP70 treated with antisense oligonucleotides early apoptosis rate (29.3±2.54)%, late (34.4±2.43)%. Hypoxia-induced cell apoptosis was inhibited by HSP70, but was promoted by HSP70 anti-sense oligonucleotide. Hypoxia-induced ROS production was also inhibited by HSP70, but was not inhibited by HSP70 anti-sense oligonucleotide. HSP70 signifiantly inhibited the expression of Caspase-12 and CHOP. HSP70 increased the expression of JNK. HSP70 anti-sense oligonucleotide significantly increased the expression of CHOP, but did not signifiantly inflent other tested molecules. Conclusion This study demonstrated that HSP70 reduce myocardial cell apoptosis by regulating the Caspase-12, C/EBP homologous protein and c-Jun aminoterminal kinase signal pathway of endoplasmic reticulum. Key words: Cardiomyocyte; Heat shock proteins 70; Endoplasmic reticulum stress; Cysteinyl aspartate-specific protease-12; C/EBP homologous protein; c-Jun N-terminal kinase; Apoptosis

Chemotherapy Sensitizes Therapy-Resistant Cells to Mild Hyperthermia by Suppressing Heat Shock Protein 27 Expression in Triple-Negative Breast Cancer.

Purpose: Triple-negative breast cancer (TNBC) is a clinically aggressive disease with poor prognosis. Conventional chemotherapeutics are generally able to shrink the tumor mass, but often fail to completely eradicate cancer stem-like cells (CSCs) that are responsible for high risk of relapse and frequent metastases. In this study, we examined thermal sensibility of CSCs, developed an approach that enabled concurrent elimination of both the bulk of cancer cells and CSCs, and investigated the underlying mechanism.Experimental Design: We designed a platform consisting of gold nanoparticle-coated porous silicon microparticle (AuPSM) that was also loaded with docetaxel micelles (mDTXs) to enable concurrent killing of the bulk of cancer cells by released mDTX and CSCs by mild hyperthermia upon stimulation of AuPSM with near infrared. In addition, we examined the role of heat shock proteins in sensitizing CSC killing. Finally, we applied mDTX-loaded AuPSM to treat mice with SUM159 and 4T1 orthotopic tumors and evaluated tumor growth and tumor metastasis.Results: MDA-MB-231 and SUM159 TNBC cells treated with mDTX-loaded AuPSM and mild hyperthermia displayed significantly reduced efficiencies in mammosphere formation than those treated with mDTX alone or mild hyperthermia alone. Combination treatment also completely inhibited SUM159 orthotopic tumor growth and 4T1 tumor metastasis. Mechanistically, DTX treatment suppressed expression of heat shock protein 27 in cancer cells including the CSCs, rendering cells sensitive to mild hyperthermia.Conclusions: Our results indicate that chemotherapy sensitizes CSC to mild hyperthermia. We have developed an effective therapeutic approach to eliminate therapy-resistant cells in TNBC. Clin Cancer Res; 24(19); 4900-12. ©2018 AACR.

Possible Role of Heat Shock Protein 70 in Childhood Seizures

Abstract Background There has been a long interest in investigating the relationship between heat shock protein (HSP) expression and the evidence of neuronal damage in the most susceptible brain areas after seizures. So, the present study aimed to assess heat shock protein (HSP70) in children with seizures (febrile seizures and epilepsy), and to find out the cutoff point of this marker that may help in confirming epilepsy diagnosis. The present study has been conducted to evaluate serum levels of HSP70 in children with epileptic and febrile seizures and to compare these results to that of healthy children. Materials and Methods A prospective study included 85 children (32 females and 53 males) in Children and Maternity Unit, Minia University Hospital, Minia, Egypt. Children were subdivided into three groups, group (I) included 30 children with epilepsy, group (II) included 30 children with febrile seizures, and group (III) included 25 healthy children that served as a control group. HSP70 assay was performed for all included children using the enzyme-linked immunosorbent assay technique. Results The overall results revealed significant high serum HSP70 levels in epilepsy and febrile seizures groups when compared with control group (p < 0.001). Also, HSP70 serum levels were significantly higher in epilepsy group than in febrile seizures group (p < 0.001). Serum HSP70 level at a cutoff point > 170 ng/L showed 60% sensitivity and specificity equal to 83.3% in prediction of epilepsy. Conclusion HSP70 level was significantly higher in epileptic and febrile seizures children than normal healthy children, and HSP70 may be beneficial in confirming the diagnosis of epilepsy.

