Heat Shock Protein Response Research Articles

Expression of Heat Shock and Other Stress Response Proteins in Ticks and Cultured Tick Cells in Response toAnaplasmaspp. Infection and Heat Shock

Ticks are ectoparasites of animals and humans that serve as vectors of Anaplasma and other pathogens that affect humans and animals worldwide. Ticks and the pathogens that they transmit have coevolved molecular interactions involving genetic traits of both the tick and the pathogen that mediate their development and survival. In this paper, the expression of heat shock proteins (HSPs) and other stress response proteins (SRPs) was characterized in ticks and cultured tick cells by proteomics and transcriptomics analyses in response to Anaplasma spp. infection and heat shock. The results of these studies demonstrated that the stress response was activated in ticks and cultured tick cells after Anaplasma spp. infection and heat shock. However, in the natural vector-pathogen relationship, HSPs and other SRPs were not strongly activated, which likely resulted from tick-pathogen coevolution. These results also demonstrated pathogen- and tick-specific differences in the expression of HSPs and other SRPs in ticks and cultured tick cells infected with Anaplasma spp. and suggested the existence of post-transcriptional mechanisms induced by Anaplasma spp. to control tick response to infection. These results illustrated the complexity of the stress response in ticks and suggested a function for the HSPs and other SRPs during Anaplasma spp. infection.

B12 Treatment with arimoclomol does not lead to rescue of motor or striatal deficits in the YAC128 mouse model of Huntington's disease

BackgroundHuntington's Disease (HD) is an inherited neurological disorder characterised by loss of motor coordination, cognitive dysfunction and psychiatric disturbances that remains without a cure. Arimoclomol, a compound reported to enhance...

MDMA Administration and Heat Shock Proteins Response: Foreseeing a Molecular Link

Molecular and cellular mechanisms of MDMA-induced toxicity have been extensively studied in a number of experimental models. Nevertheless, only few studies investigated the involvement of HSPs ("molecular chaperones") in MDMA organs toxicity. In the present minireview we highlight this subject analysing the results of these studies conducted especially on brain tissue. Despite of it seems obvious that HSPs overexpression is a protective reaction against MDMA treatment, the molecular mechanisms for exerting their action are far to be undiscovered. At the same time, we need of comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after acute and chronic administration of MDMA.

Erratum to: Heat shock protein responses to eccentric weight or treadmill exercise in active young females

Erratum to: Heat shock protein responses to eccentric weight or treadmill exercise in active young females

Interrelationship between lipid droplet (LD) biogenesis and heat shock protein (Hsp) response

Interrelationship between lipid droplet (LD) biogenesis and heat shock protein (Hsp) response

Abrogating HSP Response Augments Cell Death Induced by As2O3 in Glioma Cell Lines

We previously reported that Arsenic trioxide (ATO) can inhibit glioma growth both in vitro and in vivo. While the use of ATO alone for solid tumor treatment sometimes was found to be ineffective which may be due to the protective pathways including heat shock proteins (HSPs) response induced by ATO. In this study, we modified HSPs expression to investigate whether HSPs had some effect on ATO induced glioma cell death. Trypan bule exclusion assay, mitochondrial membrane potential (MMP) Assay, and SubG1 detection were used to evaluate cell viability and western-blot was employed to detect HSPs and some apoptosis markers expression induced by ATO. Heat pre-treatment, HSPs inhibitor, or Heat Shock factor-1 (HSF1) knockdown by SiRNA was employed to modify HSPs levels. It was showed that KNK437 (HSPs inhibitor) or HSF1 knockdown significantly enhanced cell death, MMP disruption, JNK phosphorylation and caspase-3 cleavage induced by ATO, which was accompanied by abrogation of HSPs induction, while heat pre-treatment with clear HSPs induction had strong protection on the effects mentioned above. Those data suggested that HSPs play protective roles on ATO induced cell death in glioma. Inhibition of HSPs may have a synergistic effect with ATO on glioma treatment.

