Biomedical subjects

Takashi Tanaka

Publications and source records attributed to Takashi Tanaka.

At least 19 recordsLinked to original sources

PubMed2026

PDLIM4 promotes dephosphorylation of STAT transcription factors by recruiting PTP-BL and inhibits Th1, Th2, and Th17 cell differentiation.

STAT (signal transducers and activators of transcription) transcription factors are activated by tyrosine phosphorylation after cytokine stimulation and are critical for the differentiation of T-helper (Th) cells into particular Th lineage subsets. How STAT-mediated Th cell differentiation is negatively regulated, however, is not fully understood. Here, we report that PDLIM4 binds to STAT3, 4, and 6 and suppresses gene activation mediated by these STATs. PDLIM4 acts as an adaptor that recruits PTP-BL, a protein tyrosine phosphatase, through its LIM (abnormal cell lineage 11-islet 1-mechanosensory abnormal 3) domain, facilitating dephosphorylation of STAT proteins. PDLIM4-deficiency in CD4+ T cells resulted in augmented tyrosine phosphorylation of these STAT proteins and consequently enhanced Th1, Th2, and Th17 cell differentiation, suggesting that PDLIM4 regulates the differentiation of multiple lineages of Th cells by suppressing STAT signaling. We further found that a non-synonymous single-nucleotide polymorphism in PDLIM4, which causes the substitution of a glycine residue with a cysteine in the LIM domain, is associated with susceptibility to rheumatoid arthritis and Graves' disease, both of which are known to be Th17 cell-driven autoimmune diseases. Notably, PDLIM4 containing this amino acid substitution in the LIM domain showed reduced binding to PTP-BL and was therefore partially impaired in its ability to dephosphorylate STAT3 and suppress STAT3 signaling. Our findings define an essential role of PDLIM4 in negatively regulating STAT-mediated Th-cell differentiation and preventing the onset of human autoimmune diseases.

Animals↗

PubMed2007

alpha-Glucosidase inhibitory profile of catechins and theaflavins.

To clarify the postprandial glucose suppression effect of flavonoids, the inhibitory effects of catechins and theaflavins against alpha-glucosidase (AGH) were examined in this study. It was initially demonstrated that theaflavins and catechins preferentially inhibited maltase rather than sucrase in an immobilized AGH inhibitory assay system. For the maltase inhibitory effects of theaflavins, the effects were observed in descending order of potency of theaflavin (TF)-3-O-gallate (Gal) > TF-3,3'-di-O-Gal > TF-3'-O-Gal > TF. This suggests that the AGH inhibition induced by theaflavins is closely associated with the presence of a free hydroxyl group at the 3'-position of TF as well as the esterification of TF with a mono-Gal group. In addition, the R-configuration at the 3'-position of TF-3-O-Gal showed a higher inhibitory activity than the S-configuration. As a result of a single oral administration of maltose (2 g/kg) in rats, a significant reduction in blood glucose level was observed at a dose of 10 mg/kg of TF-3-O-Gal, demonstrating for the first time that TF-3-O-Gal can suppress glucose production from maltose through inhibition of AGH in the gut.

Animals↗

PubMed2007

Identification of alpha-1L and alpha-1A adrenoceptors in human prostate by tissue segment binding.

PURPOSE: Silodosin (KMD-3213 or [(-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2trifluoroethoxy)phenoxy]ethyl}amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide]) (Kissei Pharmaceutical Co., Ltd., Matsumoto, Japan) is a selective antagonist for alpha-1A and alpha-1L adrenoceptors. Using this tritiated ligand the 2 alpha-1 adrenoceptors were examined in binding studies with intact tissue segments and membrane preparations of human prostate, and compared with functionally identified alpha-1 adrenoceptor. MATERIALS AND METHODS: Binding assays with tissue segments and membrane preparations of human prostate samples were performed using [3H]-silodosin and binding affinities for various drugs were estimated. In functional experiments antagonist affinities were evaluated from the inhibitory potency against the contractile response to noradrenaline. RESULTS: [3H]-silodosin bound to intact segments and membrane preparations of human prostate with subnanomolar affinity. [3H]-silodosin binding sites in intact segments were divided into 2 distinct components with different affinities for prazosin and RS-17053 (N-[2(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl1H-indole-3-ethanamine hydrochloride) (Research Biochemicals International, Natick, Massachusetts), while binding in membrane preparations showed single high affinity for these drugs. [3H]-silodosin binding sites also showed high affinity for silodosin and tamsulosin but low sensitivity to BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione) (Research Biochemicals International) in intact segments and in membrane preparations. In functional experiments silodosin and tamsulosin potently inhibited the contractile response to noradrenaline but prazosin, RS-17053 and BMY 7378 showed low antagonistic affinity. CONCLUSIONS: The current binding studies in human prostate samples clearly show that alpha-1L and alpha-1A adrenoceptors coexist as pharmacologically distinct entities in intact tissues but not in crude membrane preparations. Also, alpha-1 adrenoceptors involved in the contractile response to noradrenaline are the alpha-1L subtype.