The role of heat shock protein 27 phosphorylation in the proliferation and apoptosis of human umbilical vein endothelial cells induced by Visfatin

ObjectiveTo study the mechanism of heat shock protein 27 (HSP27) phosphorylation in the visfatin-induced proliferation and its protective effect against high-glucose induced apoptosis in HUVECs. MethodsHuman umbilical vascular endothelial cells (HUVECs) were isolated from umbilical veins and treated with visfatin. The proliferation of HUVECs was measured by the MTT assay and the apoptosis of HUVECs was detected by TUNEL assay. The phospho-HSP27 expression was detected by Western blot. The siRNA was used to knock down HSP27 expression in HUVECs. ResultsVisfatin significantly promoted the HUVECs growth and inhibited the high-glucose induced apoptosis of HUVECs in a dose-dependent manner. Also, visfatin upregulated the expression of HSP27 phosphorylation in a time-dependent manner, with a peak at 12 h. Visfatin prompted cell proliferation and exerted a protective effect against high-glucose induced apoptosis in HUVECs, which was significantly blocked by siRNA-HSP27. The HSP27 phosphorylation induced by visfatin was also blocked by the specific PI3K/Akt inhibitor LY294002 and ERK 1/2 inhibitor U0126. Furthermore, the visfatin impact on HUVECs as above were also blocked by LY294002 and U0126. ConclusionVisfatin prompted cell proliferation and exerted a protective effect against high-glucose induced apoptosis in HUVECs through HSP27 phosphorylation. PI3K/Akt and ERK1/2 are important signaling pathways that contribute to HSP27 phosphorylation.

Clinical, Prognostic and Therapeutic Significance of Heat Shock Proteins in Cancer.

Heat Shock Proteins (HSPs) constitute a group of proteins that play a crucial role in the process of protein folding. HSPs are also known to modulate a number of key apoptotic factors. High expression of these proteins is reported in an array of cancers, such as breast, prostate, colorectal, lung, ovarian, gastric, oral and esophageal cancer. Ample amount of investigations were carried out on a variety of cancers suggesting HSPs as a promising hallmark in cancers. Their expression profile in several tumors elucidates that they help in proliferation, invasion, metastasis and death of cancerous cells. Detection of the levels of heat shock proteins and their specific antibodies in the sera of diseased individuals can play an important role in cancer diagnosis. This review will present and summarize latest research being carried out on heat shock proteins. It will also highlight the clinical and prognostic features of HSP27, HSP60, HSP70, HSP90 and HSP110, and will discuss future implications of HSPs in the diagnosis and prognosis of cancer. Furthermore, the role of heat shock proteins as a therapeutic target in cancer will be discussed. In addition, the review article will report various studies, where HSPs have been targeted for their therapeutic potential. In summary, multiple experimental investigations have been successful in suggesting the role of heat shock protein as a clinical biomarker and therapeutic target in cancer. HSPs are associated with a number of cancer hallmarks such as cell proliferation, invasion and metastasis. Inhibition of HSPs has resulted in successful therapeutic outcome in cancer. It has served as a novel anti-cancer therapy for the treatment of several cancer forms. However, more experimental studies are required to elucidate the reliability and efficacy of heat shock proteins in combination with other conventional markers for cancer diagnosis and prognosis. Novel and effective interventions through HSP inhibition are expected to decrease the burden of cancer in the near future.

Role of MAPKs in HSP70's Protection against Heat Stress-Induced Injury in Rat Small Intestine.

