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PubMed1995

Heat shock proteins and molecular chaperones: implications for adaptive responses in the skin.

Recent advances in the biology of heat-shock proteins (hsps) are reviewed. These abundant and evolutionarily highly conserved proteins (also called stress proteins) act as molecular escorts. Hsps bind to other cellular proteins, help them to fold into their correct secondary structures, and prevent misfolding and aggregation during stress. Cytoplasmic hsp70 and hsp60 participate in complicated protein-folding pathways during the synthesis of new polypeptides. Close relatives of hsp70 and hsp60 assist in the transport and assembly of proteins inside intracellular organelles. Hsp90 may have a unique role, binding to the glucocorticoid receptor in a manner essential for proper steroid hormone action. Hsps may also be essential for thermotolerance and for prevention and repair of damage caused by ultraviolet B light. A unique class of T lymphocytes, the gamma delta T cells, exhibits a restricted specificity against hsps. These T cells may constitute a general, nonspecific immune mechanism directed against the hsps within invading organisms or against very similar hsps within invading organisms or against very similar hsps expressed by infected (stressed) keratinocytes. Immunologic cross-reactivity between hsps of foreign organisms and of the host may play a role in some autoimmune diseases. Although hsps are expressed in the skin, many questions remain about their role during injury, infection, and other types of cutaneous pathophysiology.

Adaptation, Physiological↗

PubMed2003

Oral microbial heat-shock proteins and their potential contributions to infections.

The oral cavity is a complex ecosystem in which several hundred microbial species normally cohabit harmoniously. However, under certain special conditions, the growth of some micro-organisms with a pathogenic potential is promoted, leading to infections such as dental caries, periodontal disease, and stomatitis. The physiology and pathogenic properties of micro-organisms are influenced by modifications in environmental conditions that lead to the synthesis of specific proteins known as the heat-shock proteins (HSPs). HSPs are families of highly conserved proteins whose main role is to allow micro-organisms to survive under stress conditions. HSPs act as molecular chaperones in the assembly and folding of proteins, and as proteases when damaged or toxic proteins have to be degraded. Several pathological functions have been associated with these proteins. Many HSPs of oral micro-organisms, particularly periodontopathogens, have been identified, and some of their properties-including location, cytotoxicity, and amino acid sequence homology with other HSPs-have been reported. Since these proteins are immunodominant antigens in many human pathogens, studies have recently focused on the potential contributions of HSPs to oral diseases. The cytotoxicity of some bacterial HSPs may contribute to tissue destruction, whereas the presence of common epitopes in host proteins and microbial HSPs may lead to autoimmune responses. Here, we review the current knowledge regarding HSPs produced by oral micro-organisms and discuss their possible contributions to the pathogenesis of oral infections.

Adaptation, Physiological↗

PubMed2006

Heat shock of cultivated and wild wheats during early seedling stage: growth, cell viability and heat shock proteins.

Growth, cell viability and heat shock proteins (HSPs) in Bezostaya-1, Cukurova-86 and Diyarbakir-81 cultivated wheat cultivars and three Aegilops species were investigated. Etiolated seedlings were exposed to 23 degrees C, 32 degrees C, 35 degrees C, 37 degrees C and 38 degrees C for 24 h, and 35 degrees C (24 h) --> 50 degrees C (1 h) and 37 degrees C (24 h) --> (50 degrees C (1 h). At the end of recovery growth periods, the shoot lengths of the genotypes generally decreased significantly at 35, 37 and 38 degrees C. The acquired thermal tolerance (ATT) in intact seedlings was over 50% at 35 degrees C --> 50 degrees C and 37 degrees C --> 50 degrees C, but in cell viability test it ranged from 2.75% (Ae. triuncialis) to 32.87 (Bezostaya-1) at 35 degrees C, and from 2.82% (Ae. triuncialis) to 37.82 (Bezostaya-1) at 37 degrees C. Ae. triuncialis was most sensitive genotype in both ATT determination. In electrophoretic profiles of proteins, while some HSPs were newly synthesized, some normal cellular proteins disappeared at 37 degrees C and 37 degrees C -->50 degrees C compared to 23 degrees C. The number of low molecular weight (LMW) HSPs were more than intermediate- (IMW) and high- (HMW) HSPs. The genotypes had both common (12 HSPs between at least two genotypes) and genotype-specific (33 HSPs) LMW HSPs. The common HSP of 19.8 kDa (pI 6.5) was synthesized in Bezostaya-1, Cukurova-86, Diyarbakir-81, Ae. biuncialis and Ae. umbellulata. Bezostaya-1 is the only genotype that synthesized 12 IMW and 2 HMW HSPs at 37 degrees C --> 50 degrees C. Ae. triuncialis had only two common LMW HSPs [22.1 (pI 7.1) and 24.2 kDa (pI 6.5)].

