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At least 127 records · Page 7Linked to original sources
PubMed2003

Comparison of nodule induction in legume and actinorhizal symbioses: the induction of actinorhizal nodules does not involve ENOD40.

Two types of root nodule symbioses are known for higher plants, legume and actinorhizal symbioses. In legume symbioses, bacterial signal factors induce the expression of ENOD40 genes. We isolated an ENOD40 promoter from an actinorhizal plant, Casuarina glauca, and compared its expression pattern in a legume (Lotus japonicus) and an actinorhizal plant (Allocasuarina verticillata) with that of an ENOD40 promoter from the legume soybean (GmENOD40-2). In the actinorhizal Allocasuarina sp., CgENOD40-GUS and GmENOD40-2-GUS showed similar expression patterns in both vegetative and symbiotic development, and neither promoter was active during nodule induction. The nonsymbiotic expression pattern of CgENOD40-GUS in the legume genus Lotus resembled the nonsymbiotic expression patterns of legume ENOD40 genes; however, in contrast to GmENOD40-2-GUS, CgENOD40-GUS was not active during nodule induction. The fact that only legume, not actinorhizal, ENOD40 genes are induced during legume nodule induction can be linked to the phloem unloading mechanisms established in the zones of nodule induction in the roots of both types of host plants.

Base Sequence↗
PubMed2000

Quadruple tacrolimus-based induction therapy including azathioprine and ALG does not significantly improve outcome after liver transplantation when compared with standard induction with tacrolimus and steroids: results of a prospective, randomized trial.

BACKGROUND: Tacrolimus in combination with prednisolone has been proven to be a safe and effective immunosuppressive induction therapy in solid organ transplantation. However, it remains unclear whether a tacrolimus-based quadruple induction regimen with azathioprine and an antilymphocytic preparation could further improve the results after orthotopic liver transplantation. Therefore, we designed a prospective, randomized study to compare the immunosuppressive efficacy of dual (tacrolimus and prednisolone) and quadruple (tacrolimus, azathioprine, ALG Merieux and prednisolone) induction after liver transplantation. METHODS: After randomization, 120 consecutive patients of primary liver transplants were divided into the dual group (n=59) and the quadruple group (n=61) and followed for a minimum of 3 years. RESULTS: Patient survival at 3 years was 88.2% in the dual versus 94.9% in the quadruple group. Overall 25 patients in each group (41 and 42%, respectively) developed acute rejection. There was no difference in the number and severity of rejections. In each group only four patients required OKT3-therapy, however, although three of four patients in the quadruple group responded to OKT3 and cleared rejection, none of the four patients in the dual group were treated successfully with OKT3 (P<0.02). Rejection in these patients resolved only after additional treatment with mycophenolate mofetil. Adverse events and infections were equally distributed in both groups. Asymptomatic Cytomegalovirus infections were more common in the quadruple group (P<0.02). As of today, only one patient developed posttransplant lymphoproliferative disease (dual group). CONCLUSIONS: The data from our single-center study indicate that both tacrolimus-based dual and quadruple immunosuppressive induction regimens yield similar safety and effectiveness after liver transplantation.

Adult↗
PubMed2000

Differential effects of cyclosporine A, methylprednisolone, mycophenolate, and rapamycin on CD154 induction and requirement for NFkappaB: implications for tolerance induction.

BACKGROUND: Recent experimental data indicate that the targeting of the costimulatory molecule CD40-ligand (CD154) may well offer an opportunity for tolerance induction in transplant recipients and patients with autoimmune diseases, although the optimal therapeutic strategy for clinical application of CD154 monoclonal antibody (mAb) is unclear. METHODS: We undertook vascularized heterotopic cardiac allograft transplantation in completely MHC-mismatched mice, treated recipients with CD154 mAb plus various immunosuppressive agents, and performed flow cytometric analysis of CD154 expression by T cells activated in vitro in the presence of corresponding immunosuppressive agents. We also tested the extent to which CD154 induction was NFkappaB-dependent by using NFkappaB/p50-deficient mice as allograft recipients and as source of cells for in vitro studies of CD154 induction, and through use of proteasome inhibitors to block IkappaBalpha degradation and NFKB activation in wild-type mice. RESULTS: Concomitant use of cyclosporin A or methylprednisolone, but not rapamycin or mycophenolate, inhibited CD154 mAb-induced allograft survival. The differential effects of these agents on CD154 mAb-induced tolerance correlated with their capacity to inhibit activation-induced CD154 expression on CD4+ T cells. Full expression of CD154 expression was found to require NF-kappaB activation, and CD154 mAb was ineffective in NF-kappaB/p50 deficient allograft recipients or control mice in which NF-kappaB activation was blocked by proteasome inhibition. CONCLUSIONS: Strategies to use CD154 mAb clinically must take into account the effects of immunosuppressive agents on CD154 induction, which seems to be at least partially NF-kappaB dependent. Our data suggest that ligation of surface-expressed CD154 provides an important signal that modulates T cell activation and thereby contributes to the effects of CD154 mAb, in addition to previously recognized actions involving blockade of CD40/CD154-dependent cell activation and activation-induced cell death.

