 |
 |
|
教 授 |
永田 清 |
|
講 師 |
坂口修平 熊谷 健 |
|
助 教 |
佐々木崇光 |
|
|
D 3 |
髙橋昌悟 |
|
|
D 1 |
稲見敬太 佐藤 裕 |
|
|
M 2 |
沼田喜弘 |
|
|
M 1 |
清松孝行 佐々木瞳 中澤洋一 野崎智紀 |
|
|
薬学6年 |
小西麻美子 榊 聡美 角間元美 齋藤詩奈子 千葉文博 笠原
彩 伏見 彩 阿部大紀 菅野高弘 齋藤雄大
|
|
|
薬学5年 |
齋藤由貴 木村薫子 工藤裕太 石橋幸奈 竹屋里恵 近江知世 根本あゆみ 船越広大 山内菜弥 渡辺美智子 草刈慎太郎 小林英嗣 横川優里
|
|
|
生命4年 |
髙橋里菜 吉田美都里
|
|
|
|
|
|
 |
当教室では薬学領域における医薬品安全性学および環境衛生学の観点から、薬物代謝を中心とした以下のテーマについて研究を進めている。
1．薬物や環境汚染物質などの毒性発現における個人差の分子メカニズム解明に関する研究
薬物や環境汚染物質などを摂取することによって引き起こされる毒性発現の程度は、個人間で大きく異なっている。その原因として、遺伝的な要因と環境的な要因が主に考えられる。本研究においては、遺伝的な要因についての原因解明のために遺伝子単離解析、人工的に発現させたタンパク質の機能解析およびヒトタンパク質を遺伝子操作により置き換えたヒト型実験動物を用いた研究を行っている。
２．薬物や環境汚染物質のバイオアッセイに関する研究（ハイスループット測定法の構築）
化学物質の毒性発現評価法には、種々の培養細胞を用いたバイオアッセイ系が主に使用されている。本研究においては、医薬品、農薬および環境ホルモン等の環境中に放出された人工化学物質が生態系にどのような影響を及ぼすのかを明らかにするために毒性発現評価を簡便でより正確に、しかも迅速に測定可能な培養細胞の人工的な構築を行っている。
３．医薬品の代謝および副作用発現予測評価系の構築に関する研究
医薬品の副作用の発現を予測することは重要であるが、薬物の代謝活性化が関わる副作用の発現予測は難しい。その原因の一つに薬物代謝活性には大きな種差、個人差の存在が挙げられる。そこで本研究室ではヒト人工多能性幹細胞（iPS細胞）ライブラリーを樹立し、それを医薬品の前臨床薬物動態試験に現在用いられているヒト初代培養細胞と同等の機能を持った肝細胞に効率よく分化させ、医薬品の代謝および副作用発現予測が可能となる評価系の確立を目指している。
|
 |
2012年
Hepatocyte nuclear factor 6 enhances the expression of the CYP3A4 gene in hepatocyte-like cells differentiated from human induced pluripotent stem cellsa
Takamitsu Sasaki, Shogo Takahashi, Yoshihiro Numata Masayo Narita, Yutaka Tanaka, Yuki Kondo, Takeshi Kumagai, Tamihide Matsunaga, Shigeru Ohmori, Kiyoshi Nagata
Drug Metab. Pharmacokinet., in press (2012)
敗血症モデルとしてのTNF-alpha誘導肝細胞死と酸化ストレス シグナル伝達機構からのアプローチ
坂口修平、高橋昌吾、熊谷 健、佐々木崇光、永田 清
エンドトキシン･自然免疫研究15 エンドトキシン･自然免疫研究会編, 53-57 (2012)
Mechanisms of CYP3A Induction by Glucocorticoids in Human Fetal Liver Cells
Tamihide Matsunaga, Masataka Maruyama, Tsutomu Matsubara, Kiyoshi Nagata, Yasushi Yamazoe, Shigeru Ohmori
Drug Metab. Pharmacokinet., 27, 653-657 (2012)
Effects of Hypoxia-Inducible Factor-1alpha Chemical Stabilizer, CoCl(2) and Hypoxia on Gene Expression of CYP3As in Human Fetal Liver Cells
Eiji Suzuki, Tamihide Matsunaga, Akiko Aonuma, Takamitsu Sasaki, Kiyoshi Nagata, Shigeru Ohmori
Drug Metab. Pharmacokinet., 27, 398-404 (2012)
Polycyclic aromatic hydrocarbons activate CYP3A4 gene transcription through human pregnane X receptor
Takeshi Kumagai, Hiroyuki Suzuki, Takamitsu Sasaki, Shuhei Sakaguchi, Shinichi Miyairi, Yasushi Yamazoe, Kiyoshi Nagata
Drug Metab. Pharmacokinet., 27, 200-206 (2012)
|
2011年
Tumor Necrosis Factor-Alpha-Nuclear Factor-Kappa B-Signaling Enhances St2b2 Expression during 12-O-Tetradecanoylphorbol-13-acetate-Induced Epidermal Hyperplasia
Toshihiro Matsuda, Miki Shimada, Akira Sato, Takanori Akase, Kouichi Yoshinari, Kiyoshi Nagata, Yasushi Yamazoe
Biol. Pharm. Bull., 34, 183-190 (2011)
Progression of Alcoholic and Non-alcoholic steatohepatitis: Common Metabolic Aspects of Innate Immune System and Oxidative Stress