Cell Survival↗

PubMed1993

Heat shock in human neutrophils: superoxide generation is inhibited by a mechanism distinct from heat-denaturation of NADPH oxidase and is protected by heat shock proteins in thermotolerant cells.

Independently of the stimulating agent used, generation of O2- by human neutrophils is transiently inhibited when the cells have been exposed to elevated temperatures. This phenomenon is concomitant with the synthesis of heat shock proteins (HSPs). We have investigated a possible relationship between HSPs and modulation of NADPH oxidase activity in human neutrophils exposed to heat. HSPs were not involved in the inhibition of O2- generation since 1) in enucleated cytoplasts, which are unable to synthesize proteins, the generation of O2- was inhibited after exposure to 43 degrees C, 2) using actinomycin D (Act D) in intact cells, it was possible selectively to inhibit the synthesis of HSPs without modifying the inhibition of NADPH oxidase activity that followed HS. Furthermore, the recovery of NADPH oxidase activity was not under the control of HSPs because the enzyme recovered as well in Act D-treated neutrophils. The NADPH oxidase activity was reconstituted in a cell-free assay by combining the cytosol with the plasma membrane-enriched fraction in the presence of arachidonic acid (AA) and NADPH. Subcellular fractions obtained from control or heated neutrophils exhibited similar oxidase activities suggesting that heat exposure did not induce denaturation of the oxidase components but rather altered the mechanisms of translocation and/or assembly of these components with the plasma membrane. This hypothesis was supported by the inhibition of the granule release in heated cells, a process which also requires translocation and association fusion with the plasma membrane. On the other hand, preexposure of neutrophils to HS prevented the inhibition of O2- generation during a second challenging HS. This acquired thermotolerance was abolished when the synthesis of HSPs was inhibited during the first HS with Act D, indicating a direct relationship between protection of O2- generation and synthesis of HSP. Here we demonstrate that synthesis of HSPs and inhibition or recovery of NADPH oxidase activity are concomitant but unrelated phenomena. In contrast, accumulation of HSPs in thermotolerant neutrophils appeared to play an important role in the prevention of NADPH oxidase inhibition. These results provide further insights into the behavior of human neutrophils and NADPH oxidase upon heat injury.

Cell Degranulation↗

PubMed2007

Plasminogen and angiostatin interact with heat shock proteins.

Previous studies from this laboratory have demonstrated that plasminogen and angiostatin bind to endothelial cell (EC) surface-associated actin via their kringles in a specific manner. Heat shock proteins (hsps) like hsp 27 are constitutively expressed by vascular ECs and regulate actin polymerization, cell growth, and migration. Since many hsps have also been found to be highly abundant on cell surfaces and there is evidence that bacterial surface hsps may interact with human plasminogen, the purpose of this study was to determine whether human plasminogen and angiostatin would interact with human hsps. ELISAs were developed in our laboratory to assess these interactions. It was observed that plasminogen bound to hsps 27, 60, and 70. In all cases, binding was inhibited (85-90%) by excess (50 mM) lysine indicating kringle involvement. Angiostatin predominantly bound to hsp 27 and to hsp 70 in a concentration- and kringle-dependent manner. As observed previously for actin, there was concentration-dependent inhibition of angiostatin's interaction with hsp 27 by plasminogen. In addition, 30-fold molar excess actin inhibited (up to 50%), the interaction of plasminogen with all hsps. However, 30-fold molar excess actin could only inhibit the interaction of angiostatin with hsp 27 by 15-20%. Collectively, these data indicate that (i) while plasminogen interacts specifically with hsp 27, 60, and 70, angiostatin interacts predominantly with hsp 27 and to some extent with hsp 70; (ii) plasminogen only partially displaces angiostatin's binding to hsp 27 and (iii) actin only partially displaces plasminogen/angiostatin binding to hsps. It is conceivable therefore that surface-associated hsps could mediate the binding of these ligands to cells like ECs.

