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Volume 133 (2003)
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Volume 133, Issue 6
Displaying 1-16 of 16 articles from this issue
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Tomoko Kaneko-Ishino, Takashi Kohda, Fumitoshi Ishino2003 Volume 133 Issue 6 Pages 699-711
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSGenomic imprinting is a system of non-Mendelian inheritance that is unique to mammals. Two types of imprinted genes show parent-of-origin-specific expression patterns: the paternally expressed genes (Pegs), and the maternally expressed genes (Megs). Parental genomic imprinting memory is maintained in the somatic cell lineage and regulates the expression of Pegs and Megs, while it is erased and re-established in the germ cell lineage according to the sex of the individual. The paternal and maternal imprinting mechanisms, which regulate different sets of Pegs and Megs, are essential for establishing the parental expression profiles of imprinted genes that are observed in sperms and eggs. Based on recent evidence, we outline the relationship between parental imprinting and the expression profiles of Pegs and Megs and discuss a novel view of the regulation of genomic imprinting. We also discuss the biological significance of genomic imprinting and propose hypotheses on the essential nature of genomic imprinting and the close relationship between genomic imprinting and the acquisition of placental tissues during mammalian evolution.View full abstractDownload PDF (7452K) -
Yujun Di, Jinjun Li, Yu Zhang, Xianghuo He, Hong Lu, Dongbin Xu, Jiqia ...2003 Volume 133 Issue 6 Pages 713-718
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSThe gene HCAP1 (HCC-associated Protein 1), one variant of GEMIN4, has been mapped in a minimum LOH region on chromosome 17p13.3 and encodes a 1047-amino acid protein. Function predictions based on the amino acid sequence of protein HCAP1 revealed it to contain one helix-loop-helix motif and one leucine zipper domain. Using yeast two-hybrid screening, five zinc-finger proteins were identified as HCAP1-interacting proteins. Among them, NDP52 (nuclear dot protein 52) appeared most frequently in positive clones and was the most strongly interacting protein. Then, the interaction between HCAP1 and NDP52 was confirmed by GST pull-down assay and a coimmunoprecipitation experiment. Moreover, an immunofluorescent staining assay indicated that NDP52 colocalizes with HCAP1 in the cytoplasm. By deletion analysis, the leucine zipper domain of HCAP1 and the zinc finger domain of NDP52 were identified as important regions responsible for the interaction.View full abstractDownload PDF (2423K) -
Satoru Yamagishi, Masashi Yamada, Hisatsugu Koshimizu, Satomi Takai, H ...2003 Volume 133 Issue 6 Pages 719-724
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSPreviously, we reported that p38, which belongs to the mitogen-activated protein kinase (MAPK) superfamily, has an important role in the induction of apoptosis of cultured cerebellar granule neurons. However, the molecular mechanisms upstream of p38 activation remain unclear. Apoptosis signal-regulating kinase-1 (ASK1), a MAPK kinase kinase (MAPKKK) protein, is known to activate both c-Jun N-terminal kinase (JNK) and p38 via MAPK kinase (MKK) 4/7 and MKK3/6, respectively. Here, we examined whether ASK1 is involved in the activation of p38 in the low potassium (LK)-induced apoptosis of cerebellar granule neurons. We found that ASK1 was activated after a change to LK medium. In addition, the expression of ASK1-KM, a domi-nant-negative form of ASK1, using an adenovirus system was found to inhibit the acti-vation of p38 and c-Jun and to prevent apoptosis. On the other hand, the expression of ASK1-ΔN, a constitutively active form of ASK1, activated p38 and c-Jun, but not JNK, another possible downstream target of ASK1. Furthermore, we examined the relationship between phosphatidylinositol 3-kinase (PI3-K) and ASK1. The addition of LY294002, a specific inhibitor of PI3-K, enhanced the ASK1 activity. These results indicate that ASK1 works downstream of PI3-K to regulate the p38-c-Jun pathway and apoptosis in cultured cerebellar granule neurons.View full abstractDownload PDF (2873K) -
