70-kD Heat Shock Research Articles

Folliculocentric Herpes: A Clinicopathological Study of 28 Patients.

The cutaneous manifestations of herpes infection are primarily in the context of active infection and of the post-herpetic zosteriform eruption. The former manifests cytopathic alterations diagnostic of herpes. The latter includes lichen planus-like and granuloma annulare-like eruptions and lymphocytoma cutis. We encountered skin biopsies from 28 patients whose acute or chronic herpetic or post-herpetic zosteriform lesions manifested folliculocentricity. The clinical appearance of the lesions was correlated with the histopathologic and immunohistochemical features of paraffin-embedded skin biopsies to determine the specific viral etiology. A history of underlying medical disease was noted if present. There were 16 men and 12 women with a folliculocentric eruption occurring after a known herpetic eruption or manifesting cytopathic changes and/or immunohistochemical findings compatible with herpes virus in lesional skin biopsies. Underlying immune dysregulatory states were present in most cases, namely, malignancy, anticonvulsant or antidepressant therapy, diabetes mellitus, psoriasis, Crohn disease, and other conditions. All biopsies demonstrated dense lymphohistiocytic infiltrates in or around hair follicles with variable necrosis, while active infections also showed cytopathic and/or immunohistochemical evidence of herpetic alterations, most commonly varicella zoster. Other features included interfollicular interface dermatitis, lymphocytic eccrine hidradenitis, neuritis, and folliculocentric vasculitis. Cutaneous herpetic eruptions can evoke a predominantly folliculocentric mononuclear cell reaction and vasculitis; there is an association with underlying endogenous and/or iatrogenic immune dysregulation. Most cases are secondary to reactivation of varicella zoster. The histomorphology suggests a role for cell-mediated immunity. Antigenic homology of an endogenous 72-kd heat shock protein in follicles with that of a herpetic heat shock protein, in concert with an intrafollicular proliferative response of γ-δ T lymphocytes, may explain the follicular localization and composition of the infiltrate.

Induction in vitro of 72-kD heat shock protein in a continuous culture of rat thyroid cells, FRTL5.

In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been heated at 42.5 degrees C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retrocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.

Epithelial cells and adipose cells both have their own temporal profile in 72-kd heat-shock protein expression determining their tolerance for ischaemia

Seventy-two-kd heat-shock protein (HSP72) is one of the stress markers induced in cells under stress, such as in the case of ischaemia. Recent studies have suggested that HSP72 is a 'molecular chaperone' to protect cells from various kinds of stress, and that the temporal profile of HSP72 induction is related to ischaemic vulnerability. In this study, we attempted to analyse the temporal profiles of HSP72 induction in epithelial and adipose cells in skin flaps after various periods of transient ischaemia, and we investigated the reason why there were differences in ischaemic tolerance between these cells. We used the abdominal skin flap of Wister rats, which were divided into three groups: the sham control group (n=27), the 2-h ischaemia group (n=25), and the 8-h ischaemia group (n=25). At periods of 8, 24, 48, 96 h, and 7 days after reperfusion, we examined them for any histological changes and performed immunostaining for HSP72 (n=5, each time point). Two animals in the sham control group were sacrificed to harvest the samples immediately after the skin flaps were elevated. As a result, the epithelial cells in all groups revealed positive for HSP72 through the time course, regardless of the ischaemic stresses, and they were alive at 7 days. In the adipose cells, the cells in the sham control group revealed no immunoreactivity after the reperfusion, and they had no change at 7 days. In the 2-h ischaemia group, the adipose cells gradually increased the reactivity for HSP72; consequently they survived beyond 7 days. In the 8-h ischaemia group, the reactivity for HSP72 gradually decreased; consequently they played out a delayed cell death at 7 days. We concluded that these differences of HSP72 expression were related to the cellular vulnerability to ischaemia.