Animals↗
PubMed1996

Ventricular fibrillation induction using nonsynchronized low energy external shock during rapid ventricular pacing: method of induction when fibrillation mode of ICD fails.

Third-generation implantable cardioverter defibrillators (ICD) are frequently implanted with nonthoracotomy systems and provide noninvasive methods for electrical stimulation and ventricular fibrillation induction. These modalities facilitate postoperative testing of the ICD. Rapid right ventricular burst pacing via the defibrillator is commonly used for initiation of ventricular tachyarrhythmias. However, with the available third-generation devices, ventricular fibrillation (VF) induction may be impossible in up to 19% of the patients. In these cases, transvenous placement of a right ventricular catheter has been required to generate VF and appropriately evaluate the device. We report a new technique of noninvasive induction of VF using a low energy external nonsynchronized shock delivered during ICD fibrillation induction pacing. In three patients, after all efforts to induce VF by the Ventritex Cadence V-100 had failed, a 20 J nonsynchronized shock was delivered during rapid RV pacing. This resulted in VF on the first attempt in all patients. This noninvasive technique of VF initiation may provide a useful clinical approach to ICD testing that eliminates the costs and risks of an invasive procedure.

Adult↗
PubMed2005

Alemtuzumab induction and prednisone-free maintenance immunotherapy in kidney transplantation: comparison with basiliximab induction--long-term results.

This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.

Adolescent↗
PubMed1985

Induction of the chloramphenicol acetyltransferase gene cat-86 through the action of the ribosomal antibiotic amicetin: involvement of a Bacillus subtilis ribosomal component in cat induction.

The plasmid gene cat-86 and the cat gene resident on pC194 each encode chloramphenicol-inducible chloramphenicol acetyltransferase activity in Bacillus subtilis. Chloramphenicol induction has been proposed to result from chloramphenicol binding to ribosomes, which then permits the drug-modified ribosomes to perform events essential to induction. If this proposal were correct, B. subtilis mutants containing chloramphenicol-insensitive ribosomes should not permit chloramphenicol induction of either cat-86 or pC194 cat. However, we and others have been unable to isolate chloramphenicol-resistant ribosomal mutants of B. subtilis 168. We therefore developed a simple procedure for screening other antibiotics for the potential to induce cat-86 expression. One antibiotic, amicetin, was found to be an effective inducer of cat-86 but not of the cat gene on pC194. Amicetin and chloramphenicol each interact with the 50S ribosomal subunit, and the mechanism of cat-86 induction by both drugs may be similar. Amicetin-resistant mutants of B. subtilis were readily isolated, and in none of six mutants tested was cat-86 detectably inducible by amicetin, although the chloramphenicol-inducible phenotype was retained. The ami-1 mutation which is present in one of these amicetin-resistant mutants was mapped by PBS1 transduction to the "ribosomal gene cluster" adjacent to cysA. Additionally, ribosomes from cells harboring the ami-1 mutation contained an altered BL12a protein, as detected in two-dimensional polyacrylamide gel electrophoresis. Lastly, an in vitro protein-synthesizing system that uses ribosomes from an ami-1-containing cell line was more resistant to amicetin than a system that uses ribosomes from an amicetin-sensitive but otherwise isogenic strain. These results indicate that the host mutation, ami-1, which effectively abolished the inducibility of cat-86 by amicetin, altered a ribosomal component.

Acetyltransferases↗
PubMed1990

Induction of bovine papillomavirus E2 gene expression and early region transcription by cell growth arrest: correlation with viral DNA amplification and evidence for differential promoter induction.