Testing the hormetic nature of homeopathic interventions through stress response pathways

The scientific foundations of hormesis are now well established and include various biochemical and molecular criteria for testing the hormetic nature of chemicals and other modulators. In order to claim homeopathy as being hormetic, it is essential that, in addition to the hormetic biphasic dose response, homeopathic remedies should fulfill one or more molecular criteria. Since stress response pathways, such as heat shock response, antioxidative response, autophagic response and unfolded protein response, are integral components of the physiological hormesis, it is important that homeopathic drugs be tested for these pathways if these are to be considered as hormetins and to cause hormesis.

Differential stress responses among newly received calves: variations in reductant capacity and Hsp gene expression

Bovine respiratory disease complex (BRD), a major economic concern to the beef cattle industry all over the world, is triggered by physical, biological and psychological stresses. It is becoming noticeable that the key to reducing BRD appears to be centered at reducing the response to stress. The aims of the present study were to detect individual variations in the stress response of newly received young calves through their leukocyte heat shock protein (Hsp) response, selected neutrophil-related gene expression and oxidative stress, and relate them to pulmonary adhesions at slaughter, an indicative sign of clinical and subclinical episodes of BRD at an early age. Differential expression patterns of Hsp60 and Hsp70A1A were revealed in newly received calves 1h, 5h and 1day after arrival, distinguishing between stress-responsive and non-stress-responsive individuals. Plasma cortisol was also indicative of stress-responsive and non-stress-responsive individuals, 1h and 5h after arrival. At the longer term, β-glycan levels were highest 7days after arrival and significantly correlated with an adhesion-free phenotype at slaughter. Oxidative stress responses, measured through the oxidation products of the exogenous linoleoyl tyrosine (LT) marker, revealed that hydroperoxidation and epoxidation of membranes may readily occur. Based on the LT oxidation products and levels of β-glycan, we present a discriminant analysis model, according to which vulnerable individuals may be predicted at near 100% probability 7days after arrival. Since clinical signs of BRD may often go undetected in feedlot calves, such a model, after its examination in large-scale experiments, may be a reliable tool for an early prediction of subclinical signs of BRD.

HSP70 response to aerobic training in aging human skeletal muscle

The response of heat shock proteins (HSP) to aerobic training has been investigated in animal models, but understudied in human skeletal muscle. Furthermore, very little is known regarding HSP in aging skeletal muscle. The purpose of this investigation was to determine basal mRNA and protein content of HSP70 before and after 12‐weeks of aerobic training on a cycle ergometer in nine elderly women (70±2y). Post training muscle biopsy samples were taken ~48 hours after the last exercise session in order to assess steady state levels of HSP70 mRNA and protein. Basal HSP70 mRNA was reduced (P<0.05) by 23±8% while HSP70 protein content was unchanged after aerobic training. The reductions in HSP70 mRNA may represent a reduction in age‐related basal stress after the training program. This investigation provides the first assessment of HSP70 regulation in aging human skeletal muscle with aerobic exercise training.Supported by NIH Grant AG032127

Heat shock proteins in some skin diseases

The family of heat shock protein (HSP) exists in all prokaryotic and eukaryotic cells. The expression increase of HSPs in response to environmental stress protects cells in a cenain degree. Most HSPs are molecular chaperones, and their principal function is to regulate protein metabolism. including protein folding, transmembrane transport, degradation and regulation of erroneous proteins. The expression of HSPs is closely related to epidermal differentiation, photoprotection and some skin diseases. This review focuses on the expression of HSPs in normal skin, photodamaged skin and lesions of some inflammatory skin diseases as well as its significance Key words: Skin diseases; Heat-shock proteins; Photobiology

Exercise training and experimental diabetes modulate heat shock protein response in brain

In diabetes, defense systems against cellular stress are impaired. Heat shock proteins (HSPs) function primarily as molecular chaperones. Factors that raise tissue HSP levels may slow progression of diabetes and improve diabetic complications that also affect brain tissue. This study tested the effect of an 8-week exercise training on brain HSP response in rats with or without streptozotocin-induced diabetes (SID). In untrained animals, the HSP levels were not different between SID and non-diabetic groups. Endurance training, however, increased HSP72 and HSP90 protein in non-diabetic rats, whereas SID significantly decreased the effect of training on these HSPs. At the mRNA level, HSP60, HSP90 and GRP75 were increased due to training, whereas HSP72 mRNA was only increased in exercise-trained diabetic animals. Training or diabetes had no effect on protein carbonyl content, a marker of oxidative damage. Altogether, our findings suggest that endurance training increases HSP expression in the brain, and that experimental diabetes is associated with an incomplete HSP response at the protein level.

