Synthesis Of Heat Shock Proteins Research Articles

Longevity-modulating effects of symbiosis: insights from Drosophila-Wolbachia interaction.

Microbial communities are known to significantly affect various fitness components and survival of their insect hosts, including Drosophila. The composition of symbiotic microbiota has been shown to change with the host's aging. It is unclear whether these changes are caused by the aging process or, vice versa, they affect the host's aging and longevity. Recent findings indicate that fitness and lifespan of Drosophila are affected by endosymbiotic bacteria Wolbachia. These effects, however, are inconsistent and have been reported both to extend and shorten longevity. The main molecular pathways underlying the lifespan-modulating effects of Wolbachia remain unclear, however insulin/insulin-like growth factor, immune deficiency, ecdysteroid synthesis and signaling and c-Jun N-terminal kinase pathways as well as heat shock protein synthesis and autophagy have been proposed to play a role. Here we revise the current evidence that elucidates the impact of Wolbachia endosymbionts on the aging processes in Drosophila.

Differential expression pattern of heat shock protein 70 gene in tissues and heat stress phenotypes in goats during peak heat stress period.

It has been established that the synthesis of heat shock protein 70 (Hsp70) is temperature-dependent. The Hsp70 response is considered as a cellular thermometer in response to heat stress and other stimuli. The variation in Hsp70 gene expression has been positively correlated with thermotolerance in Drosophila melanogaster, Caenorhabditis elegans, rodents and human. Goats have a wide range of ecological adaptability due to their anatomical and physiological characteristics; however, the productivity of the individual declines during thermal stress. The present study was carried out to analyze the expression of heat shock proteins in different tissues and to contrast heat stress phenotypes in response to chronic heat stress. The investigation has been carried out in Jamunapari, Barbari, Jakhrana and Sirohi goats. These breeds differ in size, coat colour and production performance. The heat stress assessment in goats was carried out at a temperature humidity index (THI) ranging from 85.36-89.80 over the period. Phenotyping for heat stress susceptibility was carried out by combining respiration rate (RR) and heart rate (HR). Based on the distribution of RR and HR over the breeds in the population, individual animals were recognized as heat stress-susceptible (HSS) and heat stress-tolerant (HST). Based on their physiological responses, the selected animals were slaughtered for tissue collection during peak heat stress periods. The tissue samples from different organs such as liver, spleen, heart, testis, brain and lungs were collected and stored at -70°C for future use. Hsp70 concentrations were analyzed from tissue extract with ELISA. mRNA expression levels were evaluated using the SYBR green method. Kidney, liver and heart had 1.5-2.0-fold higher Hsp70 concentrations as compared to other organs in the tissue extracts. Similarly, the gene expression pattern of Hsp70 in different organs indicated that the liver, spleen, brain and kidney exhibited 5.94, 4.96, 5.29 and 2.63-fold higher expression than control. Liver and brain tissues showed the highest gene expression at mRNA levels as compared to kidney, spleen and heart. HST individuals had higher levels of mRNA level expression than HSS individuals in all breeds. The Sirohi breed showed the highest (6.3-fold) mRNA expression levels as compared to the other three breeds, indicating the better heat stress regulation activity in the breed.

The Heat Stress Response and Diabetes: More Room for Mitochondrial Implication.

Heat preconditioning is a rapid cellular adaptive mechanism shared by many cells/ organs / organisms that results in synthesis and accumulation of heat shock proteins (HSPs), which are responsible for increased tolerance and survival of animals during and after heat stress (HS). HSPs function as molecular chaperones by restoring cellular homeostasis and promoting cell survival, and their major functions include protection of cells from injury by preventing protein damage and aggregation. Abundant evidence points to the ability of one kind of stress caused by external factors that induce primary adaptations in the organism to provide protection against additional stress of the same or another type, a phenomenon known as cross-tolerance. Diabetes mellitus (DM) is one of the diseases which have been associated with increased tissue sensitivity and vulnerability due to incorrect protein folding. Thus, HSPs may play an important role in minimizing the protein damage that can occur under the stressful conditions created by the disease. By increasing HSP production, heat preconditioning may be a promising therapy for patients with lifestylerelated diseases such as hypercholesterolemia, hypertension, DM and obesity. Also, pancreatic β-cells exposed to acute HS activate defence mechanisms which include HSP synthesis and are less sensitive to the effects of cytotoxic agents such as NO, oxygen radicals and β-cytotoxic diabetogenic agents, such as streptozotocin (STZ). Mitochondrial dysfunction and mitochondria-specific cell stress are associated and can even be a primary abnormality caused by DMinduced hyperglycaemia and oxidative stress. There are an increasing number of genetic and/or pharmacological modulations of HSPs that have revealed the connection between HSPs, mitochondria and diabetes. HSPs may affect mitochondrial function in multiple ways, but the influence on skeletal muscle and adipose tissue, as well as on the pancreas, has attracted most interest as a key element in the development of novel pharmacological approaches to treating DM and associated metabolic conditions.