Aim To evaluate the role of heat shock protein 70 (HSP70) on the MAPK pathway activation with quercetin treatment and its protection against small intestine impairments of heat stressed rats. Methods Forty-eight male Sprague-Dawley rats aged 6 weeks were randomized to three groups (n=16/group), namely, control (CON), heat stress (HS), and heat stress + quercetin (HQ). The experiment lasted for 14 days with daily 50 min of heat stress treatment (43°C) for the HS and HQ groups. Rats of HQ group were intragastrically given 0.5 ml quercetin solution (50 mg/kg body weight) before the heat stress treatment. Half of the animals were sacrificed on day 7 and the rest on day 14 for tissue sampling. Intestinal morphology, small intestine morphology and permeability, protein expression of HSP70, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and caspase-3 activity were examined. Results Heat stress caused morphological damage to the small intestine and increased intestinal permeability. HSP70 expression and MAPK activity in the small intestine were increased by heat stress. Inhibition of HSP70 by quercetin did not change intestinal permeability compared with the HS group but aggravated intestinal injury and affected the activation of MAPKs and caspase-3. Conclusions HSP70 may modulate stress-activated signaling and acts in a protective manner via MAPK signaling. Affecting HSP70 protective mechanisms could be useful for protection against heat stress-induced injury in rat small intestine.

Quantification of HSP70 Gene Expression and Determination of Capacitation Status of Magnetically Separated Cryopreserved Bovine Spermatozoa at Different Thawing Temperature and Time

The role of heat shock protein in reproduction is widely known as a molecular chaperone in aiding and repairing protein formation when stress occurred. The present objectives were to evaluate the effect of different thawing temperature and time on the expression of HSP70 gene expression and the capacitation status in cryopreserved bovine spermatozoa. Briefly, fresh ejaculates were obtained from three different adult bulls. The semen then underwent a sperm washing technique known as Magnetic Activated Cell Sorting System (MACS) and later on, cryopreserved. The sperm- containing straws were then thawed at five different thawing temperatures and time post-cryostorage; 20°C for 13 s, 37°C for 30 s, 40°C for 7 s, 60°C for 6 s and 80°C for 5 s. The RNA was extracted from each of the sperm’s pellets and converted to cDNA prior to the qPCR process. Capacitation status was then determined by means of CTC assay. The results showed that after the process of amplification, there is a significant different of HSP70 gene expression in MACS process samples when the thawing process was performed at 37°C for 30 s, with p<0.05. Furthermore, the CTC assay also showed that thawing at the same temperature gave less capacitated spermatozoa with p<0.05. As a conclusion, MACS yield spermatozoa with a better expression of HSP70 gene and less capacitated spermatozoa when thawing was done at 37°C for 30 s.

Nitric oxide-mediated cross-talk of proline and heat shock proteins induce thermotolerance in Vicia faba L.

Due to the global warming, rising temperature became a serious threat to the world agriculture. Faba bean plant is very susceptible to heat stress and performs poorly under high temperature condition. Therefore, the performance of faba bean (Vicia faba L.), genotype ‘C5’ was tested to explore (i) the biosynthesis of proline (Pro) in response to heat stress (HS) and the involvement of nitric oxide (NO) and Pro in thermotolerance mechanism and (ii) the role of heat shock proteins (HSPs) and Pro in defense, and their correlation with the tolerance of faba bean plant to HS. Exposure of plants to HS for 48 h resulted in increased levels of reactive oxygen species [hydrogen peroxide (H2O2) and superoxide ions (O2•−)], nitric oxide (NO), accumulation of Pro and malondialdehyde, electrolyte leakage, DNA damage, chlorophyll (Chl) degradation and in decreased leaf relative water content (RWC) and Chl content in faba bean plants. However, at the same time increasing levels of HS (32, 37 and 42 °C) increased the accumulation of NO, Pro, activities of Pro metabolizing enzymes (Δ1-pyrroline-5-carboxylate synthetase, ornithine-δ-aminotransferase and proline dehydrogenase) and expression of HSPs (Hsp17.6, Hsp70, Hsp90-1, and Hsp101). Induced biosynthesis of NO and Pro under HS activated defense system of plants by enhancing the activities of antioxidant enzymes [superoxide dismutase, catalase, glutathione reductase and ascorbate peroxidase] and also by increasing the content of reduced glutathione (GSH), ascorbate (AsA) and oxidized glutathione (GSSG). While, an increase in GSSG content was found lesser than an increase in GSH under HS stress. Application of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO; an NO scavenger) decreased the accumulation of leaf RWC and Pro and NO. Therefore, it can be proposed that NO acts as both signal molecule and promotor of Pro biosynthesis. The present investigation reveals that above studied parameters could be used in identifying a HS-tolerant plant that can be utilized in future breeding programs.

