静岡県立大学薬学部 衛生分子毒性学分野
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
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Original article
  1. R. Shizu, Y. Otsuka, K. Ezaki, C. Ishii, S. Arakawa, Y. Amaike, T. Abe, T. Hosaka, T. Sasaki, Y. Kanno, M, Miyata, Y. Yamazoe, K. Yoshinari: Antiepileptic drug-activated constitutive androstane receptor inhibits peroxisome proliferator-activated receptor α- and peroxisome proliferator-activated receptor γ coactivator 1α-dependent gene expression to increase blood triglyceride levels. Mol Pharmacol, 98, 2020. [ASPET]
  2. K. Kondo, N. Yamada, Y. Suzuki, T. Hashimoto, K. Toyoda, T. Takahashi, A. Kobayashi, S. Sugai, K. Yoshinari: Enhancement of acetaminophen-induced chronic hepatotoxicity in spontaneously diabetic torii (SDT) rats. J Toxicol Sci, 45, 245-260, 2020. [J-STAGE]
  3. Y. Matsuzawa, T. Hosaka, A. Ogaito, K. Yoshinari, Y. Uesawa: Prediction Model of Aryl Hydrocarbon Receptor Activation by a Novel QSAR Approach, DeepSnap-Deep Learning. Molecules, 25, 1317, 2020. [MDPI]
  4. Y. Yamazoe, K. Yoshinari: Prediction of regioselectivity and preferred order of CYP1A1-mediated metabolism: Solving the interaction of human and rat CYP1A1 forms with ligands on the template system. Drug Metab Pharmacokinet, 35, 165-185, 2020. [ScienceDirect]
  5. T. Hosaka, A. Wakatsuki, T. Sasaki, R. Shizu, K. Yoshinari: Construction of a PPARα Reporter Assay System with Drug-Metabolizing Capability. BPB Reports, 3, 7-10, 2020. [PSJ]
  6. M. Watanabe, T. Sasaki, J. Takeshita, M. Kushida, Y. Shimizu, H. Oki, Y. Kitsunai, H. Nakayama, H. Saruhashi, R. Ogura, R. Shizu, T. Hosaka, K. Yoshinari: Application of cytochrome P450 reactivity on the characterization of chemical compounds and its association with repeated-dose toxicity. Toxicol Appl Pharmacol, 388,114854, 2020. [Pubmed]
  1. R. Shizu and K. Yoshinari: Nuclear receptor CAR-mediated liver cancer and its species differences. Expert Opin Drug Metab Toxicol, 16, 343-351, 2020. [Pubmed]
Original article
  1. R. Shizu, K. Yokobori, L. Perera, L. Pedersen, M. Negishi: Ligand induced dissociation of the AR homodimer precedes AR monomer translocation to the nucleus. Sci Rep, 9, 16374, 2019. [Pubmed]
  2. T. Abe, R. Shizu, T. Sasaki, Y. Shimizu, T. Hosaka, S. Kodama, A. Matsuzawa, K. Yoshinari: Functional interaction between PXR and YAP in xenobiotic-dependent liver hypertrophy and drug metabolism. J Pharmacol Exp Ther, 370, 590-601, 2019. doi: 10.1124/jpet.119.258632. [Pubmed]
  3. C. Fujino, Y. Watanabe, S. Sanoh, S. Hattori, H. Nakajima, N. Uramaru, H. Kojima, K. Yoshinari, S Ohta, S. Kitamura: Comparative study of the effect of 17 parabens on PXR-, CAR- and PPARα-mediated transcriptional activation. Food Chem Toxicol, 133, 110792, 2019. doi: 110.1016/j.fct.2019.110792. [Pubmed]