Actins↗

PubMed1992

Slow positive dorsal cord potentials activated by heterosegmental stimuli.

Heterosegmental slow positive waves (HSPs) and segmental spinal cord potentials were recorded from the cord dorsum in ketamine-anesthetized rats. Forepaw stimulation produced HSPs in the lumbo-sacral enlargement (lumbar HSPs), whereas hind paw stimulation evoked HSPs in the cervical cord (cervical HSP). Both the HSP and the secondary component of the slow positive wave (P2s) in the segmental spinal cord potential were highly vulnerable to anesthetics and completely disappeared after spinal cord transection at the C1/2 level, indicating that both the HSP and P2s are produced by a long feedback loop via supraspinal structures. The lumbar HSP evoked by forepaw stimulation was maximal in amplitude at the L5 level and more dominant in the ipsilateral cord dorsum than in the contralateral one, but widely distributed in the lumbo-sacral cord. A variability of onset (7-18 msec for cervical and 5-17 msec for lumbar HSPs) and peak (22-35 msec for cervical and 12-50 msec for lumbar HSPs) suggests the existence of several nuclei to form the feedback loops for descending impulses to produce the HSPs. There were no peak latency differences between the HSPs and P2s. Since there were several similar characteristics between the P2s and HSP such as a high vulnerability to anesthetic, a complete disappearance after high spinal transection and similar response curves to graded intensities of stimulation, there may be a close relationship between their feedback nuclei and the pathways mediating them. All wide dynamic range (WDR) neurons (12/12) in lamina V of Rexed responded to heterosegmental stimulation with inhibition of firing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2005

Enhanced expression of heat shock proteins in gradually dying cells and their release from necrotically dead cells.

Heat shock proteins (HSPs) have molecular chaperone functions in protein biogenesis as well as cytoprotective functions against deleterious environmental stresses, and they work mainly inside of the cells. HSPs are usually induced in living cells that have been exposed to mild stresses or have recovered from severe stresses. Here, we show the enhanced synthesis of HSPs in gradually and necrotically dying cells that were treated with a high concentration of acrylamide (10 mM). This treatment caused irreversible cell death. The synthesis of HSPs, which was enhanced before cell death, was mediated by the activation of heat shock transcription factor 1 (HSF1); that is, the treatment led to the phosphorylation of HSF1, formation of characteristic HSF1 granules in the nucleus, and acquisition of DNA binding ability of HSF1. The induction of HSPs by acrylamide treatment was dependent on the consensus sequence of heat shock element (HSE) as demonstrated by a reporter assay. Also, several HSPs (Hsp90, Hsc70, Hsp70, Hsp60, Hsp47, Hsp40, and Hsp27) were detected outside of the cells after the treatment with acrylamide, indicating that these HSPs are released from necrotically dead cells. These results suggest that when cells are slowly and irreversibly dying, they augment the expression of HSPs and release them outside of the cells as a danger signal or dying messages.

Acrylamide↗

PubMed2004

Autoimmunity to heat shock proteins in atherosclerosis.