The bovine papillomavirus type 1 (BPV-1) genome replicates as a latent plasmid in mouse C127 cells transformed in vitro by the virus. However, we have recently shown that BPV-1 DNA amplification can be induced in a subpopulation of cells under culture conditions which suppress cell proliferation, a finding which led us to hypothesize that expression of a viral replication factor was regulated by cell growth stage. In this report, we describe the detection in these cells of abundant BPV-1 nuclear E2 antigen by immunofluorescence analysis. Expression of E2 antigen in fibropapilloma tissue was similarly localized to nonproliferating epidermal cells of the lower spinous layers--the natural site of induction of vegetative viral DNA replication. Immunoprecipitation analysis showed that the previously characterized 48-kilodalton (transactivator) and 31-kilodalton (repressor) E2 proteins were both induced in growth-arrested cell cultures. In parallel with E2 antigen synthesis under conditions of serum-deprivation in vitro, we observed a significant increase in levels of BPV-1 early region mRNAs. Furthermore, we present evidence for preferential induction of the P2443 promoter, in addition to specific induction of the P7940 promoter in response to serum deprivation. These observations indicate a central role for E2 transcription factors in the induction of viral DNA amplification in division-arrested cells in vitro and in vivo and suggest that this process is associated with a qualitative switch in the expression of viral early region genes.

Animals↗
PubMed1992

Induction of polyomavirus DNA replication by carcinogens in polyomavirus-transformed rat cells: evidence that the viral enhancer is not the primary target in the induction pathway.

In the polyomavirus (Py)-transformed rat cell line designated LPT, replication of the integrated Py DNA can be induced by exposure of the cells to carcinogens. In view of the observation that enhancer elements are essential components of the Py origin of replication, it appeared plausible that the induction is triggered by synthesis or modification of an enhancer-binding protein which is required for activation of the viral origin. To test this hypothesis, we have used a plasmid containing a modified Py origin (test plasmid), in which the Py enhancer has been replaced with five repeats of the yeast GAL4 upstream activating sequence, and a plasmid encoding the GAL4 transcriptional activator protein. Previous studies in which these two plasmids were cotransfected into mouse cells that are permissive for Py showed that the GAL4 protein can transactivate the modified Py origin and cause replication of the test plasmid. When similar cotransfection assays were performed in LPT cells, no replication of the test plasmid was observed unless the cells were exposed to the carcinogen mitomycin C subsequent to the transfection, in which case replication of the test plasmid was induced. Control experiments showed that even though the GAL4 protein was required for the induction, its concentration was not affected by the exposure to mitomycin C. These results indicate that the primary target in the induction pathway is not an enhancer-binding protein; instead, the induction appears to be triggered by changes in other components of the replication initiation complex which may be associated with the origin core.

Animals↗
PubMed1996

Induction of susceptibility to tumor necrosis factor by E1A is dependent on binding to either p300 or p105-Rb and induction of DNA synthesis.

The introduction of the adenovirus early region 1A (E1A) gene products into normal cells sensitizes these cells to the cytotoxic effects of tumor necrosis factor (TNF). Previous studies have shown that the region of E1A responsible for susceptibility is CR1, a conserved region within E1A which binds the cellular proteins p300 and p105-Rb at nonoverlapping sites. Binding of these and other cellular proteins by E1A results in the induction of E1A-associated activities such as transformation, immortalization, DNA synthesis, and apoptosis. To investigate the mechanism by which E1A induces susceptibility to TNF, the NIH 3T3 mouse fibroblast cell line was infected with viruses containing mutations within E1A which abrogate binding of some or all of the cellular proteins to E1A. The results show that TNF susceptibility is induced by E1A binding to either p300 or p105-Rb. E1A mutants that bind neither p300 nor p105-Rb do not induce susceptibility to TNF. Experiments with stable cell lines created by transfection with either wild-type or mutant E1A lead to these same conclusions. In addition, a correlation between induction of DNA synthesis and induction of TNF sensitivity is seen. Only viruses which induce DNA synthesis can induce TNF sensitivity. Those viruses which do not induce DNA synthesis also do not induce TNF sensitivity. These data suggest that the mechanisms underlying induction of susceptibility to TNF by E1A are intimately connected to E1A's capacity to override cell cycle controls.

