Heat Shock Protein 27 Levels Research Articles

Aerobic exercise training improves memory function through modulation of brain-derived neurotrophic factor and synaptic proteins in the hippocampus and prefrontal cortex of type 2 diabetic rats.

Defective insulin signaling in the brain may disrupt hippocampal neuroplasticity resulting in learning and memory impairments. Thus, this study investigated the effect of aerobic exercise training on cognitive function and synaptic protein markers in diabetic rats. Twenty male Wistar rats (200-250g), were fed on high-fat diet and received a low dose of streptozotocin (35mg/kg, i.p) to induce type 2 diabetes. Then diabetic animals were randomly divided into sedentary and training groups. The exercise training program was treadmill running at 27m/min for 60min/day for 8 weeks. One day after the last training session, Morris Water Maze (MWM) task was performed to evaluate spatial learning and memory. Then, the hippocamp and prefrontal cortex tissues were instantly dissected for immunoblotting assay of BDNF, GSK-3β, p-GSK-3β, P38, p-P38, ERK1/2, p-ERK1/2, heat shock protein-27 (HSP27), SNAP-25, synaptophysin, and PSD-95. Independent t-test analysis and two-way ANOVA was used to determine the differences under significance level of 0.05 using the 26th version of IBM SPSS statistical software. The results showed that aerobic exercise improved memory as assessed in the MWM task. Moreover, aerobic exercise up-regulated HSP27 and BDNF protein levels in the prefrontal cortex, and hippocampus coincided with robust elevations in SNAP25 and PSD-95 levels. Moreover, exercise reduced phosphorylated P38, while increased p-ERK1/2 and p-GSK-3β (p). Our findings suggest that aerobic exercise may debilitate the harmful effects of diabetes on the cognitive function possibly through enhancing synaptic protein markers.

Heat Shock Protein 27 Levels Predict Myocardial Inhomogeneities in Hemodialysis Patients.

Background Sudden cardiac death (SCD) is the single major cause of death in hemodialysis (HD) patients. QRS-T angle is an established marker of global repolarization heterogeneity associated with electrical instability and SCD. Heat shock protein 27 (HSP27) plays an important, protective role against noxious factors in the cardiovascular (CV) system. This study is aimed at assessing whether low HSP27 is associated with myocardial inhomogeneities in HD patients, as expressed by increases in the spatial QRS-T angle. Methods Clinical data and biochemical, echocardiographic, and electrocardiographic parameters were evaluated in 182 HD patients. Patients were split into normal and abnormal QRS-T angle groups. Results Patients with abnormally high QRS-T angles were older and had higher prevalence of diabetes as well as myocardial infarction, higher left ventricular mass index (LVMI) and C-reactive protein, worse oxidant/antioxidant status, and lower ejection fraction and HSP27. Multiple regression analysis revealed that abnormal QRS-T values were independently, negatively associated with serum HSP27 and positively associated with LVMI. Conclusions Low HSP27 levels are associated with increased heterogeneity of myocardial action potential, as expressed by increased spatial QRS-T angle.

Up-regulation of androgen receptor by heat shock protein 27 and miR-1 induces pathogenesis of androgenic alopecia.

The pathogenesis of androgenetic alopecia (AGA) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms. A total of 46 male AGA patients (AGA group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected. The levels of DHT and HSP27 in the AGA group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of AGA group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05). HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.

Heat shock protein 27 (HSP27) in patients with ovarian cancer.