Andrew J. Nok, Emmanuel O. Balogun2003 Volume 133 Issue 6 Pages 725-730
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSThe release of Sialic acid (SA) into the serum by Trypanosoma congolense infected BalbC mice was investigated. A progressive increase in the level of serum SA corre-sponding to anemia and parasitemia was observed. At maximum parasitemia, the level of total SA from the red blood cells (RBC) dropped by about 45%. Solved polyno-mials revealed an association between free serum SA and RBC-SA. Positive roots of quadratics were used to predict complete cleavage of RBC-SA on day 7.01 and maximum accumulation of free serum SA on day 6.6. A steady rise in the level of serum sialidase (SD) activity and a low packed cell volume (PCV) with an increase in para-sitemia were observed. Mice infused with galactose, methyl-β-gal, lactose, mannose, or L-arabinose and challenged by intraperitoneal inoculation with Trypanosoma congolense neither developed anemia nor secreted free SA above the control level even though there was detectable SD activity. Bloodstream Trypanosoma congolense para-sites were isolated using DEAE cellulose from heparinized blood of experimentally infected BalbC mice. The parasites were lysed with 0.2% Triton-CF 54 to release mem-brane bound SD. The activity of the SD was proportional to the number of parasites. The enzyme was partially purified on Q-Sepharose and Fetuin agarose columns suc-cessively. The final active fraction from the latter column was used as the partially purified SD. The enzyme had an optimum pH of 6 and was maximally active at 37°C with a requirement for the divalent ions Ca2+ and Mg2+. The enzyme was highly spe-cific for NeuAc5α2, 3 lac and Methylumbelliferyl-Neu5Ac (4-MU-Neu5Ac) with KM values of 0.34 and 0.025mM, respectively. It was inhibited competitively by 2, 3-didehy-droneuraminic acid (Neu5Ac2en) and para-nitro-phenyloxamic acid (pNPO) with inhibition binding constants Ki of 65 and 215 μM, respectively. In deviation from the procyclic trypanosomal SD, it lacked trans-sialidase (TS) activity. The possible role of a secreted bloodstream Trypanosoma congolense SD and the development of anemia in the pathogensesis of trypanosomiasis are discussed.View full abstractDownload PDF (790K) -
Masayo Gozu, Young Ho Lee, Yumiko Ohhashi, Masaru Hoshino, Hironobu Na ...2003 Volume 133 Issue 6 Pages 731-736
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSAlthough native β2-microglobulin (β2-m), the light chain of the major histocompatibility complex class I antigen, assumes an immunoglobulin domain fold, it is also found as a major component of dialysis-related amyloid fibrils. In the amyloid fibrils, the conformation of β2-m is considered to be largely different from that of the native state, and a monomeric denatured form is likely to be a precursor to the amyloid fibril. To obtain insight into the conformational dynamics of β2-m leading to the for-mation of amyloid fibrils, we studied the reduction and reoxidation of the disulfide bond by reduced and oxidized dithiothreitol, respectively, and the effects on the reduction of the chaperonin GroEL, a model protein that might destabilize the native state of β2-m. We show that β2-m occasionally unfolds into a denatured form even under physiological conditions and that this transition is promoted upon interaction with GroEL. The results imply that in vivo interactions of β2-m with other proteins or membrane components could destabilize its native structure, thus stabilizing the amyloid precursor.View full abstractDownload PDF (763K) -
Isao Suetake, Junko Miyazaki, Chikako Murkami, Hideyuki Takeshima, Sho ...2003 Volume 133 Issue 6 Pages 737-744