Passive Heating As An Option For Improving Glucose Control

Obesity and type 2 diabetes are increasing in prevalence and can be treated by lifestyle interventions such as diet and exercise. Acute exercise has an insulin sensitising effect, leading to improved glucose control. This may in part be due to the attenuated synthesis of heat shock protein 70 (HSP70) in obesity and diabetes. HSP70 may be elevated by exercise and passive heating (PH). Furthermore, animal studies suggest PH may be beneficial to glucose control. PURPOSE: To determine the effect of PH versus exercise on the HSP70 response and glucose control in overweight and lean humans. METHODS: In a crossover design, ten physically inactive males (5 lean (L) BMI = 23.5 kg.m-2, fat mass = 9.5 ± 4.8 kg; 5 overweight (OW) BMI = 28.0 kg.m-2, fat mass = 20.9 ± 5.3 kg) underwent 60 minutes of exercise at a fixed rate of metabolic heat production (EX, 7.5W.kg-1). In a second trial, participants underwent PH (2.0 W.kg-1) matched to EX for duration, core temperature (Tc) increase and dietary intake. A venous blood sample was obtained before and immediately following heating for analysis of HSP70. Continuous glucose monitoring was used to measure interstitial glucose for the subsequent 24 hours. RESULTS: There were no differences in ΔTc between groups (L = 0.87 ± 0.23°C; OW = 0.85 ± 1.7°C, p = 0.784) or conditions (Ex = 0.8 ± 0.2°C, PH = 0.9 ± 0.2°C, p = 0.913) following heating. Resting HSP70 was negatively correlated with fat mass (r=-0.528, p<0.05). There was a trend between ΔHSP70 and fat mass (r=-0.303, p = 0.194). HSP70 increased 6.8% after heating (p<0.05) with a greater increase in L (0.40 ± 0.44 ng.mL-1) compared to OW (-0.26 ± 0.27 ng.mL-1, p<0.05) after PH but no difference in ΔHSP70 between L and OW following EX. There was no difference in glucose area under the curve between PH and EX, but peak glucose in the first meal following heating was lower for PH (6.7 ± 1.4 mmol.L-1 vs. 7.4 ± 1.2 mmol.L-1; p<0.05). CONCLUSION: The HSP70 response after PH is impaired in OW compared to L and appears linked to fat mass. As PH resulted in no increase in HSP70 in OW, this suggests a need for greater inflammatory stimulus from muscular contraction to elicit rises in HSP70 in OW. PH reduces peak glucose excursions in the first meal after heating and may contribute to improved insulin sensitivity following repeated acute PH exposures, which warrants future investigation.

Purification, crystallization and X-ray diffraction analysis of the DNA-binding domain of human heat-shock factor 2.

Cells respond to various proteotoxic stimuli and maintain protein homeostasis through a conserved mechanism called the heat-shock response, which is characterized by the enhanced synthesis of heat-shock proteins. This response is mediated by heat-shock factors (HSFs). Four genes encoding HSF1-HSF4 exist in the genome of mammals. In this protein family, HSF1 is the orthologue of the single HSF in lower eukaryotic organisms and is the major regulator of the heat-shock response, while HSF2, which shows low sequence homology to HSF1, serves as a developmental regulator. Increasing evidence has revealed biochemical properties and functional roles that are unique to HSF2, such as its DNA-binding preference and sumoylation patterns, which are distinct from those of HSF1. The structural basis for such differences, however, is poorly understood owing to the lack of available mammalian HSF structures. The N-terminal DNA-binding domain (DBD) is the most conserved functional module and is the only crystallizable domain in HSFs. To date, only HSF1 homologue structures from yeast and fruit fly have been determined. Along with extensive studies of the HSF family, more structural information, particularly from members with a remoter phylogenic relationship to the reported structures, e.g. HSF2, is needed in order to better understand the detailed mechanisms of HSF biology. In this work, the recombinant DBD (residues 7-112) from human HSF2 was produced in Escherichia coli and crystallized. An X-ray diffraction data set was collected to 1.32 Å resolution from a crystal belonging to space group P212121 with unit cell-parameters a = 65.66, b = 67.26, c = 93.25 Å. The data-evaluation statistics revealed good quality of the collected data, thus establishing a solid basis for the determination of the first structure at atomic resolution in this protein family.