Ovarian cancer remains a very common cause of death among women worldwide. The cause is to be found in too late of a diagnostic process and therapeutic difficulties The presence of heat shock proteins in the serum of ovarian cancer patients is still a new area of study. It is necessary to continue studies on the possibilities for using these markers to predict a patient's response to a specific therapy and to monitor treatment progress. The study included 52 women with ovarian cancer, hospitalised at the Department of Obstetrics, Gynaecology and Oncological Gynaecology, Medical University of Silesia. The control group consisted of 25 healthy women. The levels of HSP27 in the studied sera were determined by an immunoenzymatic method (ELISA). The mean concentration of HSP27 in the group of patients with ovarian cancer was significantly higher than in the control group of healthy women. We have shown that mean HSP27 levels in ovarian cancer patients increase with tumour progression and further depend on the clinical stage of the disease (FIGO). Positivity values analysis revealed in all clinical stages of ovarian cancer, excluding stage 1, it was significantly higher than in the control group, and at the 4th stage, it is significantly higher than at the 1st, 2nd, and 3rd stages. However, both for the untreated patients and those patients after chemotherapy, the mean HSP27 levels were significantly higher than in the control group. Our studies indicate a significant contribution of HSP27 to the pathogenesis of ovarian cancer. It seems that serum HSP27 can be a marker for this cancer's development, and a marker for the clinical stage.

Clinical Relevance of Elevated Soluble ST2, HSP27 and 20S Proteasome at Hospital Admission in Patients with COVID-19.

Simple SummarySince the outbreak of the Coronavirus Disease (COVID-19) disease in 2019 immunological research is continuing to debunk contingent pathomechanistic interpretations. Currently the COVID-2019 infection is described in humans as a state of hyperinflammation. As the COVID-2019 pandemic continued we collected serum (first blood draw) from patients that were admitted to the hospital (2020/21). Here we show that proteins that indicate “immune decay” (heat shock protein 27 and 20S proteasome) and immune suppressive soluble suppression of tumorigenicity 2 (sST2) were massively increased in those COVID-19 patients. In addition, we demonstrated that those proteins were associated with mortality, invasive ventilation, and oxygen support. Facit: Our results indicate that COVID-19 disease can also be construed as disease that causes an immunological disintegration. Historically it is notable to report that sepsis pathophysiology underwent a similar metamorphosis. Until 2003 the clinical picture of sepsis was seen as a consequence of a hyperactive immune system. This scientific interpretation tottered, and clinical research has evidenced that septic patients are in a state of immunologic default. Based on our serological data we believe that the concept of “COVID-19 induced hyperinflammation” is ready to undergo a critical appraisal and calls for cytoprotective therapeutic interventions.Although, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) represents one of the biggest challenges in the world today, the exact immunopathogenic mechanism that leads to severe or critical Coronavirus Disease 2019 (COVID-19) has remained incompletely understood. Several studies have indicated that high systemic plasma levels of inflammatory cytokines result in the so-called “cytokine storm”, with subsequent development of microthrombosis, disseminated intravascular coagulation, and multiorgan-failure. Therefore, we reasoned those elevated inflammatory molecules might act as prognostic factors. Here, we analyzed 245 serum samples of patients with COVID-19, collected at hospital admission. We assessed the levels of heat shock protein 27 (HSP27), soluble suppressor of tumorigenicity-2 (sST2) and 20S proteasome at hospital admission and explored their associations with overall-, 30-, 60-, 90-day- and in-hospital mortality. Moreover, we investigated their association with the risk of ventilation. We demonstrated that increased serum sST2 was uni- and multivariably associated with all endpoints. Furthermore, we also identified 20S proteasome as independent prognostic factor for in-hospital mortality (sST2, AUC = 0.73; HSP27, AUC = 0.59; 20S proteasome = 0.67). Elevated sST2, HSP27, and 20S proteasome levels at hospital admission were univariably associated with higher risk of invasive ventilation (OR = 1.8; p < 0.001; OR = 1.1; p = 0.04; OR = 1.03, p = 0.03, respectively). These findings could help to identify high-risk patients early in the course of COVID-19.

HSP25 Vaccination Attenuates Atherogenesis via Upregulation of LDLR Expression, Lowering of PCSK9 Levels and Curbing of Inflammation.

