Stress Resistance and Adaptation of the Aquatic Invasive Species Tubastraea Coccinea (Lesson, 1829) to Climate Change and Ocean Acidification

A great number of studies published on long-term ocean warming and increased acidification have forecasted changes in regional biodiversity preempted by aquatic invasive species (AIS). The present paper is focused on invasive Tubastraea coccinea (TC), an azooxanthellate AIS coral thriving in regions of the Gulf of Mexico, which has shown an ability to invade altered habitats, including endemic Indo-Pacific T. coccinea (TCP) populations. To determine if invasive TC are more stress resistant than endemic Indo-Pacific T. coccinea (TCP), authors measured tissue loss and heat shock protein 70 (HSP70) expression, using a full factorial design, post exposure to changes in pH (7.5 and 8.1) and heat stress (31 °C and 34 °C). Overall, the mean time required for TCP to reach 50% tissue loss (LD50) was less than observed for TC by a factor of 0.45 (p < 0.0003). Increasing temperature was found to be a significant main effect (p = 0.004), decreasing the LD50 by a factor of 0.58. Increasing acidity to pH 7.5 from 8.1 did not change the sensitivity of TC to temperature; however, TCP displayed increased sensitivity at 31 °C. Increases in the relative density of HSP70 (TC) were seen at all treatment levels. Hence, TC appears more robust compared to TCP and may emerge as a new dominant coral displacing endemic populations as a consequence of climate change.

Attenuation Effect of Radiofrequency Irradiation on UV-B-Induced Skin Pigmentation by Decreasing Melanin Synthesis and through Upregulation of Heat Shock Protein 70

Excess melanin deposition in the skin causes cosmetic problems. HSP70 upregulation decreases microphthalmia-associated transcription factor (MITF) expression, which eventually decreases tyrosinase activity and melanogenesis. Ultraviolet (UV) radiation upregulates p53, which increases the melanocortin receptor (MC1R) and MITF. Furthermore, HSP70 decreases p53 and radiofrequency irradiation (RF) increases HSP70. We evaluated whether RF increased HSP70 and decreased p53, consequently decreasing the MITF/tyrosinase pathway and melanogenesis in UV-B radiated animal skin. Various RF combinations with 50, 100, and 150 ms and 5, 10, and 15 W were performed on the UV-B radiated mouse skin every 2 d for 28 d. When RF was performed with 100 ms/10 W, melanin deposition, evaluated by Fontana–Masson staining, decreased without skin crust formation in the UV-B radiated skin. Thus, we evaluated the effect of RF on decreasing melanogenesis in the HEMn and UV-B radiated skin at a setting of 100 ms/10 W. HSP70 expression was decreased in the UV-B radiated skin but was increased by RF. The expression of p53, MC1R, and MITF increased in the UV-B radiated skin but was decreased by RF. The expression of p53, MC1R, and MITF increased in the α-MSH treated HEMn but was decreased by RF. The decreasing effects of RF on p53, MC1R, CREB and MITF were higher than those of HSP70-overexpressed HEMn. The decreasing effect of RF on p53, MC1R, CREB, and MITF disappeared in the HSP70-silenced HEMn. MC1R, CREB, and MITF were not significantly decreased by the p53 inhibitor in α-MSH treated HEMn. RF induced a greater decrease in MC1R, CREB, and MITF than the p53 inhibitor. Therefore, RF may have decreased melanin synthesis by increasing HSP70 and decreasing p53, thus decreasing MC1R/CREB/MITF and tyrosinase activity.

Mesenchymal Stem Cells Enhance Vascular Endothelial Growth Factor-A, Endothelial Nitric Oxide Synthetase, and HSP70 Expression in Improving Erectile Dysfunction in Streptozotocin-induced Diabetic Rats

This study investigated the therapeutic role of mesenchymal stem cells (MSCs) on erectile function in a diabetes mellitus erectile dysfunction (DMED) rat model by analyzing the expression of endothelial nitric oxide synthetase (eNOS), vascular endothelial growth factor (VEGF), and the 70 kilodalton heat shock proteins (HSP70). MSCs were isolated from umbilical cords (UCs), and their characteristics identified by flow cytometry and osteogenic differentiation analysis. Thirty 8-week-old rats were divided into four groups: sham, control, T1, and T2. After a 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin (STZ) to induce DM. At 8 weeks after STZ injection, rats with DMED were classified into four groups, sham, control group [DMED rats received 500 μL phosphate buffer saline (PBS)]; T1 [DMED rats treated with 500 μL PBS containing 1 × 106 UC-MSCs]; T2 [DMED rats treated with 500 μL PBS containing 2 × 106 UC-MSCs]. Eight weeks after MSCs administration, the rats’ erectile function was measured by cavernous nerve stimulation. The blinded histological and gene expression assessment were used to analyze the eNOS, HSP70 content, and VEGF expression on the penile tissues. MSCs administration, rats in T1 and T2 groups showed a significant enhancement of erectile response that showed a trend of increase of VEGF mRNA level expression was 2.2 ± 0.61 in T2 Group supported with the optimum recovery of eNOS, in which the value of eNOS expression was 20.66% ± 2.32%. While optimum decrease of HSP70 content, the value of HSP70 expression was 15.50% ± 0.90%. IHC results showed that the DMED induction in rats caused a significant decrease of eNOS content in corpus cavernosum tissue. MSCs could ameliorate DMED in rats by increasing VEGF and decreasing HSP70 and eNOS, indicating these cells offer a potential application for DMED patients’ treatment.