HSP60 critically regulates endogenous IL-1\u03b2 production in activated microglia by stimulating NLRP3 inflammasome pathway

BackgroundInterleukin-1β (IL-1β) is one of the most important cytokine secreted by activated microglia as it orchestrates the vicious cycle of inflammation by inducing the expression of various other pro-inflammatory cytokines along with its own production. Microglia-mediated IL-1β production is a tightly regulated mechanism which involves the activation of nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome pathway. Our previous study suggests the critical role of heat shock protein 60 (HSP60) in IL-1β-induced inflammation in microglia through TLR4-p38 MAPK axis. However, whether HSP60 regulates endogenous IL-1β production is not known. Therefore, to probe the underlying mechanism, we elucidate the role of HSP60 in endogenous IL-1β production.MethodsWe used in vitro (N9 murine microglial cells) and in vivo (BALB/c mouse) models for our study. HSP60 overexpression and knockdown experiment was done to elucidate the role of HSP60 in endogenous IL-1β production by microglia. Western blotting and quantitative real-time PCR was performed using N9 cells and BALB/c mice brain, to analyze various proteins and transcript levels. Reactive oxygen species levels and mitochondrial membrane depolarization in N9 cells were analyzed by flow cytometry. We also performed caspase-1 activity assay and enzyme-linked immunosorbent assay to assess caspase-1 activity and IL-1β production, respectively.ResultsHSP60 induces the phosphorylation and nuclear localization of NF-κB both in vitro and in vivo. It also induces perturbation in mitochondrial membrane potential and enhances reactive oxygen species (ROS) generation in microglia. HSP60 further activates NLRP3 inflammasome by elevating NLRP3 expression both at RNA and protein levels. Furthermore, HSP60 enhances caspase-1 activity and increases IL-1β secretion by microglia. Knockdown of HSP60 reduces the IL-1β-induced production of IL-1β both in vitro and in vivo. Also, we have shown for the first time that knockdown of HSP60 leads to decreased IL-1β production during Japanese encephalitis virus (JEV) infection, which eventually leads to decreased inflammation and increased survival of JEV-infected mice.ConclusionHSP60 mediates microglial IL-1β production by regulating NLRP3 inflammasome pathway and reduction of HSP60 leads to reduction of inflammation in JEV infection.

MODERN IDEAS ABOUT “ATOPIC MARCH” PATHOGENESIS AND POSSIBLE ROLE OF HEAT-SHOCK PROTEINS

Allergic diseases pose a serious health problem worldwide. The review of literature presents some data on the role of heat shock proteins in the pathogenesis of atopic dermatitis and allergic rhinitis, as the most common diseases in the population of this nosological group. Data on the possible role of heat shock proteins in the pathogenesis of atopic march development are also presented.

Role of heat shock protein 70 in chronic pancreatitis: An experimental study

Role of heat shock protein 70 in chronic pancreatitis: An experimental study

The role of heat shock protein 70 in oxidant stress and inflammatory injury in quail spleen induced by cold stress.