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Heat Shock Protein 27 Is an Emerging Predictor of Contrast-Induced Acute Kidney Injury on Patients Subjected to Percutaneous Coronary Interventions.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication associated with considerable morbidity and mortality. Heat-shock protein 27 (HSP27) plays a role in the defense of the kidney tissue against various forms of cellular stress, including hypoxia and oxydative stress, both features associated with CI-AKI. The aim of our study was to evaluate a potential predictive value of HSP27 for CI-AKI in patients subjected to percutaneous coronary interventions (PCI). Included were 343 selected patients subjected to PCI. Exclusion criteria were conditions that potentially might influence HSP27 levels. HSP27 serum levels were evaluated prior to PCI, together with serum creatinine, the concentration of which was also evaluated twice at 48 and 72 h post PCI. CI-AKI was diagnosed in 9.3% of patients. Patients in whom CI-AKI was diagnosed were older (p < 0.001), were more often females (p = 0.021), had higher prevalence of diabetes (p = 0.011), hypotension during PCI (p < 0.001), albuminuria (p = 0.004) as well as multivessel disease (p = 0.002), received higher contrast volume (p = 0.006), more often received contrast volume (CV) above the maximum allowed contrast dose (MACD) (p < 0.001), and had lower HSP27 level (p < 0.001). On multivariate analysis, CV > MACD (OR 1.23, p = 0.001), number of diseased vessels (OR 1.27, p = 0.006), and HSP27 (OR 0.81, p = 0.001) remained independent predictors of CI-AKI. Low concentration of HSP27 is an emerging, strong and independent predictor of CI-AKI in patients subjected to PCI.

Paclitaxel increases sensitivity of SKOV3 cells to hyperthermia by inhibiting heat shock protein 27

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment strategy for patients with peritoneal metastasis of ovarian cancer. Heat shock proteins (HSPs) play an important role in cellular stress during HIPEC treatment. The aim of the present study was to investigate whether paclitaxel can exert antitumor effects by inhibiting heat shock protein 27 (HSP27) expression during HIPEC treatment. Cell viability was detected by CCK8 assay. We used Western blot analysis to detect HSP27 expression under hyperthermia conditions with or without paclitaxel in SKOV3 cells. To further examine the role of HSP27 in the apoptosis, Bcl-2, Bax and Caspase-3 protein expression were additionally determined after reducing HSP27 levels using an siRNA strategy, and apoptosis was detected using the Annexin V/PI assay. The upregulation of HSP27 expression was accompanied with a rise in temperature. In addition, HSP27 could promote Bcl-2 expression, inhibit Bax and Caspase-3 expression, reduce the Bax / Bcl-2 ratio markedly in SKOV3 cells. Furthermore, paclitaxel could upregulate the Bax / Bcl-2 ratio by inhibiting HSP27 expression, and in turn, promoting apoptosis due to hyperthermia. Paclitaxel could also promote apoptosis by inhibiting HSP27 in SKOV3 cells. Our results demonstrate a synergistic effect between paclitaxel and hyperthermia at the cellular level.

Soluble heat-shock protein 27 in blood serum is a non-invasive prognostic biomarker for ovarian cancer

ObjectivesOvarian cancer (OC) is the leading cause of death in gynecological oncology, primarily caused by limited prognostic and therapeutic options. The heat shock protein 27 (HSP27) is recognized as a prominent factor in OC, playing a pivotal role in cancer progression machinery such as treatment resistance. Thus, HSP27 may represent an appropriate biomarker for OC diagnosis, prognosis, and therapy response. Materials & methodsExtracellular HSP27 levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples of OC patients (n = 242) and compared to a non-malignant control group without any history of cancer (n = 200). Correlations between serum levels of HSP27 and clinical pathological parameters were analyzed by bivariate analysis. Survival analyses were carried out by Kaplan-Meier test. ResultsThis study demonstrated that protein levels of HSP27 are comparable in the blood serum of healthy women and OC patients. However, HSP27 levels are significantly correlated with the volume of ascites, residual tumor mass, and age at first diagnosis in OC patients. Notably, elevated levels of HSP27 demonstrate significantly higher overall survival. ConclusionTaken together, our findings demonstrate that high levels of circulating HSP27 in serum are associated with improved overall survival of OC patients. Even though functionality of secreted HSP27 is still unclear, serum levels of HSP27 represent a putative non-invasive prognostic biomarker candidate for OC progression.