3T3 Cells↗
PubMed1998

Reovirus induction of and sensitivity to beta interferon in cardiac myocyte cultures correlate with induction of myocarditis and are determined by viral core proteins.

Reovirus-induced acute myocarditis in mice serves as a model to investigate non-immune-mediated mechanisms of viral myocarditis. We have used primary cardiac myocyte cultures infected with a large panel of myocarditic and nonmyocarditic reassortant reoviruses to identify determinants of viral myocarditic potential. Here, we report that while both myocarditic and nonmyocarditic reoviruses kill cardiac myocytes, viral myocarditic potential correlates with viral spread through cardiac myocyte cultures and with cumulative cell death. To address the role of secreted interferon (IFN), we added anti-IFN-alpha/beta antibody to infected cardiac myocyte cultures. Antibody benefited nonmyocarditic more than myocarditic virus spread (P < 0.001), and this benefit was associated with the reovirus M1 and L2 genes. There was no benefit for a differentiated skeletal muscle cell line culture (C2C12 cells), suggesting cell type specificity. IFN-beta induction in reovirus-infected cardiac myocyte cultures correlated with viral myocarditic potential (P = 0.006) and was associated with the reovirus M1, S2, and L2 genes. Sensitivity to the antiviral effects of IFN-alpha/beta added to cardiac myocyte cultures also correlated with viral myocarditic potential (P = 0.004) and was associated with the same reovirus genes. Several reoviruses induced IFN-beta levels discordant with their myocarditic phenotypes, and for those tested, sensitivity to IFN-alpha/beta compensated for the anomalous induction levels. Thus, the combination of induction of and sensitivity to IFN-alpha/beta is a determinant of reovirus myocarditic potential. Finally, a nonmyocarditic reovirus induced cardiac lesions in mice depleted of IFN-alpha/beta, demonstrating that IFN-alpha/beta is a determinant of reovirus-induced myocarditis. This provides the first identification of reovirus genes associated with IFN induction and sensitivity and provides the first evidence that IFN-beta can be a determinant of viral myocarditis and reovirus disease.

Animals↗
PubMed1993

Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers.

Retinoic acid (RA) treatment of human embryonal carcinoma (EC) NTera-2 (NT2) cells induces expression of major histocompatibility complex (MHC) class I and beta-2 microglobulin surface molecules. We found that this induction was accompanied by increased levels of MHC class I mRNA, which was attributable to the activation of the two conserved upstream enhancers, region I (NF-kappa B like) and region II. This activation coincided with the induction of nuclear factor binding activities specific for the two enhancers. Region I binding activity was not present in undifferentiated NT2 cells, but binding of an NF-kappa B heterodimer, p50-p65, was induced following RA treatment. The p50-p65 heterodimer was produced as a result of de novo induction of p50 and p65 mRNAs. Region II binding activity was present in undifferentiated cells at low levels but was greatly augmented by RA treatment because of activation of a nuclear hormone receptor heterodimer composed of the retinoid X receptor (RXR beta) and the RA receptor (RAR beta). The RXR beta-RAR beta heterodimer also bound RA responsive elements present in other genes which are likely to be involved in RA triggering of EC cell differentiation. Furthermore, transfection of p50 and p65 into undifferentiated NT2 cells synergistically activated region I-dependent MHC class I reporter activity. A similar increase in MHC class I reporter activity was demonstrated by cotransfection of RXR beta and RAR beta. These data show that following RA treatment, heterodimers of two transcription factor families are induced to bind to the MHC enhancers, which at least partly accounts for RA induction of MHC class I expression in NT2 EC cells.

Animals↗
PubMed2003

Tolerance induction to a mammalian blood group-like carbohydrate antigen by syngeneic lymphocytes expressing the antigen, II: tolerance induction on memory B cells.