Upregulation of HSP-72 in a Human Renal Allograft during Reflow

Many types of renal injury, which are of potential relevance in transplantation medicine (such as extreme temperatures, ischemia, cytotoxic agents and cyclosporine), are known to induce the cellular stress response. Recently, we reported the first data on the 72-kD heat shock protein (HSP-72), a key player of the mammalian stress response, in a large number of nonperfused human donor kidneys (1). HSP-72 expression at both protein and mRNA levels remained low in the allografts at the time of engraftment regardless of pretransplant insults and posttransplant outcome. These data disqualified HSP-72 as a marker for allograft outcome in the clinical setting and suggested that constitutive HSP-72 expression does not play a role in graft protection. Herein, we report the findings on HSP-72 expression in a 10.5-year-old boy whose renal allograft was biopsied during early posttransplant reperfusion. His primary disease was chronic glomerulonephritis; the transplantation was performed after 12 months of peritoneal dialysis. The 52-year-old donor had died because of a cerebral insult. The creatinine at the time of explantation was 0.6 mg/dl, the donor was on low doses of pressors, cold ischemic time was 16 hours, and the mismatch was 2-2-0. The immunosuppressive regimen consisted of cyclosporine A, steroids, and mycophenolate mofetil. A routine donor kidney biopsy was performed immediately before engraftment, and a clinically indicated repeat biopsy was performed at 18 hours thereafter because of unexplained primary nonfunction. Immunohistochemical analysis of HSP-72 expression before and after engraftment is shown in Fig. 1.FIGURE 1.: HSP-72 expression in pre-transplant biopsy (upper panel) versus early re-perfusion (lower panel).Pretransplant biopsy demonstrated only weak and focal HSP-72 expression among different tubular segments (and thus failed to predict the complicated course). In strict contrast, the allograft biopsy during early reperfusion exhibited obvious overexpression of HSP-72 and thus suggested HSP-mediated cellular processes severe enough to produce a relevant in vivo stress response in the renal allograft. HSP-72 expression in the nonperfused donor kidney might have been insufficiently induced until the engraftment, and/or might have been prevented or even degraded during cold storage, despite significant expression at the time of harvest (2). At present, material from nonperfused organs constitutes the basis for most studies on posttransplant risk assessment. Data like ours should fuel discussions on strategies of early posttransplant biopsy procurement to improve clinical applicability of biomarkers. More importantly, this case provides the first direct evidence for the involvement of HSP-72 mediated cellular repair mechanisms in human renal allografts during reperfusion. These data corroborate a broad body of experimental evidence and support the potential of HSP-72 as a cytoprotective tool (3). Based on the recent finding of low pretransplant HSP-72 expression in the majority of donor kidneys, therapeutic interventions such as specific ex-vivo treatment of organs during cold storage fostering overexpression (and/or preventing degradation) of HSP-72 can be considered as an attractive concept in human transplant medicine. Regina Vargha Department of Pediatrics Medical University of Vienna Vienna, Austria Heinz Regele Department of Clinical Pathology Medical University of Vienna Vienna, Austria Christoph Aufrecht Department of Pediatrics Medical University of Vienna Vienna, Austria

Induction of the stress response after inflicted and non-inflicted traumatic brain injury in infants and children.

Rapid induction of 72-kD heat shock protein (Hsp70) is a key component of the stress response and is seen after a variety of insults to the brain including experimental hyperthermia, ischemia, seizures, and traumatic brain injury (TBI). Little is known about the endogenous stress response in pediatric patients after brain injury. Accordingly, the concentration of Hsp70 was determined in 61 cerebrospinal fluid (CSF) samples from 20 infants and children after TBI. Peak Hsp70 level were increased in TBI patients vs. controls (4.60 [1.49-78.99] vs. 2.18 [1.38-4.25] ng/mL, respectively, median (range), p = 0.01) and occurred most often on day 1 after injury. Strikingly, CSF levels of Hsp70 were positively and independently associated with inflicted vs. non-inflicted TBI (7.03 [2.30-27.22] vs. 2.06 [1.06-78.99] ng/mL, respectively, p = 0.05). Endogenous Hsp70 expression was confirmed by Western blot and immunocytochemistry using brain tissue samples removed from patients who underwent decompressive craniotomy for refractory intracranial hypertension or at autopsy. These data suggest that the endogenous stress response, as measured and quantified by the Hsp70 concentration in CSF, occurs in infants and children after TBI. The endogenous stress response is more robust in victims of child abuse, compared with patients with accidental TBI, supporting age-dependence or a difference in either injury frequency, duration, severity, or mechanism in this subgroup of TBI patients. Further studies are needed to determine the role of Hsp70 in both non-inflicted and inflicted TBI in infants and children.

