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Heat shock protein-70 mediates the cytoprotective effect of carbon monoxide: involvement of p38 beta MAPK and heat shock factor-1.

Carbon monoxide (CO), a product of heme oxygenase activity, exerts antiapoptotic and anti-inflammatory effects in vitro and in vivo. The anti-inflammatory effects of CO involve the inhibition of TNF-alpha expression and the enhancement of IL-10 production, resulting in reduced mortality after endotoxin challenge. In this study we demonstrate for the first time that the protective effects of CO involve the increased expression of the 70-kDa inducible heat shock protein (Hsp70) in murine lung endothelial cells and fibroblasts. The p38beta MAPK mediated the effects of CO on cytoprotection and Hsp70 regulation. Suppression of Hsp70 expression and/or genetic deletion of heat shock factor-1, the principle transcriptional regulator of Hsp70, attenuated the cytoprotective and immunomodulatory effects of CO in mouse lung cells and in vivo. These data provide a novel mechanism for the protective effects of CO and underscore a potential application of this gaseous molecule in anti-inflammatory therapies.

Active Transport, Cell Nucleus↗

Genetic and environmental factors in the resistance of Drosophila subobscura adults to high temperature shock. III. Chromosomal-inversion and enzymatic polymorphism variation in lines selected for heat shock resistance.

Two replicate selection experiments to increase and decrease heat shock resistance of Drosophila subobscura adults were carried out maintaining control lines. In the present paper, the chromosomal-inversion and enzymatic polymorphism variation with selection is analyzed. The results indicate an erratic variation of chromosomal arrangement frequencies for practically all the chromosomes in the selected lines, showing a loss of the less frequent arrangements especially in sensitive lines. Only the A chromosome and the O + 4 arrangement show a behaviour that may not be due to random effects, which points to the possible existence of heat shock factor(s) in these chromosomes. Similarly, an erratic variation of allele frequencies is observed for all the enzymes studied (Aph, Pept-1) except for the Hk-1 enzyme. We cannot establish the possible participation of this locus in heat shock resistance from the results obtained up to now. A significant decrease in heterozygosity is detected in sensitive lines from chromosomal-inversion polymorphism.

Animals↗

The products of the "heat-shock" loci of Drosophila hydei. Correlation between locus 2-36A and the 70,000 MW "heat-shock" peptide.

Antibody was raised against total Drosophila hydei embryonic cellular protein with a molecular weight between 65,000 and 70,000 dalton. This antiserum reacted with the 70,000 MW "heat-shock" peptide found in "S labelled cell extracts of "heat-shocked" D. hydei tissue culture cells or salivary glands.--The antibody was coupled to Sepharose 4B and this material was used to absorb polysomes obtained from tissue culture cells incubated at 37 degrees C in the presence of tritiated RNA precursors. The relative concentrations of various RNA species complementary to the "heat-shock" loci 2-32A, 2-36A, and 2-48C in either bound, non-bound, or total polysomal material was then determined by in situ hybridization. The RNA species complementary to locus 2-36A was found to be enriched in the bound polysomal material.

Animals↗

Ecdysterone and heat shock induction of transfecting and endogenous heat shock genes in cultured Drosophila cells.

Various combinations of the heat shock genes of Drosophila melanogaster are transcribed in response to elevated temperature and also during normal development and in certain ecdysterone-treated Drosophila cell lines. Here I describe an homologous transient expression system using Schneider 3 cells, a Drosophila line responsive to ecdysterone. I compare the constitutive, ecdysterone and heat shock-induced accumulation of transcripts of five transfecting heat shock genes (hsp82, hsp70, hsp28, hsp26 and hsp23) to the accumulation of transcripts of their endogenous counterparts. The pattern of expression of the transfecting genes under these various conditions is generally similar to that of the endogenous genes.

Animals↗

Unique influences of ten drugs upon post-shock biting attack and pre-shock manual responding.

Delivery of a fixed-time, response-independent electric tail shock to the squirrel monkey generated bites on a rubber hose immediately following shock and manual responses on a lever immediately preceding shock; two temporally and topographically different responses in a single organism in a single experimental session. d-Amphetamine, cocaine, and caffeine each had the effect of elevating both bite and lever press responses; nicotine, chlorpromazine, chlordiazepoxide, and diazepam each elevated lever press responding while depressing bite responding across a portion of the dosage range; phenobarbital, alcohol, and morphine had the effect of depressing both bite and lever press responses but lever pressing was selectively more depressed than biting. The results parallel previous research with these drugs on other measures of aggression and on other behavioral paradigms. The responses are contingency free so that the effect of a drug does not interact with response produced environmental consequences. The recording of two separate responses related to distinct emotional states from one organism in a single experimental session allows for the objective measurement of selective and differential drug effects.

Aggression↗

Biological effects of shock waves: lung hemorrhage by shock waves in dogs--pressure dependence.

The most serious side effect observed during the destruction of gallstones by shock waves in dogs was lung bleeding. To determine the conditions leading to lung damage, pressure probes were implanted into dogs between the lung and the diaphragm. The distance between the lung and the focal point of the pressure field was determined at which 1000 shock waves caused no more lung hemorrhage. On the long axis it is greater than 15 cm and perpendicular to the long axis it is 4 cm. Shock wave pressures over 2 MPa could be administered safely, whereas a pressure of 10 MPa caused bleedings in beagles, but probably not in boxers.

Animals↗

Mechanisms of pain associated with internal defibrillation shocks: results of a randomized study of shock waveform.

BACKGROUND: Shock pain has limited the acceptance of the implantable atrial cardioverter and is a complication of ventricular implantable cardioverter-defibrillator therapy. Rounding off of the peak of a shock waveform reduces pain. Whether the pain reduction results from reduction in the peak voltage or from the rounding has not been established. In other words, does reducing the extreme dV/dt (voltage derivative) of the conventional truncated exponential capacitive discharge waveform reduce pain? OBJECTIVES: The purpose of this study was to compare the relative contributions of peak voltage and waveform shape to pain. METHODS: We compared rounded and conventional waveforms with equal peak voltages. Eighty-five shocks of 50 to 500 V were delivered to 10 patients requiring atrial cardioversion for persistent atrial fibrillation. The patient touched an analog pain scale (0-15 cm) and orally reported a pain score on a scale from 0 to 5. An observer scored thoracic contractions on a scale from 0 to 5. RESULTS: No differences between the rounded and conventional waveform on any scale were noted for either univariate or multivariate analyses. However, all three response scales were strongly predicted by voltage with r(2) = 0.77 (oral), r(2) = 0.86 (analog), and r(2) = 0.85 (contraction) after correcting for patient variability and including a log voltage term. CONCLUSIONS: Patient pain perception was determined primarily by waveform peak voltage and not by the rounding, per se.

Adult↗

Drought acclimation and lipid composition in Folsomia candida: implications for cold shock, heat shock and acute desiccation stress.

Many of the physiological adaptations evolved in terrestrial invertebrates to resist desiccation have also been shown to enhance the survival of low temperatures. In this study we have examined temporal changes in the physiology of the collembolan Folsomia candida during acclimation to mild desiccation stress (98.2% RH), and how physiological changes correlate with resistance to subsequent cold shock, heat shock and acute desiccation stress. Drought-acclimation increased the resistance to cold and acute drought but reduced the resistance to heat shock. The composition of membrane phospholipid fatty acids (PLFA) changed during acclimation resulting in a higher degree of unsaturation by the end of the 192-h acclimation period. This resembles typical membrane alterations seen in ectothermic animals exposed to cold. Only small changes were seen in the neutral lipid fraction. The temporal changes in cold resistance and drought resistance correlated well with changes in PLFA composition and accumulation of sugars and polyols ('cryoprotectives'). It is proposed that the drought-induced PLFA desaturation, combined with the membrane protecting accumulation of cryoprotectives, are important physiological adaptations providing tolerance to both desiccation and cold.

Journal Article↗

Shock-absorbing and failure mechanisms of WS2 and MoS2 nanoparticles with fullerene-like structures under shock wave pressure.

The excellent shock-absorbing performance of WS2 and MoS2 nanoparticles with inorganic fullerene-like structures (IFs) under very high shock wave pressures of 25 GPa is described. The combined techniques of X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, thermal analysis, and transmission electron microscopy have been used to evaluate the diverse, intriguing features of shock recovered IFs, of interest for their tribological applications, thereby allowing improved understanding of their antishock behavior and structure-property relationships. Two possible failure mechanisms are proposed and discussed. The supershock-absorbing ability of the IF-WS2 enables them to survive pressures up to 25 GPa accompanied with concurrent temperatures of up to 1000 degrees C without any significant structural degradation or phase change making them probably the strongest cage molecules now known.

Journal Article↗

The physics of liquid impact, shock wave interactions with cavities, and the implications to shock wave lithotripsy.

This paper reviews research on the physics of liquid impact and the behaviour of cavities when a shock passes over them. It is shown that the problems are related since when a cavity collapses near a solid surface, or is collapsed by a shock wave, the collapse is asymmetric and a liquid jet is produced which can impact an adjacent solid. The implications of this research to shock wave lithotripsy are emphasized. Finally, the paper describes the development of a device, based on liquid jet impact, for fragmenting kidney stones.