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSRecombinant mouse Dnmt3a and Dnmt3b were expressed in sf9 cells and purified to near homogeneity. The purified Dnmt3a and Dnmt3b gave specific activities of 1.8 ± 0.3 and 1.3 ± 0.1 mol/h/mol enzyme towards poly(dGdC)-poly(dGdC), respectively, which were the highest among those reported. Dnmt3a or Dnmt3b showed similar Km values towards poly(dIdC)-poly(dIdC) and poly(dGdC)-poly(dGdC). The Km values for S-adenosyl-L-methionine were not affected by the methyl-group acceptors, poly(dI-dC)-poly(dIdC) and poly(dG-dC)-poly(dGdC). The results indicate that the enzymes are de novo-type DNA methyltransferases. Dnmt3a and Dnmt3b activities were inhibited by Mn2+ and Ni2+ and showed broad pH optima around neutral pH. Both enzymes were susceptible to sodium ions, which inhibited their activity at around physiological ionic strength. However, Dnmt3a was fully active at physiological potassium con-centration, but Dnmt3b was not. Using designed oligonucleotides for the analysis of cytosine methylation, we demonstrated that, in addition to CpG, Dnmt3a methylated CpA but not CpT and CpC, and that Dnmt3b methylated CpA and CpT but scarcely CpC. The relative activity of Dnmt3b towards nonCpG sequences was higher than that of Dnmt3a. These differences in enzymatic properties of Dnmt3a and Dnmt3b may contribute to the distinct functions of these enzymes in vivo.View full abstractDownload PDF (1919K) -
Karine Sudre, Christine Leroux, Geneviève Piétu, Isabell ...2003 Volume 133 Issue 6 Pages 745-756
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSMacro-arrays, on which 1339 human skeletal muscle cDNA clone inserts had been spotted as PCR products, were used to make large-scale measurement of gene expression in bovine muscles during ontogenesis. Ten complex cDNA targets derived from two mixed muscle samples, Rectus abdominis (rather red oxidative muscle, RA) and Semitendinosus (rather white glycolytic muscle, ST), were taken from foetuses at 4 different stages (110, 180, 210, and 260 days post-conception) and from 15-month-old young bulls to generate differential expression patterns. Each sample analysed was prepared from a pool of RNA extracted from muscle tissues sampled from at least 6 different animals. Approximately 200 expression signals were validated and taken into account to provide a first “bovine” muscle gene repertoire. Despite the relatively small number of probes and the heterologous approach, this made it possible to iden-tify up to 7 genes differentially expressed between RA and ST, depending on age. From 110 days post-conception to 15 months of age, differences in the expression lev-els of 110 genes were detected in the four comparisons between two consecutive ages. By comparing 260 days post-conception foetal muscles and adult muscles, up to 87 genes were overexpressed, whereas only 7 genes were shown to be down-regulated. Among these genes, 33% have unknown biological functions. Taken together, the results reported here underline the importance of the last three months of gestation in muscle myogenesis, and highlight new genes involved in this process.View full abstractDownload PDF (3993K) -
M. Caraglia, M. Marra, G. Giuberti, A. M. D'Alessandro, A. Baldi, P. T ...2003 Volume 133 Issue 6 Pages 757-765
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSInterferon-α (IFNα) can induce apoptosis, a process regulated by a complex network of cell factors. Among these, eukaryotic initiation factor-5A (eIF-5A) is peculiar because its activity is modulated by the post-translational formation of the amino acid hypusine. Here we report the effects of IFNα and epidermal growth factor (EGF) on apoptosis and eIF-5A activity in human epidermoid oropharyngeal KB and lung H1355 cancer cells. We found that 48-h exposure to 1, 000 and 2, 000 IU/ml IFNα induced about 50% growth inhibition and apoptosis in H1355 and KB cells, respectively, and the addition of EGF completely antagonized this effect. When IFNα induced apoptosis, a hyperactivation of MEK-1 and ERK signalling and a decrease of the hypusine-containing form and, thus, of eIF-5A activity were recorded. The latter effect was again antagonized by the addition of EGF to IFNα-pretreated cells, probably through the activation of the EGF→ERK-dependent pathway, since the addition of the specific MEK-1 inhibitor PD098059 abrogated the recovery of intracellular hypusine content induced by EGF in IFNα-pretreated cancer cells. Subsequently, we evaluated if the hypusine synthesis inhibitor (and eIF-5A inactivator) N1-guanyl-1, 7-diaminoheptane (GC7) synergized with IFNα in the induction of cell growth inhibition and apoptosis. The analysis of the isobologram of IFNα and GC7 demonstrated a strong synergism between the two drugs in inducing cell growth inhibition. We also found that GC7 and IFNα had a synergistic effect on apoptosis. These data suggest that the apoptosis induced by IFNα could be regulated by eIF-5A that, therefore, could represent a useful target for the potentiation of IFNα antitumor activity.View full abstractDownload PDF (3936K) -