Shuhei Sakaguchi, Shogo Takahashi, Takamitsu Sasaki, Takeshi Kumagai, Kiyoshi Nagata
Drug Metab. Pharmacokinet., 26, 30-46 (2011)
|
2010年
Malondialdehyde-modified low density lipoprotein (MDA-LDL)-induced cell growth was suppressed by polycyclic aromatic hydrocarbons (PAHs)
Hiroyuki Suzuki, Takamitsu Sasaki, Takeshi Kumagai, Shuhei Sakaguchi, Kiyoshi Nagata
J. Toxicol. Sci., 35, 137-147 (2010)
Construction of a System that Simultaneously Evaluates CYP1A1 and CYP1A2 Induction in a Stable Human-derived Cell Line using a Dual Reporter Plasmid
Wataru Sato, Hiroyuki Suzuki, Takamitsu Sasaki, Takeshi Kumagai, Shuhei Sakaguchi, Michinao Mizugaki, Shinichi Miyari, Yasushi Yamazoe, Kiyoshi Nagata
Drug Metab. Pharmacokinet., 25, 180-189 (2010)
Kinetics of 6-thioxanthine metabolism by allelic variants of xanthine oxidase
Mutsumi Kudo, Takamitsu Sasaki, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka
Drug Metab. Pharmacokinet., 25, 361-366 (2010)
Functional characterization of 26 CYP2B6 allelic variants (CYP2B6. 2-CYP2B6. 28 expect CYP2B6. 22)
Takashi Watanabe, Kaneko Sakuyama, Takamitsu Sasaki, Yuya Ishii, Masaaki Ishikawa, Noriyasu Hirasawa, Masahiro Hiratsuka
Pharmacogenet. Genomics., 20, 459-462 (2010)
|
2009年
Involvement of Vitamin D receptor in the intestinal induction of human ABCB1
Shuko Tachibana, Kouichi Yoshinari, Tsubasa Chikada, Takayoshi Toriyabe, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Dispos., 7, 1604-1610 (2009)
Simultaneous expression of plural forms of human cytochrome P450 at desired ratios in HepG2 cells: adenovirus-mediated tool for cytochrome P450 reconstitution
Kazunobu Aoyama, Kouichi Yoshinari, Hye-ji Kim, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Pharmacokinet., 24, 209-217 (2009)
Unveiling a new essential cis-element for the transactivation of the CYP3A4 gene by xenobiotics
Takayoshi Toriyabe, Kiyoshi Nagata,1 Tomonari Takada, Yusuke Aratsu, Tsutomu Matsubara, Kouichi Yoshinari, Yasushi Yamazoe
Mol. Pharmacol., 75, 677-684 (2009)
Interaction of cytochrome P450 3A4 and UDP-glucuronosyltransferase 2B7: evidence for oprotein-protein association and possible involvement of CYP3A4 J-helix in the interaction
Shuso Takeda, Yuji Ishii, Megumi Iwanaga, Arief Nurrochmad, Yuji Ito, Peter I. Mackenzie, Kiyoshi Nagata, Yasushi Yamazoe, Kazuta Oguri, Hideyuki Yamada
Mol. Pharmacol., 75, 956-964 (2009)
Drug Metabolism Catalyzed by Cytochrome P450
Kiyoshi Nagata
Folia Pharmacol. Jpn., 134, 146-148 (2009)
|
2008年
Expression of a skin cholesterol sulfotransferase, St2b2, is a trigger of epidermal cell differentiation
Miki Shimada, Toshihiro Matsuda, Akira Sato, Takamori Akase, Tsutomu Matsubara, Kiyoshi Nagata, Yasushi Yamazoe