HEAT SHOCK PROTEIN 27 IN LARYNGEAL SQUAMOUS CELL CANCER TREATMENT

Heat shock protein 27 (HSP27) belongs to a family of ATP-independent chaperones and plays a fundamental role in cell physiology in various disease states, including cancer. So, it was found that serum HSP27 levels were significantly increased in patients with various tumors, but their significance in laryngeal carcinoma is not well defined.&#x0D; Purpose of the study. Determination and comparison HSP27 serum levels at different stages of special treatment methods in laryngeal cancer patients.&#x0D; Materials and methods. The studies were conducted in 31 patients of laryngeal cancer of T2–3 N0 M0 categories before treatment and at its various stages. The serum HSP27 levels analysis was carried out using the «ELISA» diagnostics test system by enzyme immunoassay.&#x0D; Results. The serum HSP27 levels in patients before treatment and with various types of special treatment are statistically significantly higher than the control values. There was a decrease in serum HSP27 levels in patients after removal of the neoplasm and a slight increase in serum HSP27 levels after completion of radiation therapy.&#x0D; Comparison of initial serum HSP27 values in patients with subsequent relapse of the disease with initial serum HSP27 levels in patients with positive treatment outcomes did not reveal statistically significant differences.&#x0D; Conclusion. The serum HSP27 levels in laryngeal cancer patients are elevated and remain so at all treatment stages. Initial level of serum HSP27 cannot predict tumor recurrence.

Biophysical analyses and functional implications of the interaction between Heat Shock Protein 27 and antibodies to HSP27

Heat Shock Protein 27 (HSP27) is a small molecular chaperone that reduces the development of atherosclerosis by lowering plasma cholesterol levels as well as inflammation. Human studies show an inverse correlation between atherosclerotic burden and HSP27 expression, and are supported by murine models in which augmenting HSP27 levels curbs experimental atherogenesis. Natural HSP27 auto-antibodies (AAb) are found in human plasma, however their role in modulating the athero-protective effects of HSP27 is unknown. The purpose of this study is to characterize the biophysical interaction between human recombinant HSP27 and AAb. A validated polyclonal anti-HSP27 IgG antibody (PAb) was used to mimic natural AAb. Homology modeling and secondary structure prediction tools facilitated the design of HSP27 truncation and phosphorylation mutants. Secondary structural changes were identified using Circular Dichroism (CD) and Dynamic Light Scattering (DLS). Similar to prior structural investigations of HSP27, there was a predominance of α-helical content in the N-terminal truncation and dephosphorylation (“AA”) mutants. The α-crystallin domain (ACD) predominantly consists of β-strands, with the addition of the N-terminal increasing helical content and the C-terminal maintaining β structure. With increasing ratios of PAb to HSP27 β structure abundance and particle size increased, with a similar trend observed with the N-terminus, C-terminus and ACD peptides but an opposite trend with the phosphorylation peptides. Taken together, these studies provide insights into the interaction of HSP27 and its AAb that ultimately may aid in optimizing the design of HSP27 peptidomimetics with anti-atherogenic potential.

Protective effect of HSP27 in atherosclerosis and coronary heart disease by inhibiting reactive oxygen species.