Humans↗

PubMed2006

[Evaluation of irradiation position in respiratory-gated radiotherapy using a phantom system simulating patient respiration].

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. The present study was conducted to evaluate the treatment field in RG radiotherapy using a phantom system simulating patient respiration. A phantom system consisting of a 3-cm ball-shaped dummy tumor and film placed in a cork lung phantom was used (THK Co., Ltd.). RG radiotherapy was employed in the expiratory phase. The phantom movement distance was set to 2 cm, and the gating signals from a respiratory-gating system (AZ-733V, Anzai Medical) were varied. The settings used for irradiation were an X-ray energy of 6 MV (PRIMUS, Toshiba Medical Systems), treatment field of 5 cm x 7 cm, and X-ray dose of 100 MU. Images were acquired using an electric portal-imaging device (EPID, OPTIVUE 500), and the X-ray dose distribution was measured by the film method. In images acquired using the EPID, the tumor margins became less clear when the gating signals were increased, and the ITVs were determined to be 3.6 cm, 3.7 cm, 4.2 cm, and 5.1 cm at gating rates of 10%, 25%, 50%, and no gate, respectively. With regard to the X-ray dose distribution measured by the film method, the dose profile in the cephalocaudal direction was shifted toward the expiratory phase, and the degree of shift became greater when the gating signals were increased. In addition, the optimal treatment fields in the cephalocaudal direction were determined to be 5.2 cm, 5.2 cm, 5.6 cm, and 7.0 cm at gating rates of 10%, 25%, 50%, and no gating, respectively. Although RG radiotherapy is useful for improving the accuracy of radiotherapy, the characteristics of the RG radiotherapy technique and the radiotherapy system must be clearly understood when this method is to be employed in clinical practice. Image-guided radiotherapy (IGRT) is now assuming a central role in radiotherapy, and properly identifying internal margins is an important issue for ensuring optimal treatment. The results of this study confirmed that it is necessary to ensure the optimal treatment field in radiotherapy of the trunk and that it is essential to confirm tumor position on the basis of image evaluation.

Humans↗

PubMed2006

Tudor-related proteins TDRD1/MTR-1, TDRD6 and TDRD7/TRAP: domain composition, intracellular localization, and function in male germ cells in mice.

The germ-line cells of many animals possess a characteristic cytoplasmic structure termed nuage or germinal granules. In mice, nuage that is prominent in postnatal male germ cells is also called intermitochondrial cement or chromatoid bodies. TDRD1/MTR-1, which contains Tudor domain repeats, is a specific component of the mouse nuage, analogously to Drosophila Tudor, a constituent of polar granules/nuage in oocytes and embryos. We show that TDRD6 and TDRD7/TRAP, which also contain multiple Tudor domains, specifically localize to nuage and form a ribonucleoprotein complex together with TDRD1/MTR-1. The characteristic co-localization of TDRD1, 6 and 7 was disrupted in a mutant of mouse vasa homologue/DEAD box polypeptide 4 (Mvh/Ddx4), which encodes another evolutionarily conserved component of nuage. In vivo over-expression experiments of the TDRD proteins and truncated forms during male germ cell differentiation showed that a single Tudor domain is a structural unit that localizes or accumulates to nuage, but the expression of the truncated, putative dominant negative forms is detrimental to meiotic spermatocytes. These results indicate that the Tudor-related proteins, which contain multiple repeats of the Tudor domain, constitute an evolutionarily conserved class of nuage components in the germ-line, and their localization or accumulation to nuage is likely conferred by a Tudor domain structure and downstream of Mvh, while the characteristic repeated architecture of the domain is functionally essential for the differentiation of germ cells.