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

The phenomenon of ischemic preconditioning based on the S.P. Botkin’s idea about defense effect of disturbing factors acting in small intensities is observed in the review. The modern literature data about main types of preconditioning exposure, triggers and mechanisms of ischemic preconditioning are reviewed. This phenomenon was supported in many experiments in vivo and in vitro on animals of different spices as well as in humans in clinical conditions. Ischemic preconditioning is qualified as transient positive changes in the organs and tissues produced by activation of rapid endogenous adoptive processes in them during the short period of subletal ischemia and reperfusion and which defend them from subsequent ischemic episodes. There are early and late ischemic preconditioning (the second window of defense). The first type of ischemic preconditioning belongs to classic type of preconditioning and is produced by the short ischemic episodes (3-5 min) and similar intervals of reperfusion. Ischemic preconditioning observed in a day or more after preconditioning stimuli is named as late preconditioning with genes expression, synthesis of heat shock proteins (HSP 72 in particular) and NO synthase as the basis mechanisms underlying of it. Administration of triggers like adenosine, forbol ether, bradykinine or glycerol derivatives into the blood or ischemic tissues produces defense action similar to ischemic preconditioning and qualified as pharmacological preconditioning. Preconditioning induced by pharmacological agents are more preference than short ischemic episodes. Antihypoxic effects of benzimidazol derivatives in both an acute hypoxia and hypoxic preconditioning are described in the article. Other perspectives of pharmacological preconditioning in practical use are also discussed.

Drought priming induces thermo-tolerance to post-anthesis high-temperature in offspring of winter wheat

High temperature stress is a worldwide environmental constraint on crop production. Exposure of plants to a stress event could induce tolerance in them and even in their offspring to subsequent stresses. This study was to test the hypothesis that drought priming of parent plants could trigger a cross tolerance to high-temperature stress in their offspring. Winter wheat plants were used and were firstly subjected to a drought stress during grain filling, and their offspring were exposed to a post-anthesis high-temperature stress. Grain yield, photosynthesis, anti-oxidation, and proteomic profile in wheat flag leaves of the offspring were determined. The results showed a less yield loss in the next generation of the wheat plants that had received drought priming, which could be ascribed to the improved photosynthesis because of the up-regulated expression of proteins involved in the light reaction and in the Calvin cycle, and to the enhanced anti-oxidation capacity as exemplified by the decreased contents of MDA and H2O2 because of the improved activities of SOD and POD. In addition, the proteomic analysis suggested that the enhanced thermo-tolerance could also be attributed to the more robust signal perception and transduction, better maintenance of protein structures, up-regulation of sucrose synthesis and accumulation of heat shock proteins.

Expression pattern of heat shock proteins during acute thermal stress in the Antarctic sea urchin, Sterechinus neumayeri

Antarctic marine organisms have evolved a variety of physiological, life-history and molecular adaptations that allow them to cope with the extreme conditions in one of the coldest and most temperature-stable marine environments on Earth. The increase in temperature of the Southern Ocean, product of climate change, represents a great challenge for the survival of these organisms. It has been documented that some Antarctic marine invertebrates are not capable of generating a thermal stress response by means of an increase in the synthesis of heat shock proteins, which could be related with their low capacity for acclimatization. In order to understand the role of heat shock proteins as a compensatory response in Antarctic marine species to projected scenarios of increased seawater temperatures, we assessed the expression of the genes Hsp90, Grp78, Hyou1 and Hsc70 in the Antarctic sea urchin Sterechinus neumayeri under three thermal treatments (1 °C, 3 °C and 5 °C), for a period of exposure of 1, 24 and 48 h. The results obtained showed that these genes were expressed themselves in all of the tissues analyzed in a constitutive form. During acute thermal stress, an overexpression of the Hsp90, Grp78 and Hyou1 genes was observed in coelomocyte samples at 3 °C after 48 h, while in esophageal samples, an increase in Hsp90 and Grp78 expression was observed after 48 h. Thermal stress at 5 °C, in general, did not produce a significant increase in the expression of the genes that were studied. The expression of Hsp70 did not show modifications in its expression as a result of thermal stress. S. neumayeri is capable of overexpressing stress proteins as a result of thermal stress, however, this response is delayed and to a lesser degree compared to other Antarctic or temperate species. These results indicate that adult individuals could cope with the expected impacts caused by an increase in coastal sea temperatures in the Southern Ocean.