  4. C. Fujino, Y. Watanabe, S. Sanoh, H. Nakajima, N. Uramaru, H. Kojima, K. Yoshinari, S Ohta, S. Kitamura: Activation of PXR, CAR and PPARα, pyrethroid pesticides and the effect of metabolism by rat liver microsomes. Heliyon, 5, e02466, 2019. [Pubmed]
  5. M. Okamura, R. Shizu, T. Hosaka, T. Sasaki, K. Yoshinari: Possible involvement of the competition for the transcriptional coactivator glucocorticoid receptor-interacting protein 1 in the inflammatory signal-dependent suppression of PXR-mediated CYP3A induction in vitro. Drug Metab Pharmacokinet, 34, 272-279, 2019. doi: 10.1016/j.dmpk.2019.04.005. [Pubmed]
  6. Y. Watanabe, S. Hattori, C. Fujino, K. Tachibana, H. Kojima, K. Yoshinari, S. Kitamura: Effects of benzotriazole ultraviolet stabilizers on rat PXR, CAR and PPARα transcriptional activities. Fundam Toxicol Sci, 6, 57-63, 2019. doi.org/10.2131/fts.6.57 [J-STAGE]
  7. Y. Yamazoe, K. Yoshinari: Prediction of regioselectivity and preferred order of metabolisms on CYP1A2-mediated reactions part 3: Difference in substrate specificity of human and rodent CYP1A2 and the refinement of predicting system. Drug Metab Pharmacokinet, 34, 217-232, 2019. doi:doi.org/10.1016/j.dmpk.2019.02.001 [ScienceDirect]
  8. H. Kojima, S. Takeuchi, S. Sanoh, K. Okuda, S. Kitamura, N. Uramary, K. Sugihara, K. Yoshinari: Profiling of bisphenol A and eight its analogues on transcriptional activity via human nuclear receptors. Toxicology, 413, 48-55, 2019. doi.org/10.1016/j.tox.2018.12.001 [Pubmed]
  9. K. Nihira, KI. Nan-Ya, M. Kakumi, Y. Ono, Y. Yoshikawa, T. Ota, M. Hiura, K. Yoshinari: Chimeric Mice With Humanized Livers Demonstrate Human-Specific Hepatotoxicity Caused by a Therapeutic Antibody Against TRAIL-Receptor 2/Death Receptor 5. Toxicol Sci, 167, 190-201, 2019. doi.org/10.1093/toxsci/kfy228 [Pubmed]
  10. T. Kimura, T. Hosaka, T. Nakanishi, O. Aozasa: Long-term cadmium exposure enhances metallothionein-1 induction after subsequent exposure to high concentrations of cadmium in P1798 mouse lymphosarcoma cells. J Toxicol Sci, 44, 309-316, 2019. [Pubmed]
  1. K. Yoshinari: Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis. Biol Pharm Bull, 42, 1243-1252, 2019. [J-STAGE]
  2. 吉成浩一, 永井美香: 創薬に活用可能なin silico手法による酵素誘導評価法 日本薬理学雑誌, 4, 186-191, 2019. [日薬理誌]
Original article
  1. 吉成浩一、佐々木崇光、渡邉美智子、橘内陽子、竹下潤一: 化学物質の反復投与毒性予測手法開発の現状と課題. 日本化学会情報化学部会誌, 36, 47-50, 2018. doi.org/10.11546/cicsj.36.47 [J-STAGE]
  2. R. Shizu, M. Kano, T. Abe, S. Tsuchiya, Y. Shimizu, M. Watanabe, T. Hosaka, T. Sasaki, K. Yoshinari: Screening of industrial and agricultural chemicals for searching a mouse PXR activator using cell-based reporter gene assays. BPB Reports, 1, 11-19, 2018. [PSJ]
  3. K. Todoroki, Y. Kudoh, M. Nakamura, Y. Shimizu, T. Sasaki, H. Otsuki, K. Wada, JZ Min, H. Mizuno, K. Yoshinari, T. Toyo'oka: Sensitive and comprehensive LC-MS/MS analyses of chiral pharmaceuticals and their hepatic metabolites using ovomucoid column. Analytical Sciences, 34, 1011-1015, 2018. doi:doi.org/10.2116/analsci.18SCP05 [J-STAGE]
