Biomedical subjects

A De Maio

Publications and source records attributed to A De Maio.

At least 19 recordsLinked to original sources

PubMed2006

Carbon dioxide pneumoperitoneum prevents mortality from sepsis.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum has been shown to attenuate the inflammatory response after laparoscopy. This study tested the hypothesis that abdominal insufflation with CO2 improves survival in an animal model of sepsis and investigated the associated mechanism. METHODS: The effect of CO2, helium, and air pneumoperitoneum on mortality was studied by inducing sepsis in 143 rats via intravenous injection of lipopolysaccharide (LPS). To test the protective effect of CO2 in the setting of a laparotomy, an additional 65 animals were subjected to CO2 pneumoperitoneum, helium pneumoperitoneum, or the control condition after laparotomy and intraperitoneal LPS injection. The mechanism of CO2 protection was investigated in another 84 animals. Statistical significance was determined via Kaplan-Meier analysis for survival and analysis of variance (ANOVA) for serum cytokines. RESULTS: Among rats with LPS-induced sepsis, CO2 pneumoperitoneum increased survival to 78%, as compared with using helium pneumoperitoneum (52%; p < 0.05), air pneumoperitoneum (55%; p = 0.09), anesthesia control (50%; p < 0.05), and LPS-only control (42%; p < 0.01). Carbon dioxide insufflation also significantly increased survival over the control condition (85% vs 25%; p < 0.05) among laparotomized septic animals, whereas helium insufflation did not (65% survival). Carbon dioxide insufflation increased plasma interleukin-10 (IL-10) levels by 35% compared with helium pneumoperitoneum (p < 0.05), and by 34% compared with anesthesia control (p < 0.05) 90 min after LPS stimulation. Carbon dioxide pneumoperitoneum resulted in a threefold reduction in tumor necrosis factor-alpha (TNF-alpha) compared with helium pneumoperitoneum (p < 0.05), and a sixfold reduction with anesthesia control (p < 0.001). CONCLUSION: Abdominal insufflation with CO2, but not helium or air, significantly reduces mortality among animals with LPS-induced sepsis. Furthermore, CO2 pneumoperitoneum rescues animals from abdominal sepsis after a laparotomy. Because IL-10 is known to downregulate TNF-alpha, the increase in IL-10 and the decrease in TNF-alpha found among the CO2-insufflated animals in our study provide evidence for a mechanism whereby CO2 pneumoperitoneum reduces mortality via IL-10-mediated downregulation of TNF-alpha.

Abdomen↗

PubMed2006

Laparoscopic surgery and the parasympathetic nervous system.

BACKGROUND: Laparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway. METHODS: In the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments. CONCLUSION: CO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.

Animals↗

PubMed2004

The effect of timing of pneumoperitoneum on the inflammatory response.

BACKGROUND: We examined the effects of an identical period of pneumoperitoneum applied at three different time points after lipopolysaccharide (LPS) challenge. Two different insufflation gases were also compared. METHODS: Male rats (n = 70) were injected intravenously with 1 mg/kg of LPS (time 0). The time relationship between a 1.5-h period of insufflation and initial LPS stimulation was the experimental variable. All rats were killed 6 h after injection. CO2 and helium insufflation were investigated. Ten control rats received LPS only. Serum interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assay (ELISA). Hepatic expression of alpha2-macroglobulin, beta-fibrinogen, and metallothionein were measured by Northern blot analysis. Statistical analysis was performed using one-way analysis of variance (ANOVA). RESULTS: Expression of alpha2-macroglobulin mRNA was lower in CO2 groups compared to the control group (p < 0.05 at time 120 and 270). beta-Fibrinogen message was diminished in CO2 0 and 120 groups compared to control. Serum levels of IL-6 and expression of metallothionein mRNA did not show significant differences between groups. CONCLUSIONS: These findings suggest that CO2 pneumoperitoneum downregulates the inflammatory response to LPS challenge. Start time of CO2 insufflation does not appear to alter hepatic expression of acute phase genes. The mechanism of alpha2-macroglobulin downregulation does not appear to be due to IL-6.