Molecular cloning of hsf1 and hsbp1 cDNAs, and the expression of hsf1, hsbp1 and hsp70 under heat stress in the sea cucumber Apostichopus japonicus.

The heat shock response (HSR) is known for the elevated synthesis of heat shock proteins (HSPs) under heat stress, which is mediated primarily by heat shock factor 1 (HSF1). Heat shock factor binding protein 1 (HSBP1) and feedback control of heat shock protein 70 (HSP70) are major regulators of the activity of HSF1. We obtained full-length cDNA of genes hsf1 and hsbp1 in the sea cucumber Apostichopus japonicus, which are the second available for echinoderm (after Strongylocentrotus purpuratus), and the first available for holothurian. The full-length cDNA of hsf1 was 2208bp, containing a 1326bp open reading frame encoding 441 amino acids. The full-length cDNA of hsbp1 was 2850bp, containing a 225bp open reading frame encoding 74 amino acids. The similarities of A. japonicus HSF1 with other species are low, and much higher similarity identities of A. japonicus HSBP1 were shared. Phylogenetic trees showed that A. japonicus HSF1 and HSBP1 were clustered with sequences from S. purpuratus, and fell into distinct clades with sequences from mollusca, arthropoda and vertebrata. Analysis by real-time PCR showed hsf1 and hsbp1 mRNA was expressed constitutively in all tissues examined. The expression of hsf1, hsbp1 and hsp70 in the intestine at 26°C was time-dependent. The results of this study might provide new insights into the regulation of heat shock response in this species.

The Hsp70 response of Anguillicola species to host-specific stressors.

The present study is based on infection experiments of two different swim bladder parasite species, Anguillicola crassus Kuwahara et al., 1974 and Anguillicola novaezelandiae Moravec and Taraschewski, 1988, which were experimentally transferred to the two eel species Anguilla anguilla Linnaeus, 1758 and Anguilla japonica Temmink and Schlegel, 1846, respectively. The host-parasite groups were selected due to their different grades of mutual adaptation. The main aim of this study was to analyze the stress responses within the parasites, which were confronted with different hosts, i.e. with different stressors related to the respective host. For this purpose, mean intensities, recovery rates, larvae output, and levels of synthesized heat shock proteins (Hsp70) were determined in nematodes of each infection group. Increased stress responses were detected in the endemic system of A. crassus parasitizing A. japonica and A. crassus in its recently acquired host A. anguilla, which seems to be associated with the immune response of the particular host species and the expenditure of energy on producing larvae. A. novaezelandiae showed overall weak activities in its unknown host species A. japonica, with the lowest recovery rate of all examined groups neither featuring elevated Hsp responses, nor a high mean intensity, nor any reproductive output. On the contrary, in A. anguilla, the parasite reached higher recovery rates, mean intensities, and reproductive output, but no increased Hsp70 levels could be detected. The four considered factors proved partially interdependent, whereas few results did not follow a clear pattern.

Paeoniflorin, a novel heat-shock protein inducing compound, and human myometrial contractility in vitro.