To clarify the mechanism of heat shock protein 27 (HSP27) as a diagnostic biomarker in coronary heart disease (CHD) and atherosclerosis (AS). Expressions of HSP27 in patients with CHD and healthy controls were determined by enzyme-linked immunosorbent assay and the expressions of HSP27 in aortas of patients with CHD and healthy controls were measured by immunohistochemistry. Receiver operating characteristic curve was applied to assess the diagnostic performance of HSP27 in CHD. ApoE-/- mice were included and accordingly grouped. The expressions of HSP27 in AS plaque were measured by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. AS plaque was observed using hematoxylin and eosin staining. DHE was used to detect reactive oxygen species (ROS) levels in aortas. The expressions of mitochondrial apoptosis-related proteins were measured by Western blot analysis. Cell apoptosis was determined by TUNEL staining. HSP27 was highly expressed in patients with CHD than in healthy controls ( P < 0.01). In comparison to the normal group, the model group had increased the relative positive area of HSP27 and higher expressions of HSP27, Bax, caspase-3, and apoptosis index (AI) but decreased Bcl-2 expression in AS plaque, as well as larger plaque areas and elevated ROS levels in the aorta (all P < 0.05). The HSP27-small interfering RNA group had increased expressions of Bax, caspase-3, and AI but decreased Bcl-2 and HSP27 expressions in AS plaque, as well as larger plaque areas, the relative positive area of HSP27 and higher ROS levels in aorta when compared with those in the model group (all P < 0.05). HSP27 exerts its protective role by suppressing ROS and AS progression by inhibiting mitochondria apoptosis pathway in CHD.

Serum heat shock protein 27 levels predict cardiac mortality in hemodialysis patients

BackgroundDecreased heat shock protein 27 (HSP27) participates in many processes that are involved in cardiovascular (CV) disease. The objective of the study was to evaluate if HSP27 level was predictive of mortality as well as to evaluate factors associated with HSP27 level in a group of patients treated with HD.MethodsEnrolled to the study were 202 HD patients. Clinical data, biochemical, echocardiographic, and carotid atherosclerosis parameters were evaluated. Patients were splited into groups on the basis of the cut-off lower and higher 50th percentile of serum HSP27 levels, and were followed-up for 28.68 ± 6.12 months.ResultsNo significant difference was observed between serum HSP27 levels in patients and controls. Low HSP27 patients were older, had higher left ventricular mass index, lower ejection fraction, higher prevalence of diabetes, myocardial infarction and carotid atherosclerosis, higher C-reactive protein level, and worse oxidant/antioxidant status. The multiple regression analysis identified that HSP27 levels were independently, negatively associated with serum oxidized LDL and the number of carotid plaques. Using the Kaplan–Meier analysis it was shown that the cumulative incidences of both CV and sudden cardiac death (SCD) mortality were higher in low HSP27 group in comparison with high serum HSP27 group. A multivariate Cox analysis showed that HSP27 level is an independent and strong predictor of CV as well as SCD mortality.ConclusionsLow serum HSP27 level is independently associated with both CV and SCD mortality but not with all-cause mortality. Low serum HSP27 level is associated with carotid atherosclerosis and oxidative stress.

Heat shock protein 27 promotes cell cycle progression by down-regulating E2F transcription factor 4 and retinoblastoma family protein p130

Heat shock protein 27 (HSP27) protects cells under stress. Here, we demonstrate that HSP27 also promotes cell cycle progression of MRC-5 human lung fibroblast cells. Serum starvation for 24 h induced G1 arrest in these cells, and upon serum refeeding, the cells initiated cell cycle progression accompanied by an increase in HSP27 protein levels. HSP27 levels peaked at 12 h, and transcriptional up-regulation of six G2/M-related genes (CCNA2, CCNB1, CCNB2, CDC25C, CDCA3, and CDK1) peaked at 24-48 h. siRNA-mediated HSP27 silencing in proliferating MRC-5 cells induced G2 arrest coinciding with down-regulation of these six genes. Of note, the promoters of all of these genes have the cell cycle-dependent element and/or the cell cycle gene-homology region. These promoter regions are known to be bound by the E2F family proteins (E2F-1 to E2F-8) and retinoblastoma (RB) family proteins (RB1, p107, and p130), among which E2F-4 and p130 were strongly up-regulated in HSP27-knockdown cells. E2F-4 or p130 knockdown concomitant with the HSP27 knockdown rescued MRC-5 cells from G2 arrest and up-regulated the six cell cycle genes. Moreover, we observed cellular senescence in MRC-5 cells on day 3 after the HSP27 knockdown, as evidenced by increased senescence-associated β-gal activity and up-regulated inflammatory cytokines. The cellular senescence was also suppressed by the concomitant knockdown of E2F-4/HSP27 or p130/HSP27. Our findings indicate that HSP27 promotes cell cycle progression of MRC-5 cells by suppressing expression of the transcriptional repressors E2F-4 and p130.