Xenobiotica, 38, 1487-1499 (2008)
Role of vitamin D receptor in the lithocholic acid-mediated CYP3A induction in vitro and in vivo
Tsutomu Matsubara, Kouichi Yoshinari, Kazunobu Aoyama, Mika Sugawara, Yuji Sekiya, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Dispos., 36, 2058-2063 (2008)
Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements
Kouichi Yoshinaria, Rika Ueda, Kazutomi Kusano, Tsutomu Yoshimura, Kiyoshi Nagata, Yasushi Yamazoe
Biochem. Pharmacol., 76, 139-145 (2008)
|
2007年
Assessment of Human Pregnane X Receptor Involvement in Pesticide-Mediated Activation of CYP3A4 Gene
Tsutomu Matsubara, Wachiraporn Noracharttiyapot, Takayoshi Toriyabe, Kouichi Yoshinari, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Dispos.. 35, 728-733 (2007)
Genetic Polymorphism of Aldehyde Oxidase in Donryu Rats
Kunio Itoh, Akiko Masubuchi, Takamitsu Sasaki, Mayuko Adachi, Nobuaki Watanabe, Kiyoshi Nagata, Yasushi Yamazoeb, Masahiro Hiratsuka, Michinao Mizugaki, Yorihisa Tanaka
Drug Metab, Dispos., 35, 734-739 (2007)
Broad but Distinct Role of Pregnane X Receptor on the Expression of Individual Cytochrome P450s in Human Hepatocytes
Koki Kojima, Kiyoshi Nagata, Tsutomu Matsubara, Yasushi Yamazoe
Drug Metab. Pharmacokinet., 22, 276-286 (2007)
Role of Human Hepatocyte Nuclear Factor 4α in the Expression of Drug-Metabolizing Enzymes and Transporters in Human Hepatocytes Assessed by Use of Small Interfering RNA
Yoshiteru Kamiyama, Tsutomu Matsubara, Kouichi Yoshinari, Kiyoshi Nagata, Hidetaka Kamimura, Yasushi Yamazoe
Drug Metab. Pharmacokinet., 22, 287-298 (2007)
Effect of Pregnane X Receptor Ligand on Pharmacokinetics of Substrates of Organic Cation Transporter Oct1 in Rats
Tomoji Maeda, Masanobu Oyabu, Takafumi Yotsumoto, Ryunosuke Higashi, Kiyoshi Nagata, Yasushi Yamazo, Ikumi Tamai
Drug Metab. Dispos., 35, 1580-1586 (2007)
Protein-Protein Interactions between Rat Hepatic Cytochromes P450 (P450s) and UDP-Glucuronosyltransferases (UGTs): Evidence for the Functionally Active UGT in P450-UGT Complex
Yuji Ishii, Megumi Iwanaga, Yoshio Nishimura, Shuso Takeda, Shin-ichi Ikushiro, Kiyoshi Nagata, Yasushi Yamazoe, Peter I. Mackenzie, Hideyuki Yamada
Drug Metab. Pharmacokinet., 22, 367-376 (2007)
Common Pathogenic Mechanism in Development Progression of Liver Injury Caused by Non-Alcoholic or Alcoholic Steatohepatitis
Kiyoshi Nagata, Hiroyuki Suzuki, Shuhei Sakaguchi
J. Toxicol. Sci., 32, 453-468, (2007)
|
2006年
Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase
Masaaki Miyata, Yoshiki Matsuda, Hiroyuki Tsuchiya, Hirotaka Kitada, Takanori Akase, Miki Shimada, Kiyoshi Nagata, Frank J. Gonzalez, Yasushi Yamazoe
Drug Metab. Pharmacokinet., 21, 315-323 (2006)