Heat shock proteins (HSPs) are synthesized in virtually all organisms in response to increases in temperature. They are associated with a relaxant effect on the human myometrium and are present in decreased concentration in the myometrium at the time of labor. Paeoniflorin is derived from Paeonia lactiflora and has been shown to induce the synthesis of HSPs in cultured mammalian cells. The purpose of the study was to evaluate the effect of paeoniflorin on human uterine contractility. Samples of human myometrium were taken at lower segment cesarean section. Dissected muscle strips were suspended under isometric conditions and exposed to cumulative additions of paeoniflorin in concentrations ranging from 1 nmol/L to 10 mol/L. Control experiments were simultaneously performed. Paeoniflorin was found to exert an inhibitory effect on spontaneous and agonist-induced contractions compared to control strips. The mean maximal inhibition values were: 42.21% ± 9.26 for spontaneous contractions (n = 6; P < 0.0001) and 47.84% ± 9.05 for oxytocin-induced contractions (n = 6; P < 0.0001). The HSP inducing compound, paeoniflorin, had a relaxant effect on human uterine contractility in vitro. These results reinforce the fact that HSPs may play a physiological role in the onset of labor and may also provide future targets for novel tocolytic treatments.

Mechanisms of heat tolerance in crop plants

Due to possible climate changes, heat stress has obtained a serious concern all over the world. Tolerance to this stress via knowledge of metabolic pathways will help us in engineering heat tolerant plants. A group of proteins called heat shock proteins are synthesized following stress and their synthesis is regulated by transcription factors. Under high temperature (HT), reactive oxygen species (ROS) are often induced and can cause damage to lipids, proteins, and nucleic acids. To scavenge the ROS and maintain cell membrane stability, synthesis of antioxidants, osmolytes, and heat shock proteins is of a vital importance. In view of above mentioned, this review highlights the detailed mechanism of pathways involving crucial steps that change during HT stress.

Hyperthermia effects on Hsp27 and Hsp72 associations with mismatch repair (MMR) proteins and cisplatin toxicity in MMR-deficient/proficient colon cancer cell lines

Purpose: Hyperthermia is used in combination with conventional anticancer agents to potentiate their cytotoxicity. One of its key events is the synthesis of heat shock proteins (HSPs), which are able to associate with components from DNA repair mechanisms. However, little is known about their relationship with the mismatch repair system (MMR). Our aim was to study the effects of hyperthermia on cisplatin (cPt) sensitivity and to determine whether MLH1 and MSH2 associate with Hsp27 and Hsp72 in MMR-deficient(−)/-proficient(+) cells.Materials and methods: HCT116+ch2 (MMR−) and HCT116+ch3 (MMR+) cell lines were exposed to cPt with or without previous hyperthermia (42 °C, 1 h). Clonogenic survival assays, MTT, confocal immunofluorescence, immunoprecipitation, immunoblotting and flow cytometry were performed.Results: Hyperthermia increased the cPt resistance in MMR− cells 1.42-fold. Immunofluorescence revealed that after cPt, Hsp27 and Hsp72 translocated to the nucleus and colocalisation coefficients between these proteins with MLH1 and MSH2 increased in MMR+ cells. Immunoprecipitation confirmed the interactions between HSPs and MMR proteins in control and treated cells. Hyperthermia pretreatment induced cell cycle arrest, increased p73 expression and potentiated cPt sensitivity in MMR+ cells.Conclusions: This is the first report showing in a MMR−/+ cellular model that MLH1 and MSH2 are client proteins of Hsp27 and Hsp72. Our study suggests that p73 might participate in the cellular response to hyperthermia and cPt in a MMR-dependent manner. Further functional studies will confirm whether HSPs cooperate with the MMR system in cPt-induced DNA damage response or whether these protein interactions are only the result of their chaperone functions.

Galacto-oligosaccharides exert a protective effect against heat stress in a Caco-2 cell model

Thermal stress can evoke a stress response and enhance the synthesis of heat shock proteins, while gut barrier dysfunction is considered as an important adverse effect of thermal stress. Considering the previously described effects of galacto-oligosaccharides, nowadays mainly used in infant formulas, we hypothesized that galacto-oligosaccharides may protect the intestinal barrier against heat stress. Human epithelial colorectal adenocarcinoma cells were pre-treated with galacto-oligosaccharides prior to thermal stress exposure (40–42 °C) for 24 h. Pre-treatment of galacto-oligosaccharides prevented the heat stress-induced up-regulation of heat shock proteins and reduced the heat-induced stress response as observed by a decrease in haem oxygenase-1. Galacto-oligosaccharides partly prevented the heat-induced effects on monolayer integrity as measured by transepithelial electrical resistance, paracellular permeability and E-cadherin expression. In addition to their prebiotic effect, galacto-oligosaccharides may have beneficial potency to protect the intestinal epithelial barrier against heat stress and may be an attractive dietary application for people who are at high risk of developing heat stress.