CLUES TO THE DEVELOPMENT OF THE ANTI-ATHEROSCLEROTIC HEAT SHOCK PROTEIN 27 IMMUNOTHERAPY FROM THE BIOPHYSICAL CHARACTERIZATION OF THE HSP27 IMMUNE COMPLEX

Heat Shock Protein 27 (HSP27) is a 205-amino acid protein with novel anti-atherosclerotic properties that attenuates atherosclerosis by reducing inflammation and lowering cholesterol levels in serum and arterial plaques. Diminished serum HSP27 levels are associated with increased cardiovascular risk. Recently, we demonstrated the presence of anti-HSP27 auto-antibodies (AAB), that potentiate atheroprotection by attenuating inflammatory signaling. For example, as opposed to HSP27 alone, the combination of HSP27 plus the AAB (i.e., the immune complex) appears to dock at the cell membrane, altering the interaction with extracellular inflammatory signaling pathways (e.g., TLR4 mediated activation of NF-kB). As we are currently focusing on the development of HSP27 immunotherapeutics, this study was performed to characterize the structural features of the HSP27-AAB interaction that may be of importance to peptidomimetic design. Homology modelling and secondary structure prediction tools were used to generate design assorted forms of the HSP27 in E.coli. Various biophysical techniques including circular dichroism (CD), dynamic light scattering (DLS), isothermal titration calorimetry (ITC) were used to assess structure and function of these recombinant protein in the presence and absence of an anti-HSP27 polyclonal antibody (PAb; generated in rabbits) that was used to mimic naturally occurring AABs. In vitro, this PAb showed a high degree of fidelity with AABs. The HSP27 C-terminus includes a key conserved alpha crystalline domain with a primary beta sheet structure. The N-terminus is responsible for the formation of larger oligomers. Using ITC we determined that the interaction of HSP27 with PAB was an exothermic reaction (△H = -3.0 x 10-4 cal/mol) with a Ka of 8.9 x10-4 M-1 with an average N valve of 0.5 suggesting 2:1 binding between the PAb and HSP27. Moreover, this interaction markedly increases the beta-sheet content and complex multi-site binding profile. Our study suggests that the formation of the HSP27 immune complex involves a moderately intensity interaction which results in conformational (secondary structure) changes. These structural changes may be of importance in determining the extracellular signalling (e.g., docking with TLR4), and highlight newly exposed HSP27 motifs that will be soon be explored using candidate peptidomimetics that may be of therapeutic value for the treatment of not only atherosclerosis, but inflammation in general.

HSP27 immunization attenuates atherogenesis by markedly reducing plasma PCSK9 and cholesterol levels

Aim: Augmentation of Heat Shock Protein 27 (HSP27) serum levels attenuates experimental atherogenesis in part by reducing cholesterol levels and inflammation. Higher serum HSP27 levels are associated with reduced 5-year risk of cardiovascular events. Recently, we documented the presence of natural antibodies (AABs) to HSP27.

Effect of liposome‑mediated HSP27 transfection on collagen synthesis in alveolar type II epithelial cells.