Current evidence lends increasing support to immunoinflammatory mechanisms as one of the prime pathogenic processes involved in the development and progression of atherosclerosis. It has been observed that most human beings have cellular and humoral reactions against microbial heat shock protein (HSP). Autoantibody levels against HSPs are significantly increased in patients with atherosclerosis and T lymphocytes specifically responding to HSPs have been demonstrated within atherosclerotic plaques. Most of the known risk factors for atherosclerosis, viz. oxidized low-density lipoprotein, hypertension, infections and oxidative stress, evoke increased expression of HSPs in endothelial cells, smooth muscle cells and macrophages, the main cellular constituents of atherosclerotic plaques. Evolutionary conservation has resulted in a high degree of sequence homology between microbial and human HSPs and hence the immune reactions against microbial HSPs carry a risk of being misdirected towards human HSPs expressed in the stressed cells of the blood vessels. HSPs and anti-HSP antibodies have been shown to elicit production of pro-inflammatory cytokines by macrophages and adhesion molecules by endothelial cells in various in vitro and animal model studies. These autoimmune reactions to HSPs expressed in the vascular tissue can contribute to both initiation and perpetuation of atherosclerosis.

Animals↗

PubMed1997

Hair cycle-dependent expression of heat shock proteins in hair follicle epithelium.

BACKGROUND: Heat shock proteins (HSPs) have a physiologic function in unstressed cells, which is believed to include a role as a "molecular chaperone." The hair cycle is characterized by rhythmic tissue remodelling processes, and is an intriguing model for studying the relation between keratinocyte differentiation and HSP expression under physiologic circumstances. We have therefore studied, by immunofluorescence, the expression of selected HSPs during the murine hair cycle. METHODS: The association between hair follicle cycling and the expression of three selected HSPs (HSPs 27, 60, and 72) was examined by immunofluorescence, using the depilation-induced hair cycle of C57BL/6 mice. RESULTS: HSP expression was absent from telogen follicles, and was restricted predominantly to keratinocytes in the bulge and the cycling epithelial portion of the hair follicle during anagen and catagen. Immunoreactivity for HSPs 27, 60, and 72 in the hair bulb increased significantly during anagen VI and the catagen transformation of the follicle, and decreased again abruptly with completion of the catagen-telogen transformation. The expression pattern of HSPs 60 and 72 in situ was cytoplasmic, whereas that of HSP 27 was both cytoplasmic and nuclear. CONCLUSIONS: These observations suggest that the synthesis of HSPs by hair bulb keratinocytes is related to the anagen-catagen transformation of the follicle, possibly reflecting keratinocyte apoptosis and/or terminal differentiation in the regressing, cycling portion of the follicle. In addition, the rather proximal localization of HSP expression makes it unlikely that the HSPs examined interact with the more distally located intrafollicular gamma/delta T-cell receptor-positive lymphocytes.

Animals↗

PubMed2005

Heat shock proteins and acute leukemias.

Heat shock proteins (HSPs) acts as molecular chaperones by helping in the refolding of misfolded proteins and assisting in their elimination if they become irreversibly damaged. HSPs induced by stress treatment have a role in the modulation of apoptosis. The reduction in protein expression levels was correlated with an increased susceptibility to drug-induced apoptosis. HSPs have also been implicated in the resistance of leukemia cells to potential therapeutic agents. The mechanisms of cellular protection used by HSPs have yet to be fully defined. HSPs were shown highly expressed by acute myeloid leukemia (AML) cells as well as by acute lymphoblastic leukemia (ALL) cells. HSP expressions were correlated with that of differentiation antigens and that of drug-resistance and apoptosis proteins. Complete remission (CR) rates were higher in patients with lower expression of HSPs. Overall survival (OS) was significantly longer in patients with lower expression of HSPs. Therapeutically, inhibition of inducible HSP expression or activity should not cause any undesired side effects. HSPs emerge as novel therapeutic targets in anticancer protocols. Early results of phase I studies indicate that 17-allylamino-17-demethoxygeldamycin (17-AAG), capable of binding and disrupting the function of HSP90, results in an acceptable toxicity profile while achieving in vivo disruption of multiple oncogenic client proteins.

Animals↗

PubMed1984

Acquisition of Thermotolerance in Soybean Seedlings : Synthesis and Accumulation of Heat Shock Proteins and their Cellular Localization.