  4. S. Yoshimaru, R. Shizu, S. Tsuruta, Y. Amaike, M. Kano, T. Hosaka, T. Sasaki, K. Yoshinari: Acceleration of murine hepatocyte proliferation by imazalil through the activation of nuclear receptor PXR. J Toxicol Sci, 43, 443-450, 2018. doi:10.2131/jts.43.443 [J-STAGE]
  5. T. Abe, Y. Amaike, R. Shizu, M. Takahashi, M. Kano, T. Hosaka, T. Sasaki, S. Kodama, A. Matsuzawa, K. Yoshinari: Role of YAP activation in nuclear receptor CAR-mediated proliferation of mouse hepatocytes. Toxicol Sci, 165, 408-419, 2018. doi:doi.org/10.1093/toxsci/kfy149 [Oxford]
  6. M. Nagai, T. Hosaka, M. Satsukawa, K. Yoshinari: Characterization of CYP2C induction in cryopreserved human hepatocytes and its application in the prediction of the clinical consequences of the induction. J Pharm Sci, 107, 2479-2488, 2018. doi:doi.org/10.1016/j.xphs.2018.05.008 [ScienceDirect]
  7. R. Shizu, J. Min, M. Sobhany, LC. Pedersen, S. Mutoh, M. Negishi: Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation. J Biol Chem, 293, 333-344, 2018. doi:10.1074/jbc.M117.806604 [Pubmed]
Original article
  1. R. Shizu, M. Osabe, L. Perera, R. Moore, T. Sueyoshi, M. Negishi: Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation. Mol Cell Biol, 37, pii: e00649-16, 2017. doi:10.1128/MCB.00649-16 [Pubmed]
  2. Y. Aratsu, R. Odagiri, R. Shoji, K. Watanabe, T. Kumagai, S. Shindo, T. Sasaki, K. Nagata: CYP3A4 induction mechanism of polycyclic aromatic hydrocarbons differs from that of rifampicin in PXR binding element. Fundam Toxicol Sci, 2017. doi:doi.org/10.2131/fts.4.229 [J-STAGE]
  3. T. Sasaki, Y. Sato, T. Kumagai, K. Yoshinari, K. Nagata: Effect of health foods on cytochrome P450-mediated drug metabolism. J Pharm Health Care Sci, 3:14, 2017. doi:10.1186/s40780-017-0083-x [Pubmed]
  4. J. Takeshita, H. Nakayama, Y. Kitsunai, M. Tanabe, H. Oki, T. Sasaki, K. Yoshinari: Discriminative models using molecular descriptors for predicting increased serum ALT levels in repeated-dose toxicity studies of rats. Computational Toxicology, 2017. doi:dx.doi.org/10.1016/j.comtox.2017.05.002 [ScienceDirect]
  5. S. Kodama, T. Shimura, H. Kuribayashi, T. Abe, K. Yoshinari: Pregnenolone 16α-carbonitrile ameliorates concanavalin A-induced liver injury in mice independent of the nuclear receptor PXR activation. Toxicol Lett, 2017. doi:10.1016/j.toxlet.2017.02.018 [Pubmed]
  6. S. Liu, T. Taisuke, O. Morita, K. Yoshinari, H. Honda: Discriminating between adaptive and carcinogenic liver hypertrophy in rat studies using logistic ridge regression analysis of toxicogenomic data: The mode of action and predictive models. Toxicol Appl Pharmacol, 2017. doi:dx.doi.org/10.1016/j.taap.2017.01.006 [Pubmed]
  7. 増田茜、増田雅美、中島宏之、小島弘幸、北村繁幸、浦丸直人、保坂卓臣、佐々木崇光、吉成浩一: 肝細胞肥大の毒性学的特徴の解明に向けた農薬のラット反復投与毒性試験結果のデータベース構築. 薬学雑誌, 137, 611-622, 2017. doi: 10.1248/yakushi.16-00259 [Pubmed]