Animals↗

PubMed2003

In vitro studies of the influence of ELF electromagnetic fields on the activity of soluble and insoluble peroxidase.

The influence of an extremely low frequency (ELF) magnetic field (50 Hz and 1 mT, EMF) on the activity of a soluble and insoluble horseradish peroxidase (E.C. 1.11.17) has been studied as a function of time. Insoluble derivatives were obtained by enzyme entrapment into two different gelatin membranes or by covalent attachment of the enzyme on two nylon membranes, differently preactivated. Results have shown that the field affects the inactivation rate of the soluble enzyme, while no effects are observed with insoluble derivatives. Since in vivo enzymes are immobilised into the biomembrane bilayer or entrapped into the cytoplasmic mixture, one might speculate that our experimental conditions do not reflect the catalytic activity of the enzymes in vivo.

Benzothiazoles↗

PubMed2002

Advantages of using non-isothermal bioreactors for the enzymatic synthesis of antibiotics: the penicillin G acylase as enzyme model.

A new hydrophobic and catalytic membrane was prepared by immobilizing Penicillin G acylase (PGA, EC.3.5.1.11) from E. coli on a nylon membrane, chemically grafted with butylmethacrylate (BMA). Hexamethylenediamine (HMDA) and glutaraldehyde (Glu) were used as a spacer and coupling agent, respectively. PGA was used for the enzymatic synthesis of cephalexin, using D(-)-phenylglycine methyl ester (PGME) and 7-amino-3-deacetoxycephalosporanic acid (7-ADCA) as substrates. Several factors affecting this reaction, such as pH, temperature, and concentrations of substrates were investigated. The results indicated good enzyme-binding efficiency of the pre-treated membrane, and an increased stability of the immobilized PGA towards pH and temperature. Calculation of the activation energies showed that cephalexin production by the immobilized biocatalyst was limited by diffusion, resulting in a decrease of enzyme activity and substrate affinity. Temperature gradients were employed as a way to reduce the effects of diffusion limitation. Cephalexin was found to linearly increase with the applied temperature gradient. A temperature difference of about 3 degrees C across the catalytic membrane resulted into a cephalexin synthesis increase of 100% with a 50% reduction of the production times. The advantage of using non-isothermal bioreactors in biotechnological processes, including pharmaceutical applications, is also discussed.

Anti-Bacterial Agents↗

PubMed2002

Carbon dioxide pneumoperitoneum alters acute-phase response induced by lipopolysaccharide.

BACKGROUND: As laparoscopic surgery continues to expand in scope, septic patients will be exposed to carbon dioxide (CO2) pneumoperitoneum in increasing numbers. The biologic advantages or disadvantages of laparoscopic surgery in the setting of sepsis/inflammation are not known. In a rat model, we investigated whether CO2 pneumoperitoneum alters the inflammatory response induced by bacterial lipopolysaccharide (LPS). METHODS: Male rats were injected via the penile vein with LPS (1 mg/kg). Five hours later, the animals (n = 5) were subjected to CO2 pneumoperitoneum (group I) for 1h; the animals of group II (n = 5) served as controls (no pneumoperitoneum). At 6 h, all animals were killed and the liver harvested for analysis of hepatic acute-phase gene expression. Total RNA was isolated and analyzed by Northern blot hybridization with probes for alpha-2 macroglobulin (A2M) and detected by autoradiography. The film in the linear range of exposure was quantitated using an imaging system. The signal intensity corresponding to A2M mRNA was normalized by the signal corresponding to 28S rRNA detected by staining with methylene blue. RESULTS: The mRNA levels in group II was 6.5 +/- 0.9 vs 2.8 +/- 0.4 in group I. As compared with rats that received LPS only, those that received a combination of LPS and CO2 showed a reduction in A2M mRNA levels (57.4%, p = 0.006). CONCLUSIONS: These data demonstrate that the presence of CO2 pneumoperitoneum reduces the inflammatory response established by LPS. This finding challenges the generally accepted notion that smaller incisions alone account for the observed benefits of laparoscopic surgery. It further suggests that CO2 pneumoperitoneum - aided laparoscopic surgery impedes the inflammatory response and may therefore offer specific benefits over conventional surgery.

Acute-Phase Reaction↗

PubMed2002

The alpha1-antitrypsin/elastase complex as an experimental model for hemodialysis in acute catabolic renal failure, extracorporeal blood circulation and cardiocirculatory bypass.

A modified polyethersulphone graft membrane was loaded with antiproteases, with the aim of reducing the active protease blood concentration during hemodialysis in acute catabolic renal failure or cardiopulmonary bypass. As protease/antiprotease system, elastase and alpha1-antitrypsin were used. The concentration of active elastase in aqueous solutions decreased as function of contact time with the membrane, approaching saturation. A 40% loss of elastase activity was obtained at pH 7.4, which was not due to autolysis, which accounted for 5% of the loss. The highest reduction was achieved at pH 9.0 (25% higher than at pH 7.4). The saturation level of elastase decrease, calculated by means of the Einstein equation, was reached after more than 47 minutes. We speculate that a time reduction might be achieved either increasing the concentration of immobilized antiproteases, or increasing the rate of elastase movement across the membranes by hydraulic, osmotic, or temperature gradients. This technology can be applied to hemodialysis, and in extracorporeal blood circulation to promote elastase release.

Acute Kidney Injury↗

PubMed2001

Isothermal and non-isothermal characterization of catalytic nylon membranes chemically grafted: dependence on the grafting percentage.

The behaviour of five different hydrophobic beta-galactosidase derivatives, obtained by grafting different amount of butylmethacrylate (BMA) on planar nylon membranes, has been studied under isothermal and non-isothermal conditions.Under isothermal conditions the effect of the grafting percentage on the enzyme activity has been studied as a function of pH, temperature and substrate concentration. Independently from the parameters under observation, the yield of the catalytic process reaches the maximum value at a grafting percentage value equal to 21%. The apparent K(m) values result linearly increasing with the increase of the grafting percentage, while the apparent V(max) exhibits a maximum value.Under non-isothermal conditions, a decrease of the apparent K(m) values and increase of the apparent V(max) has been found in respect to the same values obtained under isothermal conditions.The percentage activity increases induced by the presence of a temperature gradient have been found to decrease with the increase of the percentage of graft BMA.A parameter correlating the percentage increase of enzyme activity under non-isothermal conditions with the hydrophobicity of the catalytic membrane has also been identified. This parameter is the ratio between thermoosmotic and hydraulic permeability.Results have been discussed in terms of reduction of diffusion limitations for substrate and products movement towards or away from the catalytic site by the process of thermodialysis.The usefulness of using non-isothermal bioreactors in industrial biotechnological processes has been confirmed.

Journal Article↗

PubMed2001

Promoter activity of the rat connexin 43 gene in NRK cells.

Cellular communication mediated by gap junctions plays a major role in organ function. Gap junction channels are formed by the organization of polypeptide subunits, termed connexins (Cx), on the cell surface of adjacent cells. One mechanism to regulate gap-junctional communication is by change in Cx expression. In the present study, the promoter region of the rat Cx43 gene was characterized. Nested deletions of the 5' flanking region of the first Cx43 exon were coupled to the human growth hormone gene and transfected into normal rat kidney (NRK) cells, that express this gene constitutively. The minimal region of the Cx43 gene that showed maximal promoter activity was localized within 110 bp upstream of the transcriptional initiation site. One particular subregion that contains a Sp-1 binding site (located within 98--93 bp from the transcriptional initiation site) was found to sustain Cx43 promoter activity to the same extent as that of the 110 bp promoter region. Mutations of this Sp-1 binding site abolished transcriptional activity and DNA-protein interactions. These observations suggest that the Sp-1 binding site plays a major role in the basal transcriptional activity of Cx43 gene in NRK cells.

Animals↗

PubMed2000

ATP and ADP modulate a cation channel formed by Hsc70 in acidic phospholipid membranes.

Heat shock proteins are molecular chaperones that participate in different cellular processes, particularly the folding and translocation of polypeptides across membranes. In this regard, members of the Hsp70 family of heat shock proteins have been observed in close proximity to cellular membranes. In this study, the direct interaction between Hsc70, which is constitutively expressed in cells, and lipid membranes was investigated. Recombinant Hsc70 was incorporated into artificial lipid bilayers, and a transmembrane ion flow was detected, suggesting the incorporation of an ion pathway. This ion flow was very stable and occurred in well defined, multilevel discrete electrical current events, indicating the formation of a multiconductance ion channel. The Hsc70 channel activity is ATP-dependent and is reversibly blocked by ADP. This channel has cationic selectivity. Thus, Hsc70 can directly interact with lipid membranes to create functionally stable ATP-dependent cationic pathways.

Adenosine Diphosphate↗

PubMed2000

Comparison of the stress response after laparoscopic and open cholecystectomy.

BACKGROUND: We designed a prospective controlled animal study to compare the stress response induced after laparoscopic and open cholecystectomy. METHODS: Twelve female pigs (20-25 kg body weight) were anesthetized with ketamine, pentobarbital, and fentanyl. The animals were randomized into the following four groups: control (C), pneumoperitoneum with CO(2) at 14-15 mmHg (P), laparoscopic cholecystectomy (LC), and open cholecystectomy (OC). The average duration of the procedure in each group was 35 min. RESULTS: Central venous pressure, mean arterial pressure, pulmonary capillary wedge pressure, and cardiac output were monitored. Measurements were recorded when animals were anesthetized (baseline), immediately before and after surgery, and thereafter every 30 min for a maximum of 3 h. White blood cell count (WBC) was determined from blood samples taken before and after 3 h of surgery. Ultrasound-guided liver biopsies were done preoperatively and after 3 h of surgery. Total RNA was isolated from the liver biopsy specimens. Steady-state mRNA levels of beta-fibrinogen (beta-fib), alpha 1-chymotrypsin inhibitor (alpha1-CTI), metallothionein (MT), heat shock protein 70 (Hsp70), and polyubiquitin (Ub) were detected by Northern blot/hybridization. There were no statistical differences in the hemodynamic parameters among the groups. The number of circulating neutrophils and monocytes decreased only after LC. Expression of Hsp70 was not induced after any surgical procedure, and the mRNA levels of Ub did not change after surgery. The expression of alpha1-CTI and beta-fib (acute phase genes) were similarly increased after LC and OC. Steady-state mRNA levels of MT were slightly increased after P and LC but not after OC. CONCLUSION: These data indicate that there are no significant differences between LC and OC in terms of induction of the stress response.

Analysis of Variance↗

PubMed2000

Quantitative trait loci modulate neutrophil infiltration in the liver during LPS-induced inflammation.

A crucial aspect of the inflammatory response is the recruitment of activated neutrophils (PMN) to the site of damage. Lytic enzymes and oxygen radicals released by PMN are important in clearing an infection or cellular debris, but can also produce host tissue damage. Failure to properly regulate the inflammatory response contributes to a variety of human diseases like sepsis and multiple organ dysfunction syndrome, the leading cause of morbidity and mortality in surgical intensive care units. Many aspects of human disease pathology, including hepatic PMN infiltration, can be recapitulated in mice using an endotoxic shock model. Six quantitative trait loci that predispose to high infiltration of PMN in hepatic sinusoids after high-dose endotoxin administration were provisionally identified. Two of these loci, Hpi1 and Hpi2 on mouse chromosomes 5 and 13, were mapped to the significant and highly significant level using a low-resolution genome scan on 122 intercross animals. These loci interact epistatically to produce a high degree of PMN infiltration. Intercross and recombinant inbred strain mice with a specific genotype at these loci always had a high infiltration response, indicating that genotype analysis at just these two loci can accurately predict a high PMN infiltration response. Genetic predisposition to the degree of PMN infiltration in the inflammatory response in mice suggests that analogous genetic mechanisms occur in human beings that could be used for diagnostic purposes.

Animals↗

PubMed2000

Interruption of hepatic gap junctional communication in the rat during inflammation induced by bacterial lipopolysaccharide.

Gap junctional cellular communication is important in the propagation of signals that coordinate hepatic metabolism. Hepatocytes express two different connexin (Cx) genes, Cx32 and Cx26, which encode for the subunit component of gap junction channels. Previous studies have shown that the expression of hepatic Cx32 is reduced during inflammatory conditions. The objective of this study was to evaluate whether this decrease in Cx32 expression results in a decrease in hepatic gap junctional communication. Transfer of the dye Lucifer Yellow between hepatocytes was measured after microinjection of single cells in an isolated perfused liver. Livers were harvested from rats subjected to an inflammatory condition induced by administration of bacterial lipopolysaccharide (LPS). A decrease in gap junctional cellular communication was observed within 6 h of the LPS treatment. This decrease in dye coupling was reversible, because gap junctional communication returned to control levels within 48 h of the LPS injection. The inhibition of hepatic gap junctional communication was associated with the disappearance of Cx32 and Cx26 from the hepatocyte plasma membrane as detected by indirect immunostaining. Cx32 mRNA levels were also reduced during inflammation as previously reported. However, Cx26 mRNA levels were unaffected or even transiently increased after the injection of LPS without significant increase in the polypeptide level. Thus, the down-regulation of Cx32 and Cx26 from the hepatocyte surface is apparently due to a rapid degradation of the polypeptide from the cell surface. We hypothesize that this loss of gap junctional cellular communication within the liver may contribute to the disordered hepatic metabolic that occurs during inflammatory states.

Animals↗

PubMed1999

Mapping lipopolysaccharide response loci in mice using recombinant inbred and congenic strains.

Lipopolysaccharide (LPS) induces proliferation of splenic B-cells, and this response was found to be significantly lower in A/J than in C57BL/6J (B6) mice. Several strains and substrains mirrored the high and low responses of B6 and A/J. Assessment of 26 AXB/BXA recombinant inbred (RI) mouse strains identified 23 strains with a low (A/J-like), high (B6-like), or intermediate response. The three remaining RI strains exhibited a novel hyperresponsive phenotype significantly different from that of either founder strain. RI analysis identified four suggestive loci contributing to the LPS response, two of which were confirmed by analysis of congenic strains containing the donor genomic segment from a high- or low-responder strain on the opposite background. The combination of A/J and B6 alleles fixed to homozygosity at the four suggestive loci would occur in only 1 of 256 intercross progeny, but occurred several times among the RI strains.

Alleles↗

PubMed1999

Thermotolerant cells show an attenuated expression of Hsp70 after heat shock.

Expression of heat shock proteins (hsps) results in the protection of cells from subsequent stresses. However, hsps are also toxic when present within cells for a prolonged time period. Thus, the expression of hsps should be tightly regulated. In the present study, the expression of Hsp70 after heat shock was compared between thermotolerant cells, which contain a large concentration of Hsp70, and nonthermotolerant cells (naive). Accumulation of Hsp70, assessed by Western blotting, was negligible when thermotolerant cells were heat-shocked a second time. Hsp70 transcription was similar between thermotolerant and naive cells during heat shock. However, Hsp70 transcription was attenuated more rapidly in thermotolerant than naive cells immediately upon return to non-heat shock conditions. In addition, Hsp70 mRNA stability was reduced in thermotolerant cells as compared with naive cells following the stress. New synthesis of Hsp70 and the efficiency of Hsp70 mRNA translation were similar between thermotolerant and naive cells during the post-stress period. These results suggest that thermotolerant cells limit Hsp70 expression by transcriptional and pretranslational mechanisms, perhaps to avoid the potential cytotoxic effect of these proteins.