Role for enhanced faecal excretion of bile acid in hydroxysteroid sulfotransferase-mediated protection against lithocholic acid-induced liver toxicity
Masaaki Miyata, Hirotaka Watase, Wataru Hori, Miki Shimada, Kiyoshi Nagata, Frank J. Gonzalez, Yasushi Yamazoe
Xenobiotica, 36, 631-644 (2006)
Induction of human CYP2A6 is mediated by the pregnane X receptor with peroxisome proliferator-activated receptor-{gamma} coactivator 1{alpha}
Masahiro Itoh, Miki Nakajima, Eriko Higashi, Ryoko Yoshida, Kiyoshi Nagata, Yasushi Yamazoe, Tsuyoshi Yokoi
J. Pharmacol. Exp. Ther., 319, 693-702 (2006)
Construction of several human-derived stable cell lines displaying distinct profiles of CYP3A4 induction
Wachiraporn Noracharttiyapot, Yoko Nagai, Tsutomu Matsubara, Masaaki Miyata, Miki Shimada, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Pharmacokinet., 21, 99-108 (2006)
Detection of a new N-oxidized metabolite of flutamide, N-[4-nitro-3-(trifluoromethyl)phenyl]hydroxylamine, in human liver microsomes and urine of prostate cancer patients
Rika Goda, Daichi Nagai, Yuji Akiyama, Kiyohiro Nishikawa, Isao Ikemoto, Yoshio Aizawa, Kiyoshi Nagata, Yasushi Yamazoe
Drug Metab. Dispos., 34, 828-835 (2006)
A common regulatory region functions bidirectionally in transcriptional activation of the human CYP1A1 and CYP1A2 genes
Rika Ueda, Hiromi Iketaki, Kiyoshi Nagata, Shioko Kimura, Frank J. Gonzalez, Kazutomi Kusano, Tsutomu Yoshimura, Yasushi Yamazoe
Mol. Pharmacol., 69, 1924-1930 (2006)
Prediction of drug-drug interactions for AUCoral of high clearance drug from in vitro data: utilization of a microtiter plate assay and a dispersion model
Takahito Yamamoto, Akio Suzuki, Yoshiro Kohno, Kiyoshi Nagata, Yasushi Yamazoe
Curr. Drug Metab., 7, 135-146 (2006)
特集1：アデノウイルスを用いた薬物代謝研究
永田 清，金 恵枝
News Letter "Daiichi" , Spring No. 8, pp2-5 (2006)
Influences of Drugs on the Oxygen Uptake Rate and Biosorption of Activated Sludge
Takeshi Kumagai, Tatsuaki Inoue, Yuichi Mihara, Keiichi Ebina, Katsushi Yokota
Biol. Pharm. Bull., 29, 183-186 (2006)
Synthetic Peptide (P-21) Derived from Asp-Hemolysin Inhibits the Induction of Apoptosis on HUVECs by Lysophosphatidylcholine
Hiromu Tsutsumi, Takeshi Kumagai, Saori Naitoo, Keiichi Ebina, Katsushi Yokota
Biol. Pharm. Bull., 29, 907-910 (2006)
酸化修飾低密度リポタンパク質の生物活性とその活性抑制因子としてのAsp-hemolysinに関する分子生物学的研究
熊谷 健
YAKUGAKU ZASSHI, 126, 955-964 (2006)
Oxidized Low-Density Lipoprotein-Binding Specificity of the Asp-Hemolysin-Related Synthetic Peptides from Aspergillus fumigatus
Takeshi Kumagai, Hiromu Tsutsumi, Norihiro Ogawa, Saori Naito, Keiichi Ebina, Katsushi Yokota, Kiyoshi Nagata
Biol. Pharm. Bull., 29, 2181-2186 (2006)
|
Copyright(C)2003
TOHOKU PHARMACEUTICAL UNIVERSITY All Rights Reserved |
|
|
|