Clinicopathological significance of HSP70 expression in gastric cancer: a systematic review and meta-analysis

Background Heat shock protein 70 (HSP70) has been associated with the clinicopathological characteristics and prognosis of many cancers types, implying that it is a potential cancer biomarker. However, no consensus has been reached regarding its clinicopathological and prognostic significance in patients with gastric cancer. To address this gap, we performed a systematic review and meta-analysis. Methods We searched PubMed, Embase, and the Cochrane Library for full-text literature according to the eligibility criteria. We used the odds ratio and hazard ratio as the suitable parameters to evaluate the clinicopathological and prognostic significance of HSP70. The statistical analysis was performed using STATA 15.0. Results After inclusion and exclusion of studies based on the eligibility criteria, data of 1,307 patients with gastric cancer from 9 studies were finally included. The pooled outcomes implied that HSP70 expression was significantly correlated with higher differentiation degrees, intestinal gastric cancer, and lymphovascular invasion but not with age, gender, depth of invasion, Helicobacter pylori infection, lymph node invasion, TNM stages, and metastasis. The pooled HR showed no significant correlation between HSP70 expression and overall survival of gastric cancer patients. Conclusions Our meta-analysis showed that HSP70 plays a complicated role in the development of gastric cancer. It may be directly engaged in tumour differentiation and distant invasion but cannot be considered a biomarker for predicting the prognosis of gastric cancer.

SATB1 Regulates Chromatin Organization and HSP70 Expression in Early Erythropoiesis and Is Downregulated in Models of Diamond Blackfan Anemia

Diamond Blackfan Anemia (DBA) is a rare genetic disease predominantly caused by mutations carried within one of at least 20 ribosomal genes. DBA is characterized by red blood cell aplasia and normal myeloid and megakaryocyte progenitors, indicating that early uncommitted progenitors are relatively unaffected by the mutations. In DBA, the formation of BFU-E colonies and subsequent erythroblasts are severely restricted and indicate a defect in one of the earliest stages of erythroid expansion. To identify critical molecular mechanisms that may regulate early erythropoiesis, we used shRNAs against the ribosomal protein RPS19 (the most commonly mutated gene in DBA) in cord blood derived CD34+ hematopoietic stem and progenitor cells (HSPCs) and performed bulk RNA-seq. After 3 days in an erythroid culture media, the transcriptomes in CD71+ erythroid progenitors were examined. We found that the special AT binding protein 1 (SATB1) was downregulated in RPS19-insufficient HSPCs compared to healthy cord blood HSPCs. SATB1 is modestly expressed in hematopoietic stem cells but is induced during lymphoid expansion and has been previously reported to suppress myeloid/erythroid progenitor (MEP) expansion. Our results showed that maintaining SATB1 expression is required for optimal expansion of MEP progenitors and that the premature loss of SATB1 in DBA contributes to the anemia phenotype. SATB1 binds to 3 specific regions upstream of the 5'UTR of the HSP70 genes and induces the formation of 2 chromatin loops. An enhancer element associates with the proximal promoters of the two HSP70 genes and facilitates the induction of HSP70. In DBA, HSP70 is not induced and contributes to DBA pathogenesis. HSPA1A is induced 4.3-fold while HSPA1B is induced 3.1-fold. Increased expression of the master erythroid transcription factor GATA1 during erythropoiesis occurs in two phases. The first induction precedes a more dramatic induction that accompanies later stages of erythroid differentiation. The absence of SATB1 or HSP70 reduced the earlier GATA1 induction that accompany MEP expansion by 46.1% and 49.3% respectively. The number of MEPs in SATB1 knockdown HSPCs was reduced, resulting in a 24.5% reduction in CD235+ erythroid and 20.8% reduction in CD41+ megakaryocytes. While SATB1-independent effects of RPS19-insufficiency contribute more significantly to erythroid defects in DBA, we have uncovered that SATB1 contributes to regulation of the earliest stages of erythropoiesis by facilitating the induction of HSP70 and subsequent stabilization of an early induction of GATA1. Disclosures No relevant conflicts of interest to declare.

Heat shock protein 70 could enhance porcine epidemic diarrhoea virus replication by interacting with membrane proteins

In this study, we investigated the role of heat shock protein 70 (HSP70) in porcine epidemic diarrhoea virus (PEDV) replication. We found that PEDV infection induced strong HSP70 overexpression in the very early stage of infection. We also confirmed that HSP70 overexpression increased the speed of PEDV replication, resulting in the generation of more virions. In contrast, knockout of HSP70 in cells significantly downregulated PEDV protein expression, resulting in a significant reduction in PEDV replication. Most importantly, we confirmed that among the structural proteins of PEDV, membrane (M) proteins have this important role. We found that membrane proteins control cellular HSP70 expression in PEDV-infected cells. We confirmed HSP70/M complex formation by both immunoprecipitation and immunofluorescence assays. Additionally, PEDV M overexpression induced strong HSP70 expression. All our results clearly confirmed that in PEDV-infected cells, the M protein plays a very important role in PEDV replication in collaboration with HSP70.