Heat Stress Facilitates the Recovery of Atrophied Soleus Muscle in Rat

Effects of heat stress on the recovery of atrophied soleus muscle were studied in rats. Ten-week-old male Wistar rats were randomly divided into cage control (CC) and 5-day hindlimb suspension group (HS). The half of the rats in group HS was exposed to heat stress (41 degrees C for 60 min) in an incubator immediately after the hindlimb suspension (HS-H) and the other group of rats was not heat stressed (HS-C) prior to 10 days of ambulation recovery. One group of cage control rats (CH) was also exposed to heat similarly. The soleus muscles were dissected at four time points, i.e., immediately after the suspension (or heat stress), and 3, 5, and 10 days after the recovery (n=8 per group at each time point). The absolute wet weight and water and protein content of whole soleus muscle in group HS-C were approximately 36, 27, and 8 mg less than CC (p <0.05). Thus, the percentage contribution of water and protein loss to the decrease in muscle weight was 75 and 22%, respectively. Although water content, as well as muscle weight, was elevated within 3 days, the increase of protein was delayed. Heat exposure prior to recovery accelerated the increase in protein content even in the control group. These phenomena were closely associated with 72-kD heat shock protein (HSP72) content. It is suggested that heat stress applied at the end of hindlimb unloading facilitated the recovery of atrophied soleus muscle of rat, through possibly HSP72-related events of protein metabolism. The data also indicated that the combination of heat and mechanical stress evoked larger and long lasting HSP72 response than does heat or mechanical stress alone.

Role of protein synthesis in the ischemic tolerance acquisition induced by transient forebrain ischemia in the rat.

Although ischemic preconditioning of the heart and brain is a well-documented neuroprotective phenomenon, the mechanism underlying the increased resistance to severe ischemia induced by a preceding mild ischemic exposure remains unclear. In this study we have determined the effect of ischemic preconditioning on ischemia/reperfusion-associated translation inhibition in the neocortex and hippocampus of the rat. We studied the effect of the duration on the sublethal ischemic episode (3, 4, 5 or 8 min), as well as the amount of time elapsed between sublethal and lethal ischemia on the cell death 7 days after the last ischemic episode. In addition, the rate of protein synthesis in vitro and expression of the 72-kD heat shock protein (hsp) were determined under the different experimental conditions. Our results suggest that two different mechanisms are essential for the acquisition of ischemic tolerance, at least in the CA1 sector of hippocampus. The first mechanism implies a highly significant reduction in translation inhibition after lethal ischemia, especially at an early time of reperfusion, in both vulnerable and nonvulnerable neurons. For the acquisition of full tolerance, a second mechanism, highly dependent on the time interval between preconditioning (sublethal ischemia) and lethal ischemia, is absolutely necessary; this second mechanism involves synthesis of protective proteins, which prevent the delayed death of vulnerable neurons.

Overexpression of HSP72 after induction of experimental stroke protects neurons from ischemic damage.

The 72-kD inducible heat shock protein (HSP72) can attenuate cerebral ischemic injury when overexpressed before ischemia onset. Whether HSP72 overexpression is protective when applied after ischemia onset is not known, but would have important clinical implications. Fifty-seven rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral (HSV) vectors expressing hsp72 with lacZ as a reporter were delivered 0.5, 2, and 5 hours after ischemia onset into each striatum. Control animals received an identical vector containing only lacZ. Striatal neuron survival at 2 days was improved by 23% and 15% when HSP72 vectors were delayed 0.5 and 2 hours after ischemic onset, respectively ( P < 0.05). However, when delayed by 5 hours, HSP72 overexpression was no longer protective. This is the first demonstration that HSP72 gene transfer even after ischemia onset is neuroprotective. Because expression from these HSV vectors begins 4 to 6 hours after injection, this suggests that the temporal therapeutic window for HSP72 is at least 6 hours after ischemia onset. Future strategies aimed at enhancing HSP72 expression after clinical stroke may be worth pursuing. The authors suggest that in the future HSP72 may be an effective treatment for stroke.