Heat Shock Inhibition of CDK5 Increases NOXA Levels through miR-23a Repression

Hyperthermia is a proteotoxic stress that is lethal when exposure is extreme but also cytoprotective in that sublethal exposure leads to the synthesis of heat shock proteins, including HSP70, which are able to inhibit stress-induced apoptosis. CDK5 is an atypical cyclin-dependent kinase family member that regulates many cellular functions including motility and survival. Here we show that exposure of a human lymphoid cell line to hyperthermia causes CDK5 insolubilization and loss of tyrosine-15 phosphorylation, both of which were prevented in cells overexpressing HSP70. Inhibition of CDK5 activity with roscovitine-sensitized cells to heat induced apoptosis indicating a protective role for CDK5 in inhibiting heat-induced apoptosis. Both roscovitine and heat shock treatment caused increased accumulation of NOXA a pro-apoptotic BH3-only member of the BCL2 family. The increased abundance of NOXA by CDK5 inhibition was not a result of changes in NOXA protein turnover. Instead, CDK5 inhibition increased NOXA mRNA and protein levels by decreasing the expression of miR-23a, whereas overexpressing the CDK5 activator p35 attenuated both of these effects on NOXA and miR-23a expression. Lastly, overexpression of miR-23a prevented apoptosis under conditions in which CDK5 activity was inhibited. These results demonstrate that CDK5 activity provides resistance to heat-induced apoptosis through the expression of miR-23a and subsequent suppression of NOXA synthesis. Additionally, they indicate that hyperthermia induces apoptosis through the insolubilization and inhibition of CDK5 activity.

Translational control of the cytosolic stress response by mitochondrial ribosomal protein L18.

In response to stress, cells attenuate global protein synthesis but permit efficient translation of mRNAs encoding heat shock proteins (HSPs). Despite decades since the first description of the heat shock response, how cells achieve translational control of HSP synthesis remains enigmatic. Here we report an unexpected role for mitochondrial ribosomal protein L18 (MRPL18) in the mammalian cytosolic stress response. MRPL18 bears a downstream CUG start codon and generates a cytosolic isoform in a stress-dependent manner. Cytosolic MRPL18 incorporates into the 80S ribosome and facilitates ribosome engagement on mRNAs selected for translation during stress. MRPL18 knockdown has minimal effects on mitochondria function, but substantially dampens cytosolic HSP expression at the level of translation. Our results uncover a hitherto uncharacterized stress adaptation mechanism in mammalian cells, which involves formation of a “hybrid” ribosome responsible for translational regulation during the cytosolic stress response.

Reproduction reduces HSP70 expression capacity in Argopecten purpuratus scallops subject to hypoxia and heat stress

In scallops, gonad production is highly demanding energetically, and reproduction usually occurs during springsummer, a period of strong environmental changes. The synthesis of heat-shock proteins (HSPs) is a major mechanism of stress tolerance in animals, including scal- lops, and HSP expression contributes considerably to cellular energy demand. Therefore, repro- ductive investment may limit the availability of energy (in terms of ATP) for the expression of HSP in organisms exposed to environmental stress. We evaluated the stress response capacity of adult Argopecten purpuratus scallops to high temperature and hypoxia. Stress response capacity was assessed through gene expression (for temperature stress) and protein induction of 70 kD HSP at 3 reproductive stages: immature, mature and spawned. We also evaluated the effect of reproduc- tive status on the cellular ATP provisioning capacity through citrate synthase activity. Immature scallops exposed to thermal stress showed 1.3- and 1.5-fold increases in hsp70 mRNA and HSP70 protein levels, respectively, and those exposed to hypoxia doubled their level of HSP70 compared to non-stressed immature scallops. However, following gonad maturation and spawning, hsp70 mRNA increased by only 0.49- and 0.65-fold, respectively, after thermal stress and HSP70 protein levels of scallops exposed to thermal and hypoxia stressors did not differ from those of non- stressed animals. In parallel, citrate synthase showed its highest level in immature scallops, declined with gonad maturation, and was lowest in spawned scallops. These results suggest that reproductive investment reduces the stress response capacity of A. purpuratus and that mature and spawned scallops could be more vulnerable to environmental stressors than immature individuals.

Role of heat shock proteins in oral squamous cell carcinoma: A systematic review.