The effect of red-fleshed pitaya (Hylocereus polyrhizus) on heat shock protein 70 and cortisol expression in strenuous exercise induced rats

Background: Oxidative stress from exercise can contribute to damaging cells, increasing heat shock protein 70 (HSP70) and suppressing the immune system in the body. This research aimed to determine the antioxidant potential of red-fleshed pitaya extract on HSP70 and cortisol expression in rats which were subjected to strenuous exercise. Methods: The subjects of this research were 32 Sprague Dawley male rats, aged 3 months, with an average weight of 200 g. Red-fleshed pitaya extract was obtained from methanol extraction process; a maceration technique was performed and the extract was concentrated using an air-drying method. Rats were randomly divided into four groups. Group 1 were subjected to strenuous exercise and treated with distilled water only; while Groups 2, 3 and 4 were subjected to strenuous exercise and treated with 100 mg/kg body weight, 200 mg/kg body weight and 300 mg/kg body weight of red-fleshed pitaya extract, respectively. Strenuous exercises in rats was performed by intense swimming of 20 min/day, 3 days a week for 3 weeks. HSP70 expression and cortisol were measured with Enzyme-Linked Immune Sorbent Assay (ELISA) method. Results: There was a significant reduction of HSP70 (p=0.000) and cortisol expression (p=0.000) between the groups. Also, there was a significant difference in the average decreasing of HSP70 expression between group 4 and either groups 1 or 2 (p=0.000). However, a significant difference between groups 4 and 3 was not observed (p=0.813). Lastly, a significant difference was found in the average decrease of cortisol expression between groups 4 and 1 (p=0.000), 2 (p=0.000), and 3 (p=0.000) respectively. Conclusion: Red-fleshed pitaya is potential to be utilized as antioxidant to decrease the HSP70 and cortisol expression.

A standardized extract of Asparagus officinalis stem improves HSP70-mediated redox balance and cell functions in bovine cumulus-granulosa cells

Heat shock (HS) protein 70 (HSP70), a well-known HS-induced protein, acts as an intracellular chaperone to protect cells against stress conditions. Although HS induces HSP70 expression to confer stress resistance to cells, HS causes cell toxicity by increasing reactive oxygen species (ROS) levels. Recently, a standardized extract of Asparagus officinalis stem (EAS), produced from the byproduct of asparagus, has been shown to induce HSP70 expression without HS and regulate cellular redox balance in pheochromocytoma cells. However, the effects of EAS on reproductive cell function remain unknown. Here, we investigated the effect of EAS on HSP70 induction and oxidative redox balance in cultured bovine cumulus-granulosa (CG) cells. EAS significantly increased HSP70 expression; however, no effect was observed on HSP27 and HSP90 under non-HS conditions. EAS decreased ROS generation and DNA damage and increased glutathione (GSH) synthesis under both non-HS and HS conditions. Moreover, EAS synergistically increased HSP70 and HSF1 expression and increased progesterone levels in CG cells. Treatment with an HSP70 inhibitor significantly decreased GSH level, increased ROS level, and decreased HSF1, Nrf2, and Keap1 expression in the presence of EAS. Furthermore, EAS significantly increased progesterone synthesis. Thus, EAS improves HSP70-mediated redox balance and cell function in bovine CG cells.

The effect of temozolomide on Hsp60 and Hsp70 expression in extracellular vesicles derived from U87MG glioma cells

Objectives Temozolomide (TMZ) is an effective drug for glioblastoma multiforme (GBM), but the mechanism underlying TMZ resistance is poorly understood. New evidence has revealed that the release of heat shock proteins (Hsps) derived from extracellular vesicles (EVs) play an important role in cancer progression by modulating tumor microenvironment and cellular cross-talk. This study aims to evaluate the effects of TMZ on the expression of EV-derived and cellular Hsps and cell motility in U87MG human glioblastoma cell line. Methods Glial-EVs were isolated from the culture medium and characterized by SEM and immunoblotting. The effect of TMZ treatments (25, 200 and 750 µM) on cell proliferation (MTT assay), migration (scratch assay), and Hsp60 and Hsp70 levels (immunoblotting) were evaluated. Results TMZ treatments led to an increase in intracellular Hsp70 while decreasing EV-derived Hsp70. Cellular Hsp60 level was elevated at the low dose of TMZ, but it reduced at higher TMZ concentrations. Hsp60 was also decreased in EVs secreted from TMZ-treated cells. Besides, TMZ treatment reduced the proliferation and migration of glioma cells in a dose-dependent manner. Conclusions Our results suggest that TMZ has the potential to target both EV-derived and cellular Hsps for GBM treatment, thus it may reduce cell motility.