Induction of immune tolerance on memory B cells specific to transplantation carbohydrate antigens was studied in the experimental animal model of alpha1,3galactosyltransferase knockout (KO) mice, which lack the alpha-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) and can produce the anti-Gal antibody against it. Memory anti-Gal B cells were generated by immunization of KO mice with pig kidney membranes (ie, xenogeneic cell membranes expressing an abundance of alpha-gal epitopes). Lymphocytes including memory anti-Gal B cells were administered into lethally irradiated KO mice, together with syngeneic wild-type (WT) lymphocytes expressing alpha-gal epitopes. Memory anti-Gal B cells were completely tolerized after being in vivo for 14 days with WT lymphocytes. This was indicated by the lack of anti-Gal immunoglobulin G (IgG) response following immunization with pig kidney membranes vs the extensive anti-Gal response in mice that did not receive WT lymphocytes. Tolerance induction was prevented if T cells were activated by alloantigens. This tolerance was highly specific to anti-Gal B cells and did not affect memory B cells with closely related specificity, such as B cells with anti-blood group A specificity. Tolerance induction on anti-Gal B cells was found to be time dependent and required more than 10 days of in vivo exposure of these B cells to WT lymphocytes. These observations suggest a novel method for induction of tolerance to transplantation carbohydrate antigens in humans, by in vitro transduction of autologous blood lymphocytes with an adenovirus containing the corresponding glycosyltransferase gene and administration of the transduced cells into the circulation after removal of natural antibodies to the antigen.

ABO Blood-Group System↗
PubMed2006

Desflurane anesthesia after sevoflurane inhaled induction reduces severity of emergence agitation in children undergoing minor ear-nose-throat surgery compared with sevoflurane induction and maintenance.

Emergence agitation may occur after general anesthesia with volatile anesthetics in children. We designed this study to examine the emergence behavior of children undergoing ear-nose-throat surgery after sevoflurane induction and desflurane maintenance versus both sevoflurane induction and maintenance using a recently published Pediatric Anesthesia Emergence Delirium (PAED) scale. In 38 premedicated children aged 12 mo to 7 yr mask induction with sevoflurane was performed and they were randomly assigned to receive either sevoflurane (n = 19) or desflurane (n = 19) for maintenance of general anesthesia. Time to tracheal extubation, modified Aldrete score, emergence behavior, recovery complications, and pain scores were assessed. The PAED scale showed a significant advantage for desflurane (6 [0-15] versus 12 [2-20], maximum total score of 20 for severe agitation). Time to extubation was significantly shorter with desflurane than with sevoflurane (5.4 +/- 1.4 versus 13.4 +/- 1.8 min). The modified Aldrete score on arrival in the postanesthesia care unit (PACU) was significantly lower in children receiving sevoflurane for maintenance. Time to discharge from PACU to normal ward and the incidence of adverse effects were not significantly different between the groups. In conclusion, the use of desflurane for maintenance of anesthesia after sevoflurane induction in children is associated with less severe emergence agitation and faster emergence times.

Anesthesia Recovery Period↗
PubMed1975

Induction of rho- mutants in Saccharomyces cerevisiae by guanidine hydrochloride. II. Conditions that prevent rho- induction.

The induction of rho- "petite" mutants by guanidine hydrochloride (GuHCl) is inhibited in several conditions. Anaerobiosis inhibited the induction either with or without cell multiplication. Both nalidixic acid (NA) and cycloheximide (CH) inhibited the induction of mutants. On the other hand, chloramphenicol (CAP) produced a dual effect: at low concentration it stimulated, at high concentration it inhibited, the induction. The effect of these different inhibitors on the transformation of rho+ mother cells into rho- by GuHCl is discussed.

Anaerobiosis↗
PubMed1993

Cerebral arterial blood flow velocity during induction of general anesthesia: rapid intravenous induction versus awake intubation.

Changes in middle cerebral arterial flow velocity (MCAV) during rapid intravenous induction and awake intubation using transcranial Doppler sonography were investigated. The study involved 20 patients without disorders of the central nervous or cardiovascular systems who were scheduled for maxillofacial surgery. In the intravenous induction group, anesthesia was induced with sodium thiopental, and orotracheal or nasotracheal intubation was facilitated with succinylcholine chloride or alcuronium chloride. In the awake intubation group, orotracheal or nasotracheal intubation was performed under intravenous sedation with diazepam and topical anesthesia with 4% lidocaine. Arterial blood pressures, heart rate, and MCAV were monitored at specific intervals. During intravenous induction, blood pressures decreased after the administration of thiopental and muscle relaxants and increased during endotracheal intubation. MCAV was remarkably slowed after the administration of thiopental and during mask ventilation. During awake intubation, blood pressures were increased by endotracheal intubation. MCAV was decreased from the administration of diazepam to the transtracheal injection of lidocaine, but returned to the control value from endotracheal spray to endotracheal intubation. These results suggest that smooth awake intubation may be the safest method of induction for patients with cerebrovascular disorders.