Atsushi Shimizu, Tatsuya Samejima, Shun Hirota, Shotaro Yamaguchi, Nob ...2003 Volume 133 Issue 6 Pages 767-772
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSType III Cu ligand, His456 and His458, of Myrothecium verrucaria (MT-1) bilirubin oxidases (BO) [EC 1.3.3.5] were doubly mutated as to Lys, Asp, and Val. In spite of pertur-bation of the type III Cu centers, these mutants were pale blue or colourless when isolated. However, they became intense blue on reaction with reducing agents such as dithionite, ascorbate, hexacyanoferrate(II), and octacyanotangstate(IV) under air, or with an oxidizing agent such as hexacyanoferrate(III), indicating that they are in mixed forms when expressed in Aspergillus oryzae. His456.458Lys and His456.458Asp mutated as to potential coordinating groups showed weak BO and ferroxidase activities, while His 456.458Va1 mutated as to non-coordinating groups showed no enzyme activity at all.View full abstractDownload PDF (707K) -
Mamoru Matsubara, Nobuhiro Hayashi, Tao Jing, Koiti Titani2003 Volume 133 Issue 6 Pages 773-781
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSEndothelial nitric oxide synthase (eNOS) is a key enzyme in nitric oxide-mediated signal transduction in mammalian cells. Its catalytic activity is regulated both by regulatory proteins, such as calmodulin and caveolin, and by a variety of post-transla-tional modifications including phosphorylation and acylation. We have previously shown that the calmodulin-binding domain peptide is a good substrate for protein kinase C [Matsubara, M., Titani, K., and Taniguchi, H. (1996) Biochemistry 35, 14651-14658]. Here we report that bovine eNOS protein is phosphorylated at Thr497 in the calmodulin-binding domain by PKC both in vitro and in vivo, and that the phosphor-ylation negatively regulates eNOS activity. A specific antibody that recognizes only the phosphorylated form of the enzyme was raised against a synthetic phosphopeptide corresponding to the phosphorylated domain. The antibody recognized eNOS immunoprecipitated with anti-eNOS antibody from the soluble fraction of bovine aortic endothelial cells, and the immunoreactivity increased markedly when the cells were treated with phorbol 12-myristate 13-acetate. PKC phosphorylated eNOS specifically at Thr497 with a concomitant decrease in the NOS activity. Furthermore, the phosphorylated eNOS showed reduced affinity to calmodulin. Therefore, PKC regulates eNOS activity by changing the binding of calmodulin, an eNOS activator, to the enzyme.View full abstractDownload PDF (5621K) -
Seigo Usuki, Yutaka Kariya, Harald Rösner, Masayuki Ishihara2003 Volume 133 Issue 6 Pages 783-790
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSPeriodate-oxidized/borohydride-reduced 2-O-desulfated heparin (OR2DSH) was pre-pared using intact heparin from pig intestine as the starting material. Successive treatments of the heparin by oxidation with sodium periodate and reduction with sodium borohydride yielded periodate-oxidized/borohydride-reduced heparin (OR-heparin). Subsequent 2-O-desulfation of OR-heparin, according to a previously estab-lished method, yielded OR2DSH. Digestion of OR2DSH with heparitinases generated unsaturated disaccharides, comprising 86.5% ΔDiHS-(6, N)S (ΔUA1→4GlcNS(6S)) and 13.5% ΔDiHS-NS (ΔUA1→4GlcNS), as well as undigested oligosaccharides in which uronate moieties were derivatized by the cleavage of the covalent bond between the C-2 and C-3 positions by periodate-oxidation. The molecular mass of OR2DSH was determined to be 11 kDa, which is almost the same as those of other heparin deriva-tives such as 2-O-desulfated heparin (2DSH), 6-O-desulfated heparin (6DSH) and N-desulfated N-reacetylated heparin (NDSNAc-heparin). The ability of OR2DSH to enhance neurite