Heat shock protein responses to eccentric weight or treadmill exercise in active young females

Previous studies have shown the increase of heat shock protein (HSP72) following exercise in animals. The purpose of this study was to examine the effect of type of exercise on HSP72 response in active young females. Nineteen female physical education students were randomly divided into two groups: an endurance training group (ETG) and a weight training group (WTG). The exercise protocol in the ETG included incremental running to exhaustion performed at 65–75% VO2max on a treadmill with a 0% grade. The subjects in the WTG also performed 4 sets of eccentric contractions of elbow flexors: two sets of 25 reps at 50% 1RM and two sets of 15–20 reps at 60% 1RM. Blood sampling from antecubital vein was done at baseline level (rest), mid-exercise and 30 min post-exercise in the same conditions, after a 12–14 h overnight fast. The samples were sent to a laboratory and centrifuged, and the serum used to analyse variables. A sandwich **Elisa and enzymatic assay were used for determination of HSP72 values and creatine kinase (CK) respectively. The data were analysed with repeated measures, LSD post hoc and independent t-test at p<0.05. The results showed HSP72 level alterations in mid- and post-tests were only significant in the ERG in comparison with baseline values (p=0.007, p=0.03 respectively). In addition, HSP72 level alterations within the ETG and WTG were only significant mid-test. Also CK levels insignificantly increased and decreased in the ETG and WTG respectively. The CK alterations in mid- and post-tests were insignificant between groups. Thus these results suggest that eccentric weight exercise induces a further increase in HSP72 levels.

Simulated diving after heat stress potentiates the induction of heat shock protein 70 and elevates glutathione in human endothelial cells

Heat stress prior to diving has been shown to confer protection against endothelial damage due to decompression sickness. Several lines of evidence indicate a relation between such protection and the heat shock protein (HSP)70 and HSP90 and the major cellular red-ox determinant, glutathione (GSH). The present study has used human endothelial cells as a model system to investigate how heat stress and simulated diving affect these central cellular defense molecules. The results demonstrated for the first time that a simulated dive at 2.6 MPa (26 bar) had a potentiating effect on the heat-induced expression of HSP70, increasing the HSP70 concentration on average 54 times above control level. In contrast, a simulated dive had no significant potentiating effect on the HSP90 level, which might be due to the higher baseline level of HSP90. Both 2 and 24-h dive had similar effects on the HSP70 and HSP90, suggesting that the observed effects were independent of duration of the dive. The rapid HSP response following a 2-h dive with a decompression time of 5 min might suggest that the effects were due to compression or pressure per se rather than decompression and may involve posttranslational processing of HSP. The exposure order seemed to be critical for the HSP70 response supporting the suggestion that the potentiating effect of dive was not due to de novo synthesis of HSP70. Neither heat shock nor a simulated dive had any significant effect on the intracellular GSH level while a heat shock and a subsequent dive increased the total GSH level approximately 62%. Neither of these conditions seemed to have any effect on the GSH red-ox status.

Heat shock transcription factors and sensory placode development

The heat shock transcription factor (HSF) family consists of at least three members in mammals and regulates expression of heat shock proteins in response to heat shock and proteotoxic stresses. Especially, HSF1 is indispensable for this response. Members of this family are also involved in development of some tissues such as the brain and reproductive organs. However, we did not know the molecular mechanisms that regulate developmental processes. Involvement of HSFs in the sensory development was implicated by the finding that human hereditary cataract is associated with mutations of the HSF4 gene. Analysis of gene-disrupted mice showed that HSF4 and HSF1 are required for the lens and the olfactory epithelium, respectively. Furthermore, a common molecular mechanism that regulates developmental processes was revealed by analyzing roles of HSFs in the two developmentally-related organs.