Environmental and patho-physiologic stresses stimulate synthesis of heat shock proteins (HSPs) which enable the cell to survive and recover from stressful conditions, by as yet incompletely understood mechanisms. Heat shock proteins show an increased expression in a wide range of human cancers and have been associated with tumor cell proliferation, differentiation, invasion, metastasis, death, and recognition by the immune system. Yet the role of heat shock proteins in oral cancer is ambiguous. The objective of this review was to systematically assess the data available on the role of HSP expression in oral cancer with special reference to its role in diagnosis, prognosis and treatment. A systematic review of studies that investigated the HSP expression in oral squamous cell carcinoma using Scopus, Medline, Embase and Google scholar databases from their inceptions to 2013, without language restrictions was conducted. We selected 24 studies from which data extraction and validations were performed. The literature search revealed differential expression of HSPs during oral tumorigenesis with implications for the specific role of HSPs in the pathogenesis of oral cancer. HSP expression has been regarded as an independent prognostic factor for oral squamous cell carcinoma patients and HSPs are being explored as potent vehicles for delivery of preventive and treatment vaccines in cancer and other diseases.

Heat-shock protein HSP70 protects neuroblastoma cells SK-N-SH from the neurotoxic effects hydrogen peroxide and the β-amyloid peptide

Neuronal cell death in Alzheimer's disease is associated with the development of oxidative stress caused by the reactive oxygen species (ROS), which can be generated as a result of the effect of beta-amyloid peptides. One of the sources of ROS is hydrogen peroxide, inducing the apoptosis and necrosis of neural tissue cells. The mechanism of hydrogen peroxide apoptotic action includes launching signaling pathways that involve protein kinases PI3K, p38MAPK, JNK and ERK. Oxidative stress leads to increased synthesis of heat-shock proteins in the cells including HSP70. It was shown that the exogenous HSP70 could reduce generation of ROS in cells. In this study, we determined how HSP70 affected apoptosis and necrosis in human neuroblastoma cells SK-N-SH, induced by hydrogen peroxide and β-amyloid peptide Aβ(1-42). It was shown that HSP70 reduces the cytotoxic effects of hydrogen peroxide and beta-amyloid, and protein kinases PI3K and JNK play an important role in the mechanism of HSP70 protective effect on the peroxide induced apoptosis in SK-N-SH cells.

Protective HSP70 Induction by Z-Ligustilide against Oxygen-Glucose Deprivation Injury via Activation of the MAPK Pathway but Not of HSF1.

Heat-shock protein 70 (HSP70) is known to function as a protective molecular chaperone that is massively induced in response to misfolded proteins following cerebral ischemia. The objective of this study was to characterize HSP70 induction by Z-ligustilide and explore its potential role in protection against cerebral ischemia-reperfusion injury. Our results demonstrated that the intranasal administration of Z-ligustilide reduced infarct volume and improved neurological function in a rat stroke model. Meanwhile, Z-ligustilide enhanced the cell viability of PC12 cells insulted by oxygen-glucose deprivation-reoxygenation (OGD-Reoxy) and decreased apoptotic and necrotic cell death. Importantly, Z-ligustilide induced HSP70 expression both in vitro and in vivo. Although heat-shock factor 1 (HSF1) nuclear translocation was promoted by Z-ligustilide, HSP70-based heat-shock element (HSE)-binding luciferase activity was not activated, and HSP70 expression responsive to Z-ligustilide was not attenuated by HSE decoy oligonucleotides. However, Z-ligustilide significantly activated the phosphorylation of mitogen-activated protein kinases (MAPKs). Further inhibition of MAPK activity by specific inhibitors attenuated HSP70 induction by Z-ligustilide. Meanwhile, downregulation of HSP70 using KNK437, an HSP70 synthesis inhibitor, or small hairpin RNA (shRNA) significantly attenuated the protection of Z-ligustilide against OGD-Reoxy-induced injury. Moreover, the application of specific inhibitors of MAPKs also achieved similar results. Finally, Z-ligustilide alleviated the accumulation of ubiquitinated proteins induced by OGD-Reoxy, which was inhibited by HSP70-shRNA. Taken together, our results demonstrated that Z-ligustilide may induce protective HSP70 expression via the activation of the MAPK pathway, but not canonical HSF1 transcription. HSP70 plays a key role in the protection of Z-ligustilide against OGD-Reoxy-induced injury.