To investigate the effect of liposome Lipofectamine® 2000‑mediated HSP27 plasmid transfection in A549 human alveolar typeII epithelial cell line on collagen synthesis during transforming growth factor‑β1 (TGF‑β1)‑induced typeII epithelial cell transition to myofibroblasts. Cells were transfected with varying ratios of the Lipofectamine® 2000‑mediated heat shock protein27 (HSP27) plasmid and the transfection efficiency was determined using flow cytometry. The maximum transfection efficacy was confirmed by laser confocal microscopy. HSP gene expression and the most efficient HSP27 plasmid were determined using reverse transcription‑quantitative polymerase chain reaction. Western blot analysis was used to examine HSP27 and collagen expression levels. With a transfection efficiency of 83%, the 8µg:20µl ratio of liposome: Plasmid had the highest transfection levels. Among the four different interference sequences in the HSP27 plasmid, the Dsequence had the highest interference effect with 70% silencing of the HSP27 gene. The expression of typeIandIII collagen in TGF‑β1‑induced transition of A549 human alveolar typeII epithelial cell line to myofibroblasts was significantly downregulated by the successful transfection with HSP27‑interfering plasmid. The expression of typeI andIII collagen in the TGF‑β1‑induced transition of A549 cells to myofibroblasts was significantly downregulated by transfection of A549 cells with HSP27 plasmid D‑interfering sequence and optimal ratio of Lipofectamine®2000 and HSP27 plasmid.

Heat Shock Protein 27(HSP27) in Kidney Disease: Potentials for Diagnosis and Therapy

The small HSP27 is an actin-specific molecular chaperone involved in cytoskeleton architecture, cell migration, metabolism, survival, growth/differentiation, mRNA stabilization, and tumor progression. HSP27 is detected in nearly all cells with different expression levels. A variety of stimuli induce expression and/or phosphorylation of HSP27. HSP27 phosphorylation affects some of its cellular functions as phosphorylation affects HSP27 oligomerization, which in turn has an impact on some of HSP27 functions. HSP27 has been involved in different kidney diseases playing protective and counter-protective roles. HSP27 shows a protective role against several stressors as reactive oxygen species, hypoxia, osmotic stressors, etc. HSP27 and phospho-HSP27 protein levels are increased in stressed and diseased cells. The current review presents HSP27 in the pathogenesis of different kidney diseases as renal injury, fibrosis and renal cell carcinoma, highlights its role as a potential biomarker and offers new therapeutic optionsthrough manipulation of HSP27.

Comparison of GFAP and HSP27 concentrations in acute moderate-intensity aerobic exercise of different duration

Background: Glial fibrillary acidic protein (GFAP) and heat shock protein -27 (HSP27) plasma can be used as the parameters of exercise-induced astrocyte reactivity. The American College of Sports Medicine (ACSM) recommends an exercise of 30 minutes or 10 minutes duration (each performing bout accumulated toward 30 minutes). The aim of this study was to compare GFAP and HSP27 plasma concentrations in young adults undergoing acute moderate-intensity aerobic exercise of different durations (10 minutes vs 30 minutes).Methods: An experimental study with pre-post design was conducted on 22 participants assigned to either 10 minutes or 30 minutes duration of single bout exercise. Blood sampling was performed before and after the exercise. GFAP and HSP27 plasma levels were measured with ELISA methods. Plasma GFAP and HSP27 levels before and after exercise were analyzed using paired t -test, while GFAP and HSP27 levels after exercise between the two groups were processed using unpaired t-test.Results: Plasma GFAP concentration decreased significantly (0,45 ng/mL) after 30 minutes of aerobic exercise (p&lt;0.05). Plasma HSP27 concentration decreased significantly (1,71 ng/mL) after 10 minutes of aerobic exercise (p&lt;0.05). No significant difference in plasma GFAP and HSP27 concentrations between 10 minutes (GFAP=0.49 ng/mL; HSP27=2.09 ng/mL) and 30 minutes duration of exercise (GFAP=0.45 ng/mL; HSP27=1,71 ng/mL).Conclusion: Acute moderate-intensity aerobic exercise with 10- and 30-minutes duration reduces the reactivity of astrocytes indication the increase of the synapse plasticity. The decrease in GFAP concentration occurred after 30 minutes of exercise and the decrease in HSP27 occurred after 10 minutes of exercise. These results showed that the body responds differently to different treatment duration in order to obtain the same effect on the body.

Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients.

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9–25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25–50 µm), large aggregates (50–70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.