Alcuronium↗
PubMed1997

p53-dependent p21 induction following gamma-irradiation without concomitant p53 induction in a human peripheral neuroepithelioma cell line.

We previously generated cell hybrids between a derivative of the E6-containing HeLa cell line and a p53 null peripheral neuroepithelioma (PNET) cell line. Although p53 protein from the hybrids was genotypically wild type, it did not demonstrate wild-type behavior. Therefore, in the present study, we introduced wild-type p53 into the PNET parent to investigate whether p53 retained wild-type function within this cell line. Although the p53 null PNET parent lacked detectable p21 protein, introduction of wild-type p53 resulted in a detectable expression of p21 protein in all clones tested, suggestive of wild-type p53 function. In addition, p53 expression was necessary for induction of p21 in response to irradiation, and, furthermore, we show this induction to occur at the transcriptional level. Although introduction of wild-type p53 seems to be responsible for p21 induction, the overall protein levels of p53 were not induced. The involvement of p53 in up-regulating p21 is further substantiated by the observation that p21 up-regulation was dependent on the introduction of the wild-type protein. Our results suggest that wild-type p53 is capable of up-regulating p21 in response to DNA damage in the absence of p53 induction.

Biological Transport↗
PubMed1988

Differential induction of rat hepatic glutathione S-transferase isoenzymes by hexachlorobenzene and benzyl isothiocyanate. Comparison with induction by phenobarbital and 3-methylcholanthrene.

Male Wistar rats were treated with hexachlorobenzene, benzyl isothiocyanate, phenobarbital or 3-methylcholanthrene. Hepatic cytosolic glutathione S-transferase (GST) activity was determined with the substrates 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, ethacrynic acid and trans-4-phenyl-3-buten-2-one. Cytosolic glutathione peroxidase activity was measured with cumene hydroperoxide. GST activity toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and ethacrynic acid was enhanced by all compounds, hexachlorobenzene and 3-methylcholanthrene causing the largest and the smallest increase respectively. Trans-4-phenyl-3-buten-2-one-conjugating activity exhibited only small changes, while peroxidase activity with cumeme hydroperoxide was not changed by any of the inducing agents. GST isoenzymes were purified on S-hexylglutathione Sepharose 6B and separated by means of FPLC-chromatofocusing, to evaluate effects on the GST isoenzyme pattern. Hexachlorobenzene and phenobarbital both caused an increase in the relative amounts of subunits 1 and 3 when compared with subunits 2 and 4 respectively. For 3-methylcholanthrene only induction of subunit 1 was observed, possibly due to the relatively low induction levels of total GST activity. In benzyl isothiocyanate-treated animals, an induction of subunit 3 was found as well as an increase in the relative amount of subunit 2. Thus, benzyl isothiocyanate behaves differently from hexachlorobenzene, phenobarbital and 3-methylcholanthrene as an inducing agent of rat hepatic glutathione S-transferases.

Animals↗
PubMed1992

Induction of a pleiotropic response by phenobarbital and related compounds. Response in various inbred strains of rats, response in various species and the induction of aldehyde dehydrogenase in Copenhagen rats.

The ability of phenobarbital (PB) to induce a "pleiotropic response" which includes both cytochromes P450 (CYP) as well as other drug-metabolizing enzymes was investigated in mice, rabbits, hamsters, and various inbred strains of rats. PB induced similar drug-metabolizing enzymes (CYP2B, CYP3A, and epoxide hydrolase) in rats, mice, rabbits and hamsters. PB and two structural analogues (ethylphenylhydantoin and barbital) induced a variety of drug-metabolizing enzymes (CYP2B, CYP3A, CYP2A, epoxide hydrolase) in a series of inbred strains of rats. In contrast, levels of aldehyde dehydrogenase (ALDH) (propionaldehyde, NAD+) which were expressed constitutively in all strains of rats were induced by PB in only two of the eight strains (ACI, Copenhagen). Further investigations of ALDH induction by structurally diverse compounds in Copenhagen rats demonstrated a strong correlation between the induction of ALDH and other elements of the pleiotropic response (CYP2B, CYP3A, epoxide hydrolase). These results imply that induction of ALDH (propionaldehyde, NAD+) is associated with the PB pleiotropic response in Copenhagen rats.

Aldehyde Dehydrogenase↗