Humans↗

Heat shock-induced repression of proteolysis: poly(A)-binding protein degradation patterns can illusorily suggest its specific loss during heat shock.

Poly(A)-binding protein (PABP) is highly susceptible to proteolysis during cell lysis of Drosophila tissue culture cells unless substantial amounts of proteolysis inhibitors are included in the extraction buffer. This intrinsic proteolytic activity is substantially reduced during heat shock. An artifactual appearance that poly(A)-binding protein is specifically degraded by heat shock can result. Several contradictory descriptions of PABP may also be related to its proteolysis. Repression of proteolysis is likely to reflect a physiologically significant regulatory event, based on recent examinations of HSP70 stability during and after heat shock.

Animals↗

Anaphylactic shock: a form of distributive shock without inhibition of oxygen consumption.

BACKGROUND: The pathophysiology of anaphylactic shock during anesthesia is incompletely characterized. It is described as distributive by analogy with septic shock (anaerobic metabolism, high tissue oxygen pressure [Ptio2] values). The Ptio2 profile and its metabolic consequences during anaphylaxis are not known. METHODS: Ovalbumin-sensitized anaphylactic shock rats (n = 11) were compared to nicardipine-induced hypotension rats (n = 12) for systemic hemodynamics, Ptio2, sympathetic nervous system activation, skeletal muscle blood flow, and interstitial lactate and pyruvate concentrations using combined microdialysis and polarographic Clark-type oxygen probes. RESULTS: In both groups, the time course and the magnitude of arterial hypotension were similar. The ovalbumin group but not the nicardipine group displayed decreased skeletal muscle blood flow (from 45 +/- 6.2 ml x 100 g(-1) x min(-1) to 24.3 +/- 5 ml x 100 g(-1) x min(-1); P < 0.0001) and Ptio2 values (from 42 +/- 5 to 5 +/- 2; P < 0.0001). The ovalbumin group had more intense sympathetic nervous system activation with higher plasma epinephrine and interstitial norepinephrine concentrations. For the ovalbumin group, there was skeletal muscle anaerobic metabolism (lactate concentration increased from 0.446 +/- 0.105 to 1.741 +/- 0.459 mm; P < 0.05) and substrate depletion (pyruvate concentration decreased from 0.034 +/- 0.01 mm to 0.006 +/- 0.002 mm; P < 0.05) leading to increased interstitial lactate/pyruvate ratios (from 17 +/- 6 to 311 +/- 115; P < 0.05). CONCLUSIONS: This profile suggests decreased skeletal muscle blood flow and oxygen delivery. Persistent energy consumption results in decreased Ptio2 and substrate depletion through anaerobic glycolysis leading to complete failure of cellular energy production. This could explain rapid organ dysfunction and resuscitation difficulties.

Anaphylaxis↗

Propagation of shock waves in elastic solids caused by cavitation microjet impact. II: Application in extracorporeal shock wave lithotripsy.

To better understand the mechanism of stone fragmentation during extracorporeal shock wave lithotripsy (ESWL), the model developed in Part I [P. Zhong and C.J. Chuong, J. Acoust. Soc. Am. 94, 19-28 (1993)] is applied to study cavitation microjet impingement and its resultant shock wave propagation in renal calculi. Impact pressure at the stone boundary and stress, strain at the propagating shock fronts in the stone were calculated for typical ESWL loading conditions. At the anterior surface of the stone, the jet induced compressive stress can vary from 0.82 approximately 4 times that of the water hammer pressure depending on the contact angles; whereas the jet-induced shear stress can achieve its maximum, with a magnitude of 30% approximately 54% of the water hammer pressure, near the detachment of the longitudinal (or P) wave in the solid. Comparison of model predictions with material failure strengths of renal calculi suggests that jet impact can lead to stone surface erosion by combined compressive and shear loadings at the jet impacting surface, and spalling failure by tensile forces at the distal surface of the stone. Comparing responses from four different stone types suggests that cystine is the most difficult stone to fragment in ESWL, as observed from clinical experience.

Kidney Calculi↗

Nuclear export of heat shock and non-heat-shock mRNA occurs via similar pathways.