Adaptation, Physiological↗

PubMed1999

Downregulation of connexin 43 gene expression in rat heart during inflammation. The role of tumour necrosis factor.

Gap junctions form channels that mediate the communication between adjacent cells. Alterations in gap junction function and/or expression are believed to contribute to cardiac dysfunction such as those observed in septic patients. The expression of connexin 43 (Cx43), the subunit component of the most abundant cardiac gap junction, was analysed in rat heart during inflammation induced by the administration of bacterial lipopolysaccharide (LPS). Cx43 mRNA levels were found to be dramatically (>50%) and rapidly (2 h) reduced in the heart after injection of LPS (1 mg/kg). To investigate the possible mechanism of the decrease in Cx43 expression during inflammation, the promoter region of this gene was cloned. The basal Cx43 promoter activity was observed within 224-134 bp of the transcriptional initiation site after transfection into a rat myoblast cell-line (H9c2). The Cx43 promoter activity was found to be reduced by incubation of the transfected cells with serum obtained from LPS-treated rats. Moreover, Cx43 promoter activity was also decreased upon incubation with tumour necrosis factor alpha. These results suggest that Cx43 expression in the heart can be modulated by circulating cytokines. These observations may have important implications in the depression of heart function observed in septic patients.

Animals↗

PubMed1999

Heat shock proteins: facts, thoughts, and dreams.

The most primitive mechanism of cellular protection involves the expression of a polypeptide family named heat shock or stress proteins (hsps). Some of these hsps are present in unstressed cells and play an important role in the folding and translocation of polypeptides across membranes. Thus, they have been termed molecular chaperones. Hsps are expressed in response to an array of stresses, including hyperthermia, oxygen radicals, heavy metals, ethanol, and amino acid analogues. In addition, the heat shock response is induced during clinically relevant situations such as ischemia/reperfusion and circulatory and hemorrhagic shock. All of the above stresses have in common that they disturb the tertiary structure of proteins and have adverse effects on cellular metabolism. Pretreatment of cells with a mild stress, sufficient to induce the expression of hsps, results in protection to subsequent insults. This phenomenon has been coined "stress tolerance" and is apparently caused by the resolubilization of proteins that were denatured during the stress. In addition, cellular structures (microfilaments and centrosomes) and processes (transcription, splicing, and translation) are stabilized or repaired during a second stress in stress tolerant cells and organisms. There is a great body of evidence indicating a direct role of hsps in the stabilization of these events. The intrinsic capacity of hsps to protect cells has potential relevance as a natural mechanism of organ protection during harmful environmental conditions and operative procedures, and in the combat against pathogens.

Animals↗

PubMed1999

Expression of HSP70 is impaired at the transcriptional level in stressed murine neuroblastoma cells.

Although the expression of heat shock or stress proteins (hsps) is a well conserved response to stress, the accumulation of these proteins is different between various cell-types. Particularly, cells of neuronal origin show a reduced expression of Hsp70 after stress. The possible mechanism of this reduced Hsp70 expression was studied in thermally stressed murine neuroblastoma cells (N18). These cells showed no detectable levels of Hsp70 or Hsp70 mRNA after heat shock. Hsp70 transcription was not detectable after stress. However, heat shock transcription factor 1 (HSF1) is active in these cells under stress conditions. Cells transiently transfected with the chloramphenicol acetyltransferase (CAT) gene under control of the human heat shock promoter showed a stress-dependent expression of CAT, suggesting that the cells contain the factors necessary for the expression of Hsp70. Integration of the foreign human heat shock promoter into genomic DNA did not affect its transcriptional inducibility. These results suggest that the impairment of Hsp70 expression in N18 cells is due to the environment (chromatin structure, methylation pattern) of the Hsp70 locus.

Animals↗