When soybean Glycine max var Wayne seedlings are shifted from a normal growth temperature of 28 degrees C up to 40 degrees C (heat shock or HS), there is a dramatic change in protein synthesis. A new set of proteins known as heat shock proteins (HSPs) is produced and normal protein synthesis is greatly reduced. A brief 10-minute exposure to 45 degrees C followed by incubation at 28 degrees C also results in the synthesis of HSPs. Prolonged incubation (e.g. 1-2 hours) at 45 degrees C results in greatly impaired protein synthesis and seedling death. However, a pretreatment at 40 degrees C or a brief (10-minute) pulse treatment at 45 degrees C followed by a 28 degrees C incubation provide protection (thermal tolerance) to a subsequent exposure at 45 degrees C. Maximum thermoprotection is achieved by a 2-hour 40 degrees C pretreatment or after 2 hours at 28 degrees C with a prior 10-minute 45 degrees C exposure. Arsenite treatment (50 micromolar for 3 hours) also induces the synthesis of HSP-like proteins, and also provides thermoprotection to a 45 degrees C HS; thus, there is a strong positive correlation between the accumulation of HSPs and the acquisition of thermal tolerance under a range of conditions.During 40 degrees C HS, some HSPs become localized and stably associated with purified organelle fractions (e.g. nuclei, mitochondria, and ribosomes) while others do not. A chase at 28 degrees C results in the gradual loss over a 4-hour period of the HSPs from the organelle fractions, but the HSPs remain selectively localized during a 40 degrees C chase period. If the seedlings are subjected to a second HS after a 28 degrees C chase, the HSPs rapidly (complete within 15 minute) relocalize in the organelle fractions. The relative amount of the HSPs which relocalize during a second HS increases with higher temperatures from 40 degrees C to 45 degrees C. Proteins induced by arsenite treatment are not selectively localized with organelle fractions at 28 degrees C but become organelle-associated during a subsequent HS at 40 degrees C.

Journal Article↗

PubMed1990

Heat Shock Proteins and Their mRNAs in Dry and Early Imbibing Embryos of Wheat.

Two-dimensional gels of in vitro translation products of mRNAs isolated from quiescent wheat (Triticum aestivum) embryos demonstrate the presence of mRNAs encoding heat shock proteins (hsps). There were no detectable differences in the mRNAs found in mature embryos from field grown, from 25 degrees C growth chamber cultivated, or from plants given 38 degrees C heat stresses at different stages of seed development. The mRNAs encoding several developmentally dependent (dd) hsps were among those found in the dry embryos. Stained two-dimensional gels of proteins extracted from 25 degrees C growth chamber cultivated wheat embryos demonstrated the presence of hsps, including dd hsps. A study of the relationship of preexisting hsp mRNAs and the heat shock response during early imbibition was undertaken. Heat shocks (42 degrees C, 90 minutes) were administered following 1.5, 16, and 24 hours of 25 degrees C imbibition. While the mRNAs encoding the low molecular weight hsps decayed rapidly upon imbibition, the mRNAs for dd hsps persisted longer and were still detectable following 16 hours of imbibition. After 1.5 hours of imbibition, the mRNAs for the dd hsps did not accumulate in response to heat shock, even though the synthesis of the proteins was enhanced. Thus, an applied heat shock appeared to lead to the preferential translation of preexisting dd hsp mRNAs. The mRNAs for the other hsps, except hsp 70, were newly transcribed at all of the imbibition times examined. The behavior of the hsp 70 group of proteins during early imbibition was examined by RNA gel blot analysis. The mRNAs for the hsp 70 group were detectable at moderate levels in the quiescent embryo. The relative level of hsp 70 mRNA increased after the onset of imbibition at 25 degrees C and remained high through 25.5 hours of prior imbibition. The maximal levels of these mRNAs at 25 degrees C was reached at 17.5 hours of imbibition. Heat shock caused modest additional accumulation of hsp70 mRNA at later imbibition times.

Journal Article↗

PubMed1990

Synthesis of a select group of proteins by Neisseria gonorrhoeae in response to thermal stress.