Several studies of the yeast Saccharomyces cerevisiae support differential regulation of heat shock mRNA (hs mRNA) and non-hs mRNA nuclear export during stress. These include the finding that hs mRNA export at 42 degrees C is inhibited in the absence of the nucleoporinlike protein Rip1p (also called Nup42p) (C. A. Saavedra, C. M. Hammell, C. V. Heath, and C. N. Cole, Genes Dev. 11:2845-2856, 1997; F. Stutz, J. Kantor, D. Zhang, T. McCarthy, M. Neville, and M. Rosbash, Genes Dev. 11:2857-2868, 1997). However, the results reported in this paper provide little evidence for selective non-hs mRNA retention or selective hs mRNA export under heat shock conditions. First, we do not detect a block to non-hs mRNA export at 42 degrees C in a wild-type strain. Second, hs mRNA export appears to be mediated by the Ran system and several other factors previously reported to be important for general mRNA export. Third, the export of non-hs mRNA as well as hs mRNA is inhibited in the absence of Rip1p at 42 degrees C. As a corollary, we find no evidence for cis-acting hs mRNA sequences that promote transport during heat shock. Taken together, our data suggest that a shift to 42 degrees C in the absence of Rip1p impacts a late stage of transport affecting most if not all mRNA.

Biological Transport↗

Expression of the 60 kDa and 71 kDa heat shock proteins and presence of antibodies against the 71 kDa heat shock protein in pediatric patients with immune thrombocytopenic purpura.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against platelet proteins, particularly platelet glycoprotein IIb/IIIa. Heat shock proteins (Hsp) have been shown to be major antigenic determinants in some autoimmune diseases. Antibodies to Hsps have also been reported to be associated with a number of pathological states. METHODS: Using western blot, we measured the levels of the 60 kDa heat shock protein (Hsp60) and of the inducible 71 kDa member of the Hsp70 family (Hsp71) in lymphocytes and the presence of antibodies against these hsps in plasma of 29 pediatric patients with ITP before the treatment and in 6 other patients before and after treatment. RESULTS: Interestingly only one out of 29 patients showed detectable Hsp60 in lymphocytes while this heat shock protein was detected in the 30 control children. Hsp71 levels were slightly lower in lymphocytes of patients with ITP than in controls (1567.8 ± 753.2 via 1763.2 ± 641.8 integrated optical density (IOD) units). There was a small increase of Hsp71 after recovery from ITP. The titers of plasma antibodies against Hsp60 and Hsp71 were also examined. Antibodies against Hsp71 were more common in ITP patients (15/29) than in control children (5/30). The titer of anti-Hsp71 was also higher in children patients with ITP. The prevalence of ITP children with antibodies against Hsp71 (51.7%) was as high as those with antibodies against platelet membrane glycoproteins (58.3%). CONCLUSIONS: In summary, pediatric patients with ITP showed no detectable expression of Hsp60 in lymphocytes and a high prevalence of antibody against Hsp71 in plasma. These changes add to our understanding of the pathogenesis of ITP and may be important for the diagnosis, prognosis and treatment of ITP.

Journal Article↗

Expression of the heat shock gene clpL of Streptococcus thermophilus is induced by both heat and cold shock.

BACKGROUND: Heat and cold shock response are normally considered as independent phenomena. A small amount of evidence suggests instead that interactions may exist between them in two Lactococcus strains. RESULTS: We show the occurrence of molecular relationships between the mechanisms of cold and heat adaptations in Streptococcus thermophilus, a lactic acid bacterium widely used in dairy fermentation, where it undergoes both types of stress. We observed that cryotolerance is increased when cells are pre-incubated at high temperature. In addition, the production of a protein, identified as ClpL, a member of the heat-shock ATPase family Clp A/B, is induced at both high and low temperature. A knock-out clpL mutant is deficient in both heat and cold tolerance. However lack of production of this protein does not abolish the positive effect of heat pre-treatment towards cryotolerance. CONCLUSION: Dual induction of ClpL by cold and heat exposure of cells and reduced tolerance to both temperature shocks in a clpL mutant indicates that the two stress responses are correlated in S. thermophilus. However this protein is not responsible by itself for cryotolerance of cells pre-treated at high temperature, indicating that ClpL is necessary for the two phenomena, but does not account by itself for the relationships between them.

Journal Article↗

The release of catecholamines by shocks and stimuli paired with shocks.

One monkey and five baboons were surgically prepared so that heart rate and blood pressure could be monitored continuously, and an extra-corporeal blood path was established to detect the secretion of epinephrine (adrenaline) and norepinephrine (noradrenaline). A respondent conditioning procedure was used in which a tone was paired with electric shocks. Epinephrine, but not norepinephrine was released by shocks, and a corresponding release was demonstrated by the tone alone. Heart rate and blood pressure changes were also elicited by shocks and by the tone.

Animals↗