outgrowth-promoting activity was evaluated using the explant cul-ture of neocortical tissue from rat embryo in which endogenous heparan sulfate at the cell surface lost substantial numbers of sulfate groups by the action of 40 μM sodium chlorate. The maximum activity of OR2DSH (29.7%) was achieved at 10 μg/ml, and those of OR-heparin (21.7%), 2DSH (18.7%) and intact heparin (16.3%) were 100 μg/ml, whereas that of NDSNAc-heparin (16.5%) was 1, 000 μg/ml. Completely 6-O-desul-fated heparin (100:6DSH) exhibited very weak activity (3.3%) at 1, 000 μg/ml. These results suggest that the potency of OR2DSH to enhance neurite outgrowth-promoting activity is exerted synergetically by two different components in OR2DSH, i.e., the IdoA αl→4G1cNS(6S) unit, which contains 6-O- and 2-N-sulfate groups, and the uronate moiety in which the covalent bond between C-2 and C-3 is cleaved, although the mode of action remains to be clarified.View full abstractDownload PDF (2223K) -
Tomohiko Kanayama, Satoru Mamiya, Tsutomu Nishihara, Jun-ichi Nishikaw ...2003 Volume 133 Issue 6 Pages 791-797
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSAssessment of the risk of human exposure to man-made chemicals that bind to hormone receptors has emerged as a major public health issue. Among hormone receptors, nuclear receptors tend to be targets of xenobiotics because their endogenous ligands are small, fat-soluble molecules. Nuclear receptors are ligand-inducible transcriptional factors and regulate the transcriptional activity of various target genes. At the start of the initiation step of transcription, nuclear receptors interact with coactivators (TIF2, SRC1, ACTR, CBP/p300, etc.) in an agonist-dependent manner. Using the interaction of the nuclear receptor with a coactivator, we have developed a novel rapid ligand in vitro screening method that is easy to use and has high sensitivity. This method, called by us the CoA-BAP system, is applicable to most nuclear receptors and is suitable for high-throughput screening because the entire experimental operation can be carried out on a microplate. We used human TIF2 as a coactivator including LXXLL motifs expressed in Escherichia coli as a fusion protein with BAP and nuclear receptor LBD expressed in E. coli as a fusion protein with GST. On a GSII-coupled microplate these proteins were incubated with chemicals and the protein-protein interactions were detected as alkaline phosphatase activity. To date we have examined seven nuclear receptors (ERα/β, TRα, RARα/γ, RXRα, and VDR) and confirmed that the method works well.View full abstractDownload PDF (1896K) -
Hitoshi Aoki, Nazmul Ahsan, Shugo Watabe2003 Volume 133 Issue 6 Pages 799-810
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSA cDNA clone encoding a cysteine proteinase of the papain superfamily has been isolated from the hepatopancreas of northern shrimp Pandalus borealis (NsCys). NsCys shares the highest identity of 64% with a cathepsin L-like cysteine proteinase from lobster, and its identity to the well-characterized mammalian cathepsins S, L, and K falls within a narrow range of 54-59%. However, it differs from each of these cathepsins in certain key residues including, for example, the unique occurrence of tryp-tophan and cysteine residues at the structurally important S2 subsite. Consequently, NsCys produced in Pichia pastoris appears to be distinct in various physicokinetic properties. The recombinant enzyme is active and stable over a wide range of pH values, and its substrate specificity is unusual, as demonstrated by its poor affinity for phenylalanine residues. Instead, it shows the highest specificity for proline residues, a property similar to cathepsin K. Unlike cathepsin K, however, NsCys cleaves valine residues more efficiently than leucine. Similar results were obtained with the natural peptide substrate glucagon. The shrimp proteinase is further distinguished by its potent collagenolytic activity, resulting in a cleavage pattern reminiscent of bacterial collagenase. To distinguish such unique structural and enzymatic properties, we propose the trivial name “crustapain” for the shrimp proteinase, indicating that it is a papain-like cysteine proteinase from a crustacean species.View full abstractDownload PDF (4873K) -