The aim of this study was to investigate the role of heat shock protein 70 (Hsp70) in oxidative stress and inflammatory damage in the spleen of quails which were induced by cold stress. One hundred ninety-two 15-day-old male quails were randomly divided into 12 groups and kept at 12 ± 1°C to examine acute and chronic cold stress. We first detected the changes in activities of antioxidant enzymes in the spleen tissue under acute and chronic cold stress. The activities of glutathione peroxidase (GSH-Px) fluctuated in acute cold stress groups, while they were significantly decreased (p < 0.05) after chronic cold stress. The activities of superoxide dismutase (SOD), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) content were decreased significantly (p < 0.05) in both of the acute and chronic cold stress groups. Malondialdehyde (MDA) content was significantly increased (p < 0.05) under cold stress except the 0.5h group of acute cold stress. Besides, histopathological analysis showed that quail's spleen tissue was inflammatory injured seriously in both the acute and chronic cold stress groups. Additionally, the inflammatory factors (cyclooxygenase-2 (COX-2), prostaglandin E synthase (PTGES), iNOS, nuclear factor-kappa B (NF-κB), and tumor necrosis factor-a (TNF-α)) and Hsp70 mRNA levels were increased in both of the acute and chronic cold stress groups compared with the control groups. These results suggest that oxidative stress and inflammatory injury could be induced by cold stress in spleen tissues of quails. Furthermore, the increased expression of Hsp70 may play a role in protecting the spleen against oxidative stress and inflammatory damage caused by cold stress.

The protein-protein interaction network and clinical significance of heat-shock proteins in esophageal squamous cell carcinoma.

Heat-shock proteins (HSPs), one of the evolutionarily conserved protein families, are widely found in various organisms, and play important physiological functions. Nevertheless, HSPs have not been systematically analyzed in esophageal squamous cell carcinoma (ESCC). In this study, we applied the protein-protein interaction (PPI) network methodology to explore the characteristics of HSPs, and integrate their expression in ESCC. First, differentially expressed HSPs in ESCC were identified from our previous RNA-seq data. By constructing a specific PPI network, we found differentially expressed HSPs interacted with hundreds of neighboring proteins. Subcellular localization analyses demonstrated that HSPs and their interacting proteins distributed in multiple layers, from membrane to nucleus. Functional enrichment annotation analyses revealed known and potential functions for HSPs. KEGG pathway analyses identified four significant enrichment pathways. Moreover, three HSPs (DNAJC5B, HSPA1B, and HSPH1) could serve as promising targets for prognostic prediction in ESCC, suggesting these HSPs might play a significant role in the development of ESCC. These multiple bioinformatics analyses have provided a comprehensive view of the roles of heat-shock proteins in esophageal squamous cell carcinoma.

Heat shock protein 70 promotes lipogenesis in HepG2 cells

BackgroundThe increasing prevalence of non-alcoholic fatty liver disease (NAFLD) has followed the international rise in obesity rates. Multiple mechanisms are involved in NAFLD, including endoplasmic reticulum stress and oxidative stress. Heat shock protein 70 (HSP70), which is abundant in most organisms, is sensitive to stress. However, the role of HSP70 in NAFLD has not been investigated. Here, we investigated the possible role of HSP70 in lipid synthesis.MethodsC57BL/6 mice were fed a high-fat diet, and HepG2 cells were treated with 0.5 mM palmitic acid (PA). HSP70 expression was detected by qPCR, Western blot and immunohistochemistry. Total cholesterol (TC) and triglyceride (TG) levels were detected by enzyme-linked immunosorbent assay (ELISA). After Hsp70 overexpression and knockdown, TC and TG levels and FAS, SCD, and ACC expression were detected.ResultsHSP70 expression was significantly increased in the livers of obese mice. In vitro, HSP70 expression was markedly induced by PA in HepG2 cells. Notably, HSP70 overexpression in HepG2 cells enhanced TC and TG synthesis, in parallel with the upregulation of lipogenic genes, including FAS, SCD and ACC. By contrast, HSP70 knockdown decreased the levels of cellular lipids and the expression of FAS, SCD, and ACC in HepG2 cells. Together, our results suggest that HSP70 may promote lipogenesis in HepG2 cells.ConclusionsHeat shock protein 70 promotes lipogenesis in HepG2 cells.