  8. T. Abe, M. Takahashi, M. Kano, Y. Amaike, C. Ishii, K. Maeda, Y. Kudoh, T. Morishita, T. Hosaka, T. Sasaki, S. Kodama, A. Matsuzawa, H. Kojima, K. Yoshinari: Activation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid. Arch Toxicol, 91, 2365-2374, 2017. doi:10.1007/s00204-016-1888-3 [Pubmed]
Original article
  1. Y. Yamazoe, K. Ito, Y. Yamamura, K. Yoshinari: Prediction of regioselectivity and preferred order of metabolisms on CYP1A2-mediated reactions. Part 1. Focusing on polycyclic arenes and the related chemicals. Drug Metab Pharmacokinet, 31, 363-384, 2016. doi:10.1016/j.dmpk.2016.07.005. [Pubmed]
  2. C. Fujino, T. Tamura, S. Tange, H. Nakajima, S. Sanoh, Y. Watanabe, N. Uramaru, H. Kojima, K. Yoshinari, S. Ohta, S, Kitamura: Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities. J Toxicol Sci, 41, 677-691, 2016. doi:10.2131/jts.41.677. [Pubmed]
  3. 熊谷健, 佐々木崇光, 永田清: レポーター遺伝子導入培養細胞を用いた健康食品によるCYP1A1/CYP1A2誘導の網羅的評価. 医療薬学,2016. [J-STAGE]
  4. T. Sasaki, K. Inami, Y. Numata, K. Funakoshi, M. Yoshida, T. Kumagai, S. Matsui, T. Toriyabe, Y. Yamazoe, K. Yoshinari, K. Nagata: : Activation of p38 mitogen-activated protein kinase by clotrimazole induces multidrug resistance-associated protein 3 activation through a novel transcriptional element. J Pharmacol Exp Ther, 359, 102-109, 2016. doi:10.1124/jpet.115.231589. [Pubmed]
  5. M. Nagai, Y. Konno, M. Satsukawa, S. Shinji, K. Yoshinari: Establishment of in silico prediction models for CYP3A4 and CYP2B6 induction in human hepatocytes by multiple regression analysis using azole compounds. Drug Metab Dispos, 44, 1390-1398, 2016. doi:10.1124/dmd.115.068619. [Pubmed]
  6. T. Kumagai, Y. Aratsu, R. Sugawara, T. Sasaki, S. Miyairi, K. Nagata: Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor. Drug Metab Pharmacokinet, 31, 139-145, 2016. doi:10.1016/j.dmpk.2016.01.002. [Pubmed]
  7. M. Kumondai, H. Hosono, K. Orikasa, A. Yoichi, H. Sugimura, S. Ozono, T. Sugiyama, T. Takayama, T. Sasaki, N. Hirasawa. M. Hiratsuka: Genetic Polymorphisms of CYP2A6 in a Case-Control Study on Bladder Cancer in Japanese Smokers. Biol Pharm Bull, 39: 84-89, 2016. doi: http://doi.org/10.1248/bpb.b15-00604. [J-STAGE]
Original article
  1. R. Shizu, T. Abe, S. Benoki, M. Takahashi, S. Kodama, M. Miyata, A. Matsuzawa, K. Yoshinari: PXR stimulates growth factor-mediated hepatocyte proliferation by cross-talk with FOXO transcription factor. Biochem J, 473: 257-266. doi: 10.1042/BJ20150734. [Pubmed]
  2. M. Yoshida, T. Umemura, H. Kojima, K. Inoue, M. Takahashi, N. Uramaru, S. Kitamura, K. Abe, M. Tohkin, S. Ozawa, K. Yoshinari: Basic principles of interpretation of hepatocellular hypertrophy in risk assessment in Japan. Shokuhin Eiseigaku Zasshi, 56: 42-8, 2015. doi: 10.3358/shokueishi.56.42. [Pubmed]
  3. S. Iwamori, E. Sato, D. Saigusa, