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Tochigi, Japan

Ushida Y.,Johns Hopkins University | Ushida Y.,Kagome Co. | Talalay P.,Johns Hopkins University
Alcohol and Alcoholism | Year: 2013

Aims: Many East Asians are highly intolerant to even modest alcohol consumption. These individuals accumulate acetaldehyde, the primary metabolite of ethanol, because of a genetic polymorphism of aldehyde dehydrogenase (ALDH) that metabolizes acetaldehyde to nontoxic acetate. The aim of these studies is to upregulate ALDH by dietary means, thereby reducing acetaldehyde toxicity. Methods: Sulforaphane [SF, 1-isothiocyano-4-(methylsulfinyl)butane] derived from its glucosinolate precursor contained in cruciferous vegetables and related inducers of the Keap1/Nrf2/ARE pathway were assessed for their potencies to induce ALDH in murine hepatoma Hepa1c1c7 cells. Inducer potencies for ALDH were compared with those for NQO1, a prototypical cytoprotective enzyme present downstream of the Keap1/Nrf2/ARE pathway. SF (5 or 20 μmol/day) was fed to CD-1 mice for 7 days prior to a single administration of ethanol, and then ALDH induction in organs and pharmacokinetics of acetaldehyde was examined. Results: In addition to SF, other electrophiles, including many Michael reaction acceptors, induce ALDH. Potencies of these agents as inducers parallel their activities in inducing NQO1, and are also dependent on Nrf2. In mice, in vivo, feeding of SF induced tissue ALDH and dramatically increased (doubled) the rate of elimination of acetaldehyde arising from the administration of ethanol. Conclusion: SF and other edible phytochemicals may ameliorate the alcohol intolerance of individuals who are polymorphic with respect to ALDH. © The Author 2013. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Aizawa K.,Kagome Co.
Acta Horticulturae | Year: 2013

Many previous reports have shown that the dietary intake of tomatoes (Lycopersicum esculentum) and tomato products is associated with a reduced risk of chronic diseases. Tomatoes or their components, such as a lycopene, may exert their distinct effects via different mechanisms. However, the biochemical pathways involved in these effects are largely unknown. DNA microarray technology has enabled comprehensive analysis of the expression of a large number of genes simultaneously. Therefore, we used DNA microarrays to investigate the effects of administration of tomato to normal mice on gene expression in the liver. Mice were given tomato beverage (TB) or water (Control) ad libitum for 6 weeks. At 3 weeks, there was no significant difference in body weight between each group, but the body weights and the relative liver weight at 6 weeks in the TB group was significantly lower than those in the Control group. Hepatic gene expression was investigated using DNA microarrays. The ingestion of TB up-regulated the expression of 687 genes and down-regulated the expression of 841 genes, respectively (false discovery rate <0.05). These changes in gene expression suggest that TB ingestion promotes glycogen accumulation and stimulates some specific steps in fatty acid oxidation. In addition, it was indicated the possibility that the decreases in body weight or liver weight loss in the TB group could be attributed to the down-regulation of SREPB-1c and the up-regulation of PPAR α. To our knowledge, the present study is the first to define the effects of tomato on the expression of a large number of genes corresponding to biomarkers in normal mice with microarray technology. The results in this study also demonstrate the importance of consuming tomatoes daily to maintain healthy body conditions and/or reduce the risk of chronic diseases (Aizawa et al., 2009).

Yamaga F.,Hokkaido University | Yamaga F.,Kagome Co. | Washio K.,Hokkaido University | Morikawa M.,Hokkaido University
Environmental Science and Technology | Year: 2010

Phenol-degrading bacteria were isolated from the rhizosphere of duckweed (Lemna aoukikusa) using an enrichment culture method. One of the isolates, P23, exhibited an excellent ability to degrade phenol and attach to a solid surface under laboratory conditions. Phylogenetic analysis revealed that P23 belongs to the genera Acinetobacter and has the highest similarity to Acinetobacter calcoaceticus. P23 rapidly colonized on the surface of sterilized duckweed roots and formed biofilms, indicating that the conditions provided by the root system of duckweed are favorable to P23. A long-term performance test (160 h) showed that continuous removal of phenol can be attributed to the beneficial symbiotic interaction between duckweed and P23. P23 is the first growth-promoting bacterium identified from Lemna aoukikusa. The results in this study suggest the potential usefulness of dominating a particular bacterium in the rhizosphere of duckweeds to achieve efficient and sustainable bioremediation of polluted water. © 2010 American Chemical Society.