Important role of 72-kd heat shock protein expression in the endothelial cell in acquisition of hypoxic-ischemic tolerance in the immature rat

Objectives: Hypoxic-ischemic tolerance can be induced in neonatal rats through hyperthermic preconditioning. The purposes of this study were to determine the interval between hyperthermic preconditioning and a subsequent hypoxic-ischemic insult that would provide optimal neuroprotection against the insult and to examine the relationship between tolerance induction and heat shock protein expression. Study Design: On postnatal day 7 Wistar rat pups were separated into the following 2 groups: a heated group (those exposed to 15 minutes of hyperthermic pretreatment at a brain temperature of 41.5°C-42.0°C) and an unheated control group. At 6, 12, 24, 48, and 72 hours after the hyperthermic stress, rats from both groups were exposed to left carotid artery ligation followed by 2 hours of hypoxia (8% oxygen and 92% nitrogen) at 33°C. Twenty animals from each group were used at each time point. All rats were killed at 1 week after hypoxia-ischemia, at which time the brains were processed and neuronal damage in the cortex and hippocampus was assessed histologically. Another set of 7-day-old rats (n = 30) was studied immunohistochemically at 6, 12, 24, 48, and 72 hours after the same hyperthermic treatment. Expression of 72-kd heat shock protein was measured in neuronal, glial, and vascular endothelial cells. Results: Hyperthermia-induced hypoxic-ischemic tolerance was observed at 6, 12, and 24 hours but not at 48 and 72 hours after hyperthermic preconditioning. Heat shock protein 72 expression in the vascular endothelial cells, rather than in the glial or neuronal cells, was most strongly associated with hypoxic-ischemic tolerance. Conclusion: These findings suggest that heat shock protein 72 in endothelial cells plays an important role in the acquisition of hypoxic-ischemic tolerance at postnatal day 7, a time when maximal angiogenesis occurs and the blood-brain barrier is still immature. (Am J Obstet Gynecol 2000;182:380-6.)

Expression of the 72-kD heat shock protein is induced by ultraviolet A radiation in a human fibrosarcoma cell line.

The 72-kD heat shock protein (hsp72) belongs to a family of stress inducible proteins (heat shock proteins, hsp) and its expression is associated with increased survival of cells in culture following exposure to ultraviolet radiation (UV). Hsp72 can be induced by a number of stresses, including heat, cold, and toxic chemicals. The purpose of this study was to evaluate whether UV is able to activate transcription of hsp72. The human fibrosarcoma cell line HT1080 was used for these experiments because hsp72 is not detectable in these cells under normal culture conditions. Cells were exposed to UVA and UVB using a solar simulating source and hsp72 was determined in whole cell extracts by immunoblotting. For inhibition of mRNA and protein synthesis cordycepin (20 microg/ml) and cycloheximide (10 microg/ml) were added to the cultures, respectively. UVA-induced lipid peroxidation was inhibited by alpha-tocopherol and butylated hydroxytoluene (BHT). UVA but not UVB induced hsp72 with maximal expression at 40 J/cm2, 8-12 h after exposure. Induction was blocked by cordycepin as well as by cycloheximide indicating that both, mRNA and protein synthesis, are required for UVA-induction of hsp72. Inhibition of cell lipid peroxidation with alpha-tocopherol and BHT had no effect on hsp72 expression. These results suggest that induction of hsp72 is part of an adaptive response mechanism in human cells to UV-related stress.

Stress protein inductions after brain ischemia.

1. Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. 2. The mRNAs for 72-kd (HSP72) and 73-kd (HSC73) heat shock proteins (HSPs), which are located mainly in the cytoplasm, were greatly induced together in CA1 cells, with a peak at 1-2 days in gerbils. However, immunoreactive HSP72 protein was only minimally expressed in CA1 neurons. 3. The mRNA for mitochondrial HSP60 began to increase at 3 hr in CA1 cells and was sustained until 1 day. 4. The level of mRNA for cytochrome c oxidase subunit I (COX-I) progressively decreased in CA1 neurons after a transient ischemia and completely disappeared at 7 days. The activity of cytochrome c oxidase (COX) protein also showed an early decrease in CA1 cells and was followed by a reduction in the level of COX-I DNA after 2 days. 5. These results suggest that HSP gene inductions were inhibited at the translational level but that mitochondrial DNA expression was disturbed at the transcriptional level. A disturbance of mitochondrial DNA expression could cause progressive failure of energy production of CA1 cells that eventually results in neuronal cell death.

Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy.

Brain areas damaged by stroke and seizures express high levels of the 72-kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin-induced seizures.

Suppression of heat-induced HSF activation by CDDP in human glioblastoma cells

Purpose: The kinetics of the accumulation of inducible 72-kD heat shock protein (hsp72) and the activation of heat shock transcriptional factor (HSF) after hyperthermia and/or CDDP treatment in two human glioblastoma cell lines, A-172 having the wild-type p53 gene and T98G having the mutated p53 gene were evaluated. Methods and Materials: Western blot analysis of hsp72, gel-mobility shift assay of HSF, cell survival, and development of thermotolerance were examined. Results: The prominent suppression of heat-induced hsp72 accumulation by CDDP was seen in A-172 cells, but not in T98G cells. This was due to the p53-dependent inhibition of heat-induced HSF activation by CDDP. The interactive hyperthermic enhancement of CDDP cytotoxicity was observed in A-172 cells, but not in T98G cells. In addition, the heat-induced thermotolerance was suppressed by the presence of CDDP in the pretreatment. Conclusion: Suppression of heat-induced hsp72 accumulation by CDDP contributes to an interactive hyperthermic enhancement of CDDP cytotoxicity in the cells bearing the wild-type p53 gene.

Absence of UV-induced 72-kD heat shock protein in human melanoma cell lines

Absence of UV-induced 72-kD heat shock protein in human melanoma cell lines

The difference of HSP72 induction in rat's systemic organs after burn injury depends on burned body surface area

We have previously reported that in severely burned rats, the induction of 72-kD stress protein (HSP72) increased in various systemic organs. In this present study, in order to compare the stress response of systemic organs to burn injury of a smaller total body surface area with those of an extensive burn, we investigated the induction of 72-kD heat shock protein (HSP72) in various organs (brain, hypophysis, lung, heart, liver, pancreas, spleen, kidney, adrenal gland, and skeletal muscle) of burned rats. A dermal burn was developed on the skin by immersing the rats in hot water (90° C) for three seconds. At 0, 24 and 48 h after burn injury, the HSP72 induction of various organs was examined by Western blot analysis. In the single hind leg burn, the level of HSP72 did not increase at any time in all ten organs. In the double hind leg burn, at 48 h, the induction of HSP72 increased more than 1.5 fold compared to the control in the hypophysis (1.6 fold) and the heart (1.8 fold). These results indicate that the double hind leg burn causes a stress response in the hypophysis and the heart, while the single hind leg burn does not cause this stress response. In extensively burned rats, the degree of the stress response of the systemic organs to the burn injury depends on the burn size, and the intensity of “burn stress” to the systemic organs in a double or single hind leg burn is relatively small compared with those in extensive burns at the molecular level.

Magnesium and the N-Methyl-D-Aspartate Receptor Antagonist Dizocilpine Maleate neither Increase Glucose Use nor Induce a 72-Kilodalton Heat Shock Protein Expression in the Immature Rat Brain

In adult rats N-methyl-D-aspartate receptor (NMDAR) antagonists increase glucose use and induce a 72-kD heat shock protein (HSP72) expression in limbic system areas that later undergo neuronal necrosis, which have limited the clinical development of these drugs. Dizocilpine maleate (MK-801) and magnesium sulfate (MgSO4) reduce hypoxic-ischemic brain injury in immature animals, but the effects on HSP72 expression and glucose use are unknown. Seven-day-old rats received injections of either vehicle (control), 0.5 or 1.0 mg/kg MK-801, or 2 or 4 mmol/kg MgSO4. Glucose utilization was measured with the deoxyglucose method, 30 min, 48 h, and 4 d after injection. HSP72 immunostaining was evaluated 4 or 24 h after injection. Both doses of MK-801 and 4 mmol/kg MgSO4 induced a temporary decrease in glucose use in the posterior cingulate and retrosplenial cortex, the CA1 and CA3 subfields of the hippocampus, the caudoputamen, and the parietal cortex. Doses of 2 mmol/kg MgSO4 did not affect glucose use in any structure. Neuronal HSP72 expression was not found in any drug-treated rats. In conclusion, neither MK-801 nor MgSO4 increased glucose use in the limbic system and did not induce HSP72 expression, suggesting that NMDAR antagonists lack direct neurotoxicity in the immature brain.

Monophosphoryl Lipid A Protects Adult Rat Cardiac Myocytes With Induction of the 72-kD Heat Shock Protein: A Cellular Model of Pharmacologic Preconditioning

We examined thein vitropreconditioning effect of non-toxic derivative of endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5–7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA. Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75 mmsodium hydrosulfite, 12 mmKCl, 20 mmdl-lactic acid and 10 mm2-deoxy-D-glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH from 286±8 units/l in controls to 165±5 units/l (mean±s.e.m.;P<0.0001). Similarly, CK significantly decreased from 104±3.1 in controls to 85±1.4 U/l (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD heat shock protein in MLA treated as compared to control cells. No changes in 27, 32, and 90 kD heat shock proteins were discernible in the MLA treated group. These data suggest a significant “anti-ischemic” effect of MLA in myocytes that is accompanied by induction of 72 kD heat shock protein.

HSP72 induction of systemic organs of rats after severe burn injury

In order to understand the stress response of systemic organs to severe burn injury, the induction of 72-kD heat shock protein (HSP72) in various organs (brain, hypophysis, lung, heart, liver, pancreas, spleen, kidney, adrenal gland, and skeletal muscle) was investigated in rats with severe burns. A full-thickness burn was induced on the rats' skin by immersing the rats in hot water (90° C) for 3 s. At 0, 24, and 48 h after the burn injury, the HSP72 expression of various organs was examined using the Western blot analysis. At 24 h after the burn injury, the level of HSP72 had increased in the hypophysis, lung, heart, and kidney. In all organs examined, the expression of HSP72 had increased at 48 h after the burn injury. The level of HSP72 was highest in the hypophysis (3.3-fold compared to the control), and lowest in the brain and adrenal gland (1.7-fold of the control) at 48 h after the burn injury. These results confirm that severe burn injury causes a stress response in systemic organs.

DNA-damaging agents induce the 72-kD heat shock protein in SV40 transformed normal human fibroblasts.

In order to elucidate the involvement of DNA damage in the induction of heat shock proteins (stress proteins), we examined the induction of 72-kD heat shock protein (HSP72) in an SV40-transformed human fibroblast cell line (WI38VA13) which was exposed to various DNA-damaging agents, including 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3 -nitro-methylmethane sulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, and 4-nitroquinoline-N-oxide. Induction of HSP72 was detected by the indirect immunofluorescence method using a monoclonal antibody. All the DNA-damaging agents used in this study induced HSP72 on human fibroblasts. This result indicates that DNA damage is one trigger for the induction of HSP72.

Immune responses to the 60KD and 70KD heat shock proteins (hsp) in women: relation to fertility, history of infections, contraception and antisperm antibodies (ASA).

Immune responses to the 60KD and 70KD heat shock proteins (hsp) in women: relation to fertility, history of infections, contraception and antisperm antibodies (ASA).