著者

Tadashi KIHO Shigeyuki USUI Kazuyuki HIRANO Koichi AIZAWA Takahiro INAKUMA

出版者

Japan Society for Bioscience, Biotechnology, and Agrochemistry

雑誌

Bioscience, Biotechnology, and Biochemistry (ISSN:09168451)

巻号頁・発行日

vol.68, no.1, pp.200-205, 2004 (Released:2004-01-24)

参考文献数

31

被引用文献数

67

---

A water-soluble and low-molecular-weight fraction (SB) was obtained from tomato paste. The effects of SB on the formation of advanced glycation end-products (AGE) in protein glycation were studied by the methods of specific fluorescence, ELISA and a Western blot analysis, using the anti-AGE antibody after incubating protein with sugar. The results suggest that SB had strong inhibitory activity, in comparison with aminoguanidine as a positive control, and that the inhibitory mechanism of SB differed from that of aminoguanidine to involve trapping of reactive dicarbonyl intermediates in the early stage of glycation. SB contained an antioxidant, rutin, which showed potent inhibitory activity. The results also suggest that rutin chiefly contributed to inhibiting the formation of AGE, and that other compounds in SB may also have been related to the activity.

著者

横山 雄一 井口 和弘 臼井 茂之 平野 和行 ヨコヤマ ユウイチ イグチ カズヒロ ウスイ シゲユキ ヒラノ カズユキ Yuichi YOKOYAMA Kazuhiro IGUCHI Shigeyuki USUI Kazuyuki HIRANO

雑誌

岐阜薬科大学紀要 = The annual proceedings of Gifu Pharmaceutical University

巻号頁・発行日

vol.62, pp.68-74, 2013-06-30

---

グリセロールは肝臓における糖新生や脂質合成の材料であるため、肝臓へのグリセロール流入量の変化は様々な代謝経路に変調をきたす。アクアポリン9(AQP9)は、主に肝臓において発現が見られ、水分子のみならず、グリセロールや尿素などの低分子溶質をも透過させるチャネル型膜蛋白質である。AMP-activated protein kinase(AMPK)は生体内のエネルギーセンサーであり、糖・脂質代謝の恒常性維持に働くセリン/スレオニンキナーゼである。本研究では、AMPKの活性化剤である、5-aminoimidazole-4-carboxamide-1--D-ribonucleoside(AICAR)を、ヒト肝癌由来HepG2 細胞に作用させたところ、AQP9 mRNA の発現量が顕著に減少することを確認した。レポータージーンアッセイや転写因子forkhead boxa2(Foxa2)遺伝子をノックダウンさせた実験の結果から、Foxa2 は、AICAR によるAQP9 遺伝子発現抑制に関わる重要な転写調節因子であることを見出した。AICAR により活性化されたAMPK は、Akt のThr-308 残基とSer-473 残基のリン酸化を促し、それに伴いFoxa2 がリン酸化されて核内から核外へと移行することを明らかにした。したがって、肝臓でのグリセロール輸送の観点からAMPK によるコントロールのもとに、AQP9 は肝臓へのグリセロールの流入量を変化させ、糖・脂質代謝調節に寄与している可能性が示唆された。

著者

Masato Terashita Kazuhiro Iguchi Shigeyuki Usui Kazuyuki Hirano

出版者

日本医療薬学会

雑誌

医療薬学 (ISSN:1346342X)

巻号頁・発行日

vol.39, no.3, pp.156-165, 2013-03-10 (Released:2014-03-10)

参考文献数

8

---

Anxieties about the quality of generic drugs are one of reasons why these drugs are not generally used in therapies in Japan. To reduce anxieties, we propose a statistical and objective method to evaluate the quality of generic drugs using the coefficient of variances (CVs) calculated from their pharmacokinetic parameters. CVs were estimated from AUC, Cmax, Tmax, t1/2, and MRT, which were provided as publicly-available drug information. The generic drug assessment tool (G-DAT), an original equation derived from the ratio of CVs of corresponding generic to original drugs, and the quality of generic drugs was statistically evaluated. As expected, when evaluated with G-DAT, there was little variance between original and generic drugs using 11 medicines. Antihypertensive dihydropyridines with a lower solubility were shown to have a larger CV. No significant difference in CVs was observed when famotidine and ebastine OD tablets were taken with or without water. G-DAT and the ratio of CVs (CCVs) of generic to original drugs revealed pharmacokinetic equivalences between generic and original drugs. The proposed comparative evaluation showing equivalent pharmacokinetics of generic to original drugs can be used as one solution to reduce anxieties and increase the reliability of generic drugs.