Lactic acid bacteria confer a variety of health benefits. Here, we investigate the mechanisms by which Lactobacillus brevis KB290 (KB290) enhances cell-mediated cytotoxic activity. Female BALB/c mice aged 9 weeks were fed a diet containing KB290 (3 × 10(9) colony-forming units/g) or starch for 1 d. The resulting cytotoxic activity of splenocytes against YAC-1 cells was measured using flow cytometry and analysed for gene expression using DNA microarray technology. KB290 enhanced the cell-mediated cytotoxic activity of splenocytes. DNA microarray analysis identified 327 up-regulated and 347 down-regulated genes that characterised the KB290 diet group. The up-regulated genes were significantly enriched in Gene Ontology terms related to immunity, and, especially, a positive regulation of T-cell-mediated cytotoxicity existed among these terms. Almost all the genes included in the term encoded major histocompatibility complex (MHC) class I molecules involved in the presentation of antigen to CD8(+) cytotoxic T cells. Marco and Signr1 specific to marginal zone macrophages (MZM), antigen-presenting cells, were also up-regulated. Flow cytometric analysis confirmed that the proportion of MZM was significantly increased by KB290 ingestion. Additionally, the over-represented Kyoto Encyclopedia of Genes and Genomes pathways among the up-regulated genes were those for natural killer (NK) cell-mediated cytotoxicity and antigen processing and presentation. The results for the selected genes associated with NK cells and CD8(+) cytotoxic T cells were confirmed by quantitative RT-PCR. These results suggest that enhanced cytotoxic activity could be caused by the activation of NK cells and/or of CD8(+) cytotoxic T cells stimulated via MHC class I presentation.

Yokouchi D.,Okayama University | Ono N.,Okayama University | Nakamura K.,Kagome Co. | Maeda M.,Okayama University | Kimura Y.,Okayama University
Glycoconjugate Journal | Year: 2013

In this study, we purified and characterized the β-xylosidase involved in the turnover of plant complex type N-glycans to homogeneity from mature red tomatoes. Purified β-xylosidase (β-Xyl'ase Le-1) gave a single band with molecular masses of 67 kDa on SDS-PAGE under a reducing condition and 60 kDa on gelfiltration, indicating that β-Xyl'ase Le-1 has a monomeric structure in plant cells. The N-terminal amino acid could not be identified owing to a chemical modification. When pyridylaminated (PA-) N-glycans were used as substrates, β-Xyl'ase Le-1 showed optimum activity at about pH 5 at 40 C, suggesting that the enzyme functions in a rather acidic circumstance such as in the vacuole or cell wall. β-Xyl'ase Le-1 hydrolyzed the β1-2 xylosyl residue from Man1Xyl1GlcNAc2-PA, Man1Xyl1Fuc1GlcNAc2-PA, and Man 2Xyl1Fuc1GlcNAc2-PA, but not that from Man3Xyl1GlcNAc2-PA or Man 3Xyl1Fuc1GlcNAc2-PA, indicating that the α1-3 arm mannosyl residue exerts significant steric hindrance for the access of β-Xyl'ase Le-1 to the xylosyl residue, whereas the α1-3 fucosyl residue exerts little effect. These results suggest that the release of the β1-2 xylosyl residue by β-Xyl'ase Le-1 occurs at least after the removal the α-1,3-mannosyl residue in the core trimannosyl unit. © 2012 Springer Science+Business Media, LLC.

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