Megumi Hirono, Makoto Ojika, Hisatoshi Mimura, Yoichi Nakanishi2003 Volume 133 Issue 6 Pages 811-816
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSH+-pyrophosphatase (H+-PPase), which pumps H+ across membranes coupled with PPi hydrolysis, is found in most plants, and some parasitic protists, eubacteria and archaebacteria. We assayed a number of extracts derived from 145 marine invertebrates as to their inhibitory effect on plant vacuolar H+-PPase. Acylspermidine deriv-atives [RCONH(CH2)3N(CH3)(CH2)4N(CH3)2] from a soft coral (Sinularia sp.) inhibited the PPi-hydrolysis activity of purified H+-PPase and the PPi dependent H+ pump activity (half inhibition concentration, 1μM) of vacuolar membranes of mung bean. The apparent Ki was determined to be 0.9μM. Acylspermidines did not affect the activity of vacuolar H+-ATPase, plasma membrane H+-ATPase, mitochondrial ATPase or cytosolic PPase. Acylspermidines inhibited the acidification of vacuoles in proto-plasts, as found on monitoring by the acridine orange fluorescent method. These results indicate that acylspermidine derivatives represent new inhibitors of H+-PPase with relatively high specificity.View full abstractDownload PDF (2402K) -
Toshiaki Hosaka, Toshiyuki Meguro, Ichiro Yamato, Yasuo Shirakihara2003 Volume 133 Issue 6 Pages 817-823
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSWe report the crystal structure of an enolase from Enterococcus hirae, which is the first report of a structure determination among gram-positive bacteria. We isolated the enolase gene and determined the base sequence The amino acid sequence deduced from the DNA sequence suggests that this enolase is composed of 431 amino acids. The amino acid sequence is very similar to those of enolases from eukaryotic and prokaryotic organisms, being 65% and 50% identical to enolases from Escherichia coli and yeast, respectively. The enolase prepared from E. hirae lysate yielded crystals containing one dimer per asymmetric unit. X-ray diffraction patterns were obtained at 2.8 Å resolution on a SPring-8 synchrotron radiation source. Crystals belong to space group I4 with unit cell dimensions of a=b=153.5 Å, c=90.7 Å. The E. hirae, yeast, E. coli and lobster enolase structures are very similar. The E. hirae enolase takes an “Open” conformation. The regions in the structure that differ most from other enolases are loops L4 (132-140) and L3 (244-265). Considering the positions of these loops relative to the active site, they seem to have no direct involvement in function. Our findings show that the three dimensional structure of an important
enzyme in the glycolytic pathway is evolutionarily conserved among eukaryotes and prokaryotes, including gram-positive bacteria.View full abstractDownload PDF (5245K) -
Masakuni Degawa, Masayuki Namiki, Naoki Yoshimoto, Masanobu Makino, Mi ...2003 Volume 133 Issue 6 Pages 825-831
Published: 2003
Released on J-STAGE: June 30, 2008
JOURNAL FREE ACCESSTwo cultured cell lines, called Kan-R1 and Kan-R2, were established from rat hepatic cells by in vitro culture with a hepatocarcinogen, 3-methoxy-4-aminoazobenzene, and examined for the gene expression of cytochrome P450 (P450) isoforms, CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP3A1 and CYP3A2, by the RT-PCR method. It was revealed that all the P450 genes examined were expressed in both cell lines, although the two cell lines differed in cell size and colony-forming ability on a soft agar. The expression levels of the CYP1A2, CYP2B1, CYP2B2, CYP3A1, and CYP3A2 genes were lower than those in liver tissues, while that of CYP1A1 was higher in the cell lines. In both cell lines, cycloheximide, an inhibitor of protein synthesis, augmented the gene expression of the P450s except CYP2B1. These findings indicate that the newly established hepatic cell lines substantially express the P450 genes for CYP1Al, CYP1A2, CYP2B1, CYP2B2, CYP3A1, and CYP3A2, and that the constitutive gene expression of these P450s, with the exception of CYP2B1, may be inhibited by negative transcription factors.View full abstractDownload PDF (2937K)
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