Stress inducible heat shock protein 70: a potent molecular and toxicological signature in arsenic exposed broiler chickens

This communication reports about heat shock protein response after arsenic exposure in broiler chickens in vivo and in vitro both. Splenocytes harvested in presence of sodium arsenite expressed Heat shock protein 70 (HSP 70) which could be identified on the basis of relative migration pattern and western blot analysis. Serum levels of HSP 70 in broiler chicken also increased after continuous feeding of sodium arsenite in drinking water. This particular observation may be attributed towards systematic inflammation, oxidative stress and hepatocellular injury. In vitro relative quantification of transcription level of HSP 70 revealed that splenocytes harvested in presence of sodium arsenite expressed (final concentration 3 and 7 μM/ml) more HSP 70 in comparison to cells harvested without sodium arsenite and the values were statistically significant (P < 0.001) when compared to untreated control. Collectively this result indicated that, HSP 70 level increased both in vivo and in vitro trials and may be used as potential molecular and toxicological biomarker.

The role of earthworms as biological indicators of soil contamination.

Earthworms are important components of the soil system. mainly because of their favorable effects on soil structure and function. In addition. earthworms help to increase soil fertility by formation of an organic matter layer in topsoil. These features. among others. have led to the popularity of earthworms as excellent biological indicators of soil pollution. Thus. earthworms are appropriate sentinel organisms to evaluate the impact of human activities to soil. The most widely studied earthworm species are Eisenia fetida. Eisenia andrei. Lumbricus terrestris and Lumbricus rubellus. Internationally standardized or academically not standardized test are described in the present article such as the nematode maturity index. the earthworm reproduction test. the lysosomal membrane stability test. immune system tests. enzymatic methods. heat-shock protein response assessment and DNA damage and alterations analyses

Proteome analysis of tobacco leaves under salt stress

The mechanisms responsible for the effects of salt stress on tobacco plants were examined by means of proteomic analysis. Tobacco plants were exposed to 0, 150, 250, 300, or 400 mM NaCl. At 150 mM NaCl or above, the plants showed a reduction in fresh weight and an increase in proline levels. Proteins extracted from the leaves of tobacco plants exposed to 150 mM NaCl were separated by 2-DE. Of 205 protein spots that were detected reproducibly in each gel, 18 were differentially expressed under NaCl treatment. Up-regulated proteins belonged to the photosynthesis category, whereas down-regulated proteins correspond to defense-related functions. Dose- and time-dependent studies showed that a stromal 70-kDa heat shock-related protein was markedly down-regulated by NaCl. Thus, down-regulation of the stromal 70-kDa heat shock protein in response to salt stress is likely the cause of failure to protect cells against salt stress of tobacco plants.

Increased Intracellular, Cell Surface, and Secreted Inducible Heat Shock Protein 70 Responses Are Triggered during the Monocyte to Dendritic Cell (DC) Transition by Cytokines Independently of Heat Stress and Infection and May Positively Regulate DC Growth

Physiologic triggers and functional consequences of endogenous heat shock protein (HSP) responses in dendritic cells (DC) are poorly defined. In this study, we show that even in the absence of heat stress and infection, a specific cohort of DC/proinflammatory cytokines (IL-4-IL-13/IL-6/GM-CSF) institutes an enhanced inducible (i)HSP70 intracellular and extracellular response in human monocyte-derived DC, especially during the monocyte to DC transition. Interestingly, whereas heat stress alone initiated an intracellular iHSP70 response in monocyte DC precursors, it did not promote cell surface or secreted iHSP70 responses, both of which were induced by cytokines independently of heat. The cytokine-induced iHSP70 response, which did not occur in lymphocytes, or monocytes-macrophages generated with M-CSF, was instituted within 48 h of cytokine exposure, and peaked upon commitment to DC growth at 72 h. Although a return to baseline levels was noted after this period, a distinct rise in iHSP70 occurred again during terminal DC maturation. Chemical inhibition of the iHSP70 response with either triptolide or KNK-437 was coupled with inhibition of DC differentiation and yielded cells displaying features of monocytes-macrophages. Exogenously supplied riHSP70 amplified events associated with cytokine-advanced DC differentiation/maturation, most notably the up-regulation of antiapoptotic proteins (Bcl-x(L)). Engaging the HSP receptor CD40 with CD40L produced identical results as extracellular riHSP70, and, moreover, an enhanced iHSP70 response. Thus, distinct iHSP70 and HSP receptor-mediated responses are triggered by cytokines irrespective of heat stress and infection in monocyte-derived DC and may function to positively regulate monocyte-derived DC, especially during critical periods of their growth.