Amino Acid Sequence↗

PubMed2006

[Examination of PET image evaluation experimentation method aiming at improved accuracy of data acquisition].

Multiple data evaluation is desirable for data obtained by positron emission tomography (PET), as the data follow the Poisson distribution. Such evaluation, however, tends to be very complicated, since the count- rates change with nuclide decay. To solve this problem, we propose a new data scan protocol in this communication. With this method, the true+scatter coincidence counts were computed during the initial one-minute scanning, which was fixed as the standard. A dynamic scan was then performed with the fixed counts from the high count-rate region. Regions with +/-2.5% of the image noise of the standard image was chosen to provide the data for evaluation. These were found to be the regions of 16.5-25.5 kcps (2D) and 81.1-138.5 kcps. Image quality was found to be affected by noise (2D) and random coincidence. Using this method, multiple data could be obtained by a single experiment, and very reliable image evaluation could be done.

Positron-Emission Tomography↗

PubMed2006

The effect of gradually graded shear stress on the morphological integrity of a huvec-seeded compliant small-diameter vascular graft.

The premature endothelialization of tissue-engineered grafts had often induced cellular detachment at an early period of implantation in arterial circulation, resulting in occlusion at an early period of implantation. This study was aimed to determine whether gradually increased shear stress applied ex vivo improves cell retention and tissue morphological integrity including cell shape and alignment, actin fiber alignment and expression of vascular endothelial (VE) cadherin. Tissue-engineered grafts used for this study were human umbilical vein endothelial cell (HUVEC)-seeded compliant small-diameter grafts made of poly(L-lactide-co-epsilon-caprolactone) fiber meshes fabricated by electrospinning. The shear stresses applied to grafts, generated using a custom-designed mock circulatory apparatus, were 3.2, 8.7 and 19.6 dyn/cm(2). The grafts completely monolayered prior to shear stress exposure exhibited a polygonal cobblestone morphology with randomly distributed actin fibers and VE cadherin at the continuous peripheral region of adjacent cells. The 24-h-loading of high shear stresses (8.7 and 19.6 dyn/cm(2)) equivalent to those of the arterial circulatory system resulted in severe cellular damage resulting in the complete loss of cells. However, a gradually increased graded exposure from a low (3.2 dyn/cm(2)) to a high shear stress (19.6 dyn/cm(2)) resulted in a markedly reduced cell detachment, a highly elongated cell shape, and orientation or alignment of both cells and actin fibers, which were parallel to the direction of flow. Although VE-cadherin expression was not detected yet, a higher degree of tissue integrity was achieved, which may greatly improve the performance particularly at an early period of implantation.

Arteries↗

PubMed2006

Coffee consumption and reduced risk of hepatocellular carcinoma among patients with chronic type C liver disease: A case-control study.

Several studies have reported the role of coffee for hepatocellular carcinoma (HCC). However, no study investigated about the relation of coffee for HCC among individuals with a relevant risk factor, i.e., hepatitis C virus (HCV) infection. Thus, we conducted a hospital-based case-control study to assess an association between coffee and HCC, in which both 73 cases and 253 controls were patients with chronic type C liver disease. To consider potential changes in coffee intake due to progression of liver disease, the effect of coffee was estimated separately before and after first identification of liver disease. Odds ratios (OR) and 95% confidence intervals (CI) for HCC risk were calculated using the conditional logistic regression model. Coffee drinking on a daily basis (>/=1cup/day) revealed lowered ORs as compared with non-drinkers both before first identification of liver disease (OR 0.38; 95% CI: 0.13-1.12; P=0.078) as well as thereafter (OR 0.19; 95% CI: 0.05-0.71; P=0.032). Even after excluding subjects who reported a reduction in the frequency of coffee intake after first identification of liver disease, this negative correlation persisted (OR 0.35; 95% CI: 0.12-1.06; P=0.063). Taken together, coffee may be a protective factor for HCC among those infected with HCV.

Journal Article↗

PubMed2006

[Evaluation of absorbed dose in respiratory-gated radiotherapy using a phantom system that simulates patient respiration].

Respiratory-gated (RG) radiotherapy is useful for minimizing the irradiated volume of normal tissues resulting from the shifting of internal structures caused by respiratory movement. In this technique, although improvement in the dose distribution of the target can be expected, the actual absorbed dose distribution is not clearly determined. Therefore, it is important to clarify the absorbed dose at the tumor and at the evaluation points according to the patient's respiration. We have developed a phantom system that simulates patient respiration (TNK Co., Ltd.), to evaluate the absorbed dose and ensure precise RG radiotherapy. Actual patient respiratory signals were obtained using a respiratory synchronization and gating system (AZ-733V, Anzai Medical). The acquired data were then transferred to a phantom system driven by a ball screw to simulate the shifting of internal structures caused by respiratory movement. We measured the absorbed dose using a micro-ionization chamber dosimeter and the dose distribution using the film method for RG irradiation at expiratory phase by using Linac (PRIMUS, Toshiba Medical Systems Corp.) X-rays. When the distance of phantom movement was set to the average patient respiratory movement distance of 1.5 cm, we first compared absorbed dose with RG irradiation with a gating signal of 50% or less, and without RG irradiation. The absorbed dose at the iso-center was improved by 6.0% and 4.4% at a field size of 4x4 cm2, and by 1.3% and 0.7% at a field size of 5x5 cm2 with an X-ray energy of 6 MV and 10 MV, respectively. There was, however, no dose change at a field size of 10x10 cm2 and 15x15 cm2. When the gating signal was reduced to 25% and 10%, absorbed dose was also improved. With regard to the flatness of the dose profile, no changes in dose distribution were observed in the lateral direction, e.g., beam flatness was within 1.4% and 1.6% at field sizes of 5x5 cm2 and 10x10 cm2, respectively, with an X-ray energy of 6 MV. In the cranial-caudal direction, the dose profile was relatively large even if a gating signal of 50% was applied, i.e., 8.1% and 10.4% at field sizes of 5x5 cm2 and 10x10 cm2, respectively. Beam flatness without RG was much worse, i.e., 37.8% and 38.2%, at field sizes of 5x5 cm2 and 10x10 cm2, respectively. In both cases, the dose was insufficient in the expiratory direction. Although RG radiotherapy is quite useful, the margins in the inspiratory and expiratory phases should be considered based on the level of gating signal and field size in order to formulate appropriate radiotherapy planning in terms of the shifting of internal structures. To ensure accurate radiotherapy, the characteristics of the RG irradiation technique and the radiotherapy equipment must be clearly understood when this technique is to be employed in clinical practice.

Humans↗

PubMed2006

Pharmacological evaluation of plasma membrane beta-adrenoceptors in rat hearts using the tissue segment binding method.

This study evaluates beta-adrenoceptors in rat atria and ventricle using the tissue segment binding method and compares the results with those obtained using conventional homogenate binding assays. In studies with tissue segment binding, the hydrophilic radioligand [(3)H]-CGP12177 selectively bound to plasma membrane beta-adrenoceptors, and the B(max) levels were significantly higher than those obtained with homogenate binding. However, both binding approaches revealed similar proportions of beta(1)- and beta(2)-adrenoceptors. The regional distribution of plasma membrane beta(1)- and beta(2)-adrenoceptors in rat hearts were also determined using tissue segment binding. Abundance of beta-adrenoceptors and proportion of beta(1)-adrenoceptors were higher in atria than in ventricle, but there was no significant difference between right and left atria or within ventricle (right and left ventricle free walls, apex, and interventricular septum). To establish the ability of the tissue segment binding method to study beta-adrenoceptor regulation such as the internalization of receptors, the effect of prolonged exposure of rat ventricle to (-)-isoprenaline was also investigated by using tissue segments and homogenate binding. Incubation with (-)-isoprenaline for 1 h in vitro caused a concentration-dependent decrease in the density of beta-adrenoceptors, predominantly beta(2)-adrenoceptors, when assessed with tissue segment binding method. In contrast, the subtype-specific change after treatment with (-)-isoprenaline was not detected using homogenate binding. In summary, the tissue segment binding method with [(3)H]-CGP12177 enables a more precise quantitation of plasma membrane beta(1)- and beta(2)-adrenoceptors in rat hearts and is suitable for studying their regulation.

Adrenergic beta-Agonists↗

PubMed2006

IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9.

The Toll-like receptor (TLR) family has important roles in microbial recognition and dendritic cell activation. TLRs 7 and 9 can recognize nucleic acids and trigger signalling cascades that activate plasmacytoid dendritic cells to produce interferon-alpha (IFN-alpha) (refs 7, 8). TLR7/9-mediated dendritic cell activation is critical for antiviral immunity but also contributes to the pathogenesis of systemic lupus erythematosus, a disease in which serum IFN-alpha levels are elevated owing to plasmacytoid dendritic cell activation. TLR7/9-induced IFN-alpha induction depends on a molecular complex that contains a TLR adaptor, MyD88, and IFN regulatory factor 7 (IRF-7) (refs 10-14), but the underlying molecular mechanisms are as yet unknown. Here we show that IkappaB kinase-alpha (IKK-alpha) is critically involved in TLR7/9-induced IFN-alpha production. TLR7/9-induced IFN-alpha production was severely impaired in IKK-alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine induction was decreased but still occurred. Kinase-deficient IKK-alpha inhibited the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7. Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a potential target for manipulating TLR-induced IFN-alpha production.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Relationship between acetabular labrum evaluation by using radial magnetic resonance imaging and progressive joint space narrowing in mild hip dysplasia.

OBJECTIVE: The aim of this study was to investigate the relationship between abnormal acetabular labrum depicted by radial magnetic resonance and progressive joint space narrowing (JSN) of hip dysplasia. METHODS: Subjects were 23 joints [21 patients; mean age: 35.1 years (16-53 years)] that had acetabular dysplasia with lateral center-edge angle of Wiberg (CE angle) greater than 5 degrees and smaller than 25 degrees (mean, 16.4 degrees ), which did not show any arthrotic changes on plain radiograms and were followed up for 3 years or longer. Radial images of acetabular labrum were classified into three stages. RESULTS: Progression of JSN was not significantly related to CE angle but to progression of MRI stage (P=.006). In multivariate analysis, one rank progression of MRI stage was significantly associated with progression of JSN (adjusted OR=11.41, 95% CI: 1.51-86.24, P=.018). CONCLUSION: Our findings showed that in patients whose acetabular dysplasia has 5-25 degrees CE angle, MRI staging based on radial MRI is a better factor for prediction of progression of JSN than CE angle.

Acetabulum↗

PubMed2006

Does alcohol increase the risk of hepatocellular carcinoma among patients with hepatitis C virus infection?

We conducted a hospital-based case-control study to investigate the effects of alcohol drinking on hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV) infection, with special reference to the disease course and changes in drinking habits. From among 1159 HCV-RNA positive patients under clinical follow-up at Osaka City University Hospital (OCUH), we identified 73 cases newly diagnosed with HCC during the past 3 years and selected 253 matched controls without HCC. The odds ratios were calculated for cumulative and average daily ethanol consumption, during three different periods (lifetime, before, and after the first identification of liver disease), using a logistic regression model. Among all subjects, there was a trend towards an inverse association between HCC and lifetime ethanol consumption (P=0.059-0.066). The tendency was similar for ethanol consumption before the first identification of liver disease, while no associative trend was indicated after the first identification. Among those with minor changes on abdominal ultrasonography findings at the first OCUH visit, a positive association was suggested for ethanol intake after the first identification, although results were not statistically significant. In conclusion, our results did not demonstrate a strong positive association between alcohol drinking and HCV-related HCC in this population.

Journal Article↗

PubMed2006

Antibacterial spectrum of plant polyphenols and extracts depending upon hydroxyphenyl structure.

The relationship between the structure and antibacterial activity of 22 polyphenols was analyzed by using minimum inhibitory concentration (MIC) as a criterion against 26 species of bacteria which can grow in Mueller-Hinton medium. There was no clear correlation between Gram-staining and bacterial susceptibility to polyphenols, and the extent of the susceptibility was approximately dependent on the species of bacteria. In the same Gram-negative bacteria, the antibacterial activity of the polyphenols against Aeromonas hydrophila, Vibrio parahaemolyticus and Vibrio vulnificus was comparatively strong. On the other hand, the activity against 11 species of the Enterobacteriaceae was comparatively weak, and the activity against six species of aerobic bacteria causing plant disease was moderate. Polyphenols having pyrogallol groups showed strong antibacterial activity, and those with catechol and resorcinol rings showed lower activity. The structure-activity relationship was extended to 26 polyphenol-rich plant extracts which could have potent antibacterial activity suitable for commercial use.

Anti-Bacterial Agents↗

PubMed2006

[Alpha1-adrenoceptor subtypes and alpha1-adrenoceptor antagonists].

Alpha(1)-adrenoceptors are widely distributed in the human body and play important physiologic roles. Three alpha(1)-adrenoceptor subtypes (alpha(1A), alpha(1B) and alpha(1D)) have been cloned and show different pharmacologic profiles. In addition, a putative alpha(1)-adrenoceptor (alpha(1L) subtype) has also been proposed. Recently, three drugs (tamsulosin, naftopidil, and silodosin) have been developed in Japan for the treatment of urinary obstruction in patients with benign prostatic hyperplasia. In this review, we describe recent alpha(1)-adrenoceptor subclassifications and the pharmacologic characteristics (subtype selectivity and clinical relevance) of alpha(1)-adrenoceptor antagonists.

Adrenergic alpha-1 Receptor Antagonists↗

PubMed2006

Factors associated with functional limitation in stair climbing in female Japanese patients with knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) of the knee is a common form of arthritis, and affects quality of life. We investigated factors associated with functional limitation in stair climbing among female Japanese patients with knee OA. As weight is a known risk factor for knee OA, we focused on body weight at 40 years of age, and examined the association with present weight, past weight, and weight change. METHODS: Subjects were 360 Japanese women aged 40-92 years who were newly diagnosed with knee OA at 3 university hospitals over a 1-year period. Factors associated with the severity of functional limitation in stair climbing were assessed by calculating odds ratios (OR) using the proportional odds model in logistic regression. RESULTS: Weight at diagnosis showed a positive association with severe functional limitation in stair climbing; however, a negative association was observed for weight change since age 40. Further analysis indicated that the association with weight at age 40 (highest vs. lowest quartile, OR=2.84, 95% confidence interval: 1.03-7.83, trend p=0.071) is stronger than weight at diagnosis. Other significant characteristics were age (70+ vs. 40-59 years, OR=7.37), previous knee pain and/or swelling 12 years or more before diagnosis (OR=2.67), and physical work (OR=1.94). In addition, higher parity was found to be a negatively associated factor (for tripara or more, OR=0.41). CONCLUSIONS: This study identified factors, such as heavy weight at age 40 and physical labor, which are potentially useful for preventing severe functional limitation for female knee OA patients. In addition, higher parity was associated with milder stair climbing limitation.

Adult↗

PubMed2005

Hex stimulates the hepatocyte nuclear factor 1alpha-mediated activation of transcription.

The homeodomain protein Hex can function either as a transcriptional repressor or activator in animals. Recent reports have indicated that Hex is involved in liver development. However, its target genes and interacting proteins are largely unknown. We found that Hex functionally interacted with hepatocyte nuclear factor (HNF) 1alpha to further stimulate its activity using reporter gene containing multiple copies of HNF1alpha-binding site of the L-type pyruvate kinase (L-PK) gene promoter or natural L-PK promoter. This stimulation required the homeodomain and the acidic carboxyl-terminal region of Hex. Over-expression of Hex in primary cultured hepatocytes resulted in stimulation of the L-PK gene expression. Glutathione S-transferase pull-down assay and co-immunoprecipitation revealed that Hex physically interacted with HNF1alpha in mammalian cells through the homeodomain of Hex and POU-homeodomain of HNF1alpha. Since HNF1alpha is an important liver-enriched transcription factor involved in liver differentiation, Hex may contribute to liver differentiation through interaction with HNF1alpha.

Base Sequence↗

PubMed2005

A novel black tea pigment and two new oxidation products of epigallocatechin-3-O-gallate.

During tea fermentation, oxidation-reduction dismutation of a number of quinone metabolites of tea catechins yields numerous minor products, which make it difficult to separate and purify black tea polyphenols. In this study, epigallocatechin-3-O-gallate was enzymatically oxidized and then the unstable quinone metabolites in the oxidation mixture were hydrogenated with 2-mercaptoethanol to reduce production of inseparable minor dismutation products. As a result, three new oxidation products including a new black tea pigment were isolated, and their structures were determined based on chemical and spectroscopic data. Dehydrotheasinensin AQ is a new reddish-orange pigment with a 1,2-diketone structure, and its presence in commercial black tea was confirmed. In addition, a new quinone dimer with a complex caged structure and a trimer of epigallocatechin-3-O-gallate were also isolated and their production mechanisms are proposed. The presence of this trimer suggested participation of galloyl quinones in production of minor polyphenols in black tea.

Catechin↗