We report the thermal conditions that induce the heat shock response in Neisseria gonorrhoeae. Under conditions of thermal stress, Neisseria gonorrhoeae synthesizes heat shock proteins (hsps), which differ quantitatively from conventionally studied gonococcal proteins. Gonococci accelerate the rate of synthesis of the hsps as early as 5 min after the appropriate stimulus is applied, with synthesis continuing for 30 min, as demonstrated by in vivo labeling experiments with L-[35S]methionine. Two of the gonococcal hsps are immunologically cross-reactive with the hsps of Escherichia coli, DnaK and GroEL, as demonstrated by Western blot (immunoblot) analysis. Ten hsps can be identified on two-dimensional autoradiograms of whole gonococci (total protein). Four hsps can be identified on two-dimensional autoradiograms of 1% N-lauroylsarcosine (sodium salt) (Sarkosyl)-insoluble membrane fractions. Two of the hsps from the 1% Sarkosyl-insoluble fraction are found exclusively in this fraction, suggesting that they are membrane proteins. The identification of this group of proteins will facilitate further study of the function of these proteins and provide insight into the possible role of hsps in disease pathogenesis.

Animals↗

PubMed1994

Heat shock response and heat shock protein antigens of Vibrio cholerae.

Sixteen heat shock proteins (Hsps) have been identified in the hypertoxinogenic strain 569B of Vibrio cholerae which are synthesized in response to small and large elevations of temperature. The induction of the Hsps is necessary for the cells to survive the deleterious effects of heat. There is no difference in the pattern of induction of the Hsps in V. cholerae strains varying in levels of toxinogenicity. One of the major low-molecular-mass Hsps, a 16-kDa protein, is preferentially degraded following shift down of temperature. This protein is induced at a much lower level at high temperatures in cells maintained in the laboratory for a prolonged period. The only Hsp located in the outer membrane of V. cholerae cells is a 23-kDa protein. Western immunoblot analysis with human immune sera collected from convalescent cholera patients revealed that this protein is markedly immunogenic. The human immune serum also reacted with the 69- and 16-kDa major Hsps and the 88-, 66-, and 46-kDa Hsps but not with the 61-kDa major Hsp identified as the groEL gene product. All major Hsps reacted with rabbit anti-V. cholerae sera. Ethanol stress leads to the induction of four of the major Hsps and three additional proteins.

Adaptation, Biological↗

PubMed1989

Factors influencing the heat shock response of Xenopus laevis embryos.

We have further characterized the heat shock response of Xenopus laevis embryos. Xenopus embryos respond to heat shock by consistently synthesizing four major heat shock proteins (hsps) of 62, 70, 76, and 87 kilodaltons. In addition to these hsps, heat-shocked embryos also exhibit the synthesis of several minor hsps. The synthesis of these hsps is often variable. We have monitored the effects of different temperatures and lengths of heat shock on the pattern and intensity of hsp synthesis. In general, the four major hsps are induced more strongly at higher temperatures and during increasing intervals of heat shock. The temperature and duration of heat shock can affect the synthesis of the minor hsps, however. Some hsps are synthesized at lower temperatures only (i.e., below 37 degrees C), whereas others are synthesized only at higher temperatures (i.e., above 37 degrees C). We have extensively examined the characteristics of hsp 35 synthesis, one of the most variably synthesized hsps. This hsp is characteristically synthesized at temperatures above 35 degrees C and usually during the first 40 min of heat shock, after which it becomes undetectable. In some experiments, its synthesis is restimulated during later intervals of heat shock. Hsp 35 is also under developmental regulation. It is not synthesized by heat-shocked embryos until the late blastula to early gastrula stage. After this brief period of inducibility, its synthesis is dramatically reduced in mid- to late gastrulae, but reappears in heat-shocked neurulae. We have previously demonstrated that hsp 35 is related to the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The induction of hsp 35 synthesis is inversely correlated with the constitutive levels of GAPDH specific activity. In this paper we document further correlations between the synthesis of hsp 35 and GAPDH specific activity during early Xenopus development.

Animals↗

PubMed2000

Molecular chaperones in the kidney: distribution, putative roles, and regulation.