Stress Type Dependence of Expression and Cytoplasmic-Nuclear Partitioning of Glucocorticoid Receptor, Hsp90 and Hsp70 in Wistar Rat Brain

Chronic exposure to stress is associated with different behavioral and neurological syndromes including impaired excitability of nerve cells in hippocampus (HIPPO) and prefrontal cortex (PFC), regions of the brain that are important for adaptation. The successful adaptation to stress involves negative feedback at the level of the hypothalamic-pituitary-adrenal (HPA) axis provided by the glucocorticoid receptor (GR), which is a steroid-dependent transcription factor found in a heterocomplex with heat shock proteins Hsp90 and Hsp70. In Wistar rats, chronic social isolation leads to a significant decrease in serum corticosterone (CORT), probably due to alterations in the GR signaling pathway. We exploited this type of stress, alone or in combination with acute immobilization, to define changes in the expression level and compartmental distribution of GR, Hsp90 and Hsp70 in HIPPO and PFC. The results indicated that in acute and combined stress, when CORT was increased, GR was translocated to the nucleus in both brain structures. Under chronic stress, when CORT was below the control level, GR was retained in the cytoplasm of PFC, and evenly distributed between compartments in HIPPO. Simultaneously, heat shock proteins partitioning in HIPPO seemed to be mainly stress type-independent, while that of PFC was dependent on stress type. Thus, the stress type-specific responses of GR and heat shock proteins were mainly detected in PFC rather than in HIPPO of Wistar rats. The observed alterations in protein expression and cytoplasmic-nuclear partitioning of the GR, Hsp90 and Hsp70 proteins may be related to maladaptive response of the HPA axis under chronic stress.

Heat shock protein translocation and expression response is attenuated in response to repeated eccentric exercise

This study hypothesized that heat shock protein (HSP) translocation and upregulation is more probable to occur after eccentric exercise than after concentric exercise or repeated eccentric exercise. Fourteen young, healthy, untrained male subjects completed two bench-stepping exercise bouts with 8 weeks between bouts, and were compared with a control group (n = 6). Muscle biopsies collected from m. vastus lateralis of both legs prior to and at 3 h, 24 h and 7 days after exercise were quantified for mRNA levels and/or for HSP27, alphabeta-crystallin and inducible HSP70 content in cytosolic and cytoskeletal protein fractions. The first bout of exercise reduced muscle strength and increased muscle soreness predominantly in the eccentric leg (P < 0.05). These responses were attenuated after the repeated eccentric exercise bout (P < 0.05), suggesting a repeated bout adaptation. Increases in inducible HSP70 and HSP27 protein content in cytoskeletal fractions were observed exclusively after eccentric exercise (P < 0.05). For HSP27, an approx. 10-fold upregulation after first-bout eccentric exercise was attenuated to a an approximately fourfold upregulation after the repeated eccentric exercise bout. mRNA levels for HSP70, HSP27 and alphabeta-crystallin were upregulated within approximately two to fourfold ranges at time points 3 and 24 h post-exercise (P < 0.05). This upregulation was induced exclusively by eccentric exercise but with a tendency to attenuated expression 3 h after the repeated eccentric exercise bout. Our results show that HSP translocation and expression responses are induced by muscle damaging exercise, and suggest that such HSP responses are closely related to the extent of muscle damage.