Molecular chaperones are intracellular proteins that prevent inappropriate intra- and intermolecular interactions of polypetide chains. A specific group of highly conserved molecular chaperones are the heat shock proteins (HSPs), many of which are constitutively expressed but most of which are inducible by diverse (in some cases specific) stress factors. HSPs, either alone or in cooperation with "partner" chaperones, are involved in cellular processes as disparate as correct folding and assembly of proteins, transport of proteins to specific intracellular locations, protein degradation, and preservation and restructuring of the cytoskeleton. The characteristic distribution of individual HSPs in the kidney, and their response to different challenges, suggests that a number of HSPs may fulfill specific, kidney-related functions. HSP72 and the osmotic stress protein 94 (Osp94) appear to participate in the adaptation of medullary cells to high extracellular salt and urea concentrations; the small HSPs (HSP25/27 and crystallins) may be involved in the function of mesangial cells and podocytes and contribute to the volume-regulatory remodeling of the cytoskeleton in medullary cells during changes in extracellular tonicity. HSP90 contributes critically to the maturation of steroid hormone receptors and may thus be a critical determinant of the aldosterone sensitivity of specific renal epithelial cells. Certain HSPs are also induced in various pathological states of the kidney. The observation that the expression of individual HSPs in specific kidney diseases often displays characteristic time courses and intrarenal distribution patterns supports the idea that HSPs are involved in the recovery but possibly also in the initiation and/or maintenance phases of these disturbances.

Animals↗

PubMed2003

Heat shock protein expression in the eye and in uveal melanoma.

PURPOSE: Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types, whereas HSPs may also have clinical use as stimulators in tumor vaccination. HSP expression levels were determined in normal eyes and in uveal melanoma and tested whether HSPs expression was associated with prognostic parameters in the uveal melanoma. METHODS: Expression of HSP27, HSP70, HSP90, and glycoprotein96 (GP96) were determined on paraffin-embedded and frozen sections from seven healthy eyes, 20 primary uveal melanomas without prior treatment, and 18 uveal melanomas after prior treatment. HSP expression was determined by alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemistry, using appropriate monoclonal antibodies and scored semiquantitatively. Expression of HSPs was validated on retinal tissue of a normal eye and in two uveal melanoma cell lines by Western blot analysis. RESULTS: Expression of HSPs was observed in epithelial and pigment cells of the normal eyes. In uveal melanoma, the level of expression of HSPs varied. Expression of HSP27 and GP96 was noted in more than 30 of 38 uveal melanomas (with, respectively, a mean of 66% and 53% positive cells). HSP70 and HSP90 were expressed in 6% of tumor cells. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors. There was not a significant difference in expression of the HSPs between uveal melanomas with or without any type of prior treatment. CONCLUSIONS: In this study, expression of HSPs in uveal melanoma is not correlated with known histopathologic prognostic factors. The high expression of GP96 indicates that this protein is a potential vector in tumor vaccination in patients with large uveal melanomas.

Adult↗

PubMed2006

Antibodies against heat shock proteins in environmental stresses and diseases: friend or foe?

Heat shock proteins (Hsps) can be found in two forms, intracellular and extracellular. The intracellular Hsps are induced as a result of stress and have been found to be cytoprotective in many instances due to their chaperone functions in protein folding and in protein degradation. The origin and role of extracellular Hsps is less clear. Although they were suspected originally to be released from damaged cells (necrosis), their presence in most normal individuals rather suggests that they have regulatory functions in circulation. As immunodominant molecules, Hsps can stimulate the immune system, leading to the production of autoantibodies recognizing epitopes shared by microbial and human Hsps. Thus, extracellular Hsps can influence the inflammatory response as evidenced by the production of inflammatory cytokines. Antibodies to Hsps have been found under normal conditions but seem to be increased in certain stresses and diseases. Such antibodies could regulate the inflammatory response positively or negatively. Here, we review the literature on the findings of antibodies to Hsps in situations of environmental or occupational stress and in a number of diseases and discuss their possible significance for the diagnosis, prognosis, or pathogenesis of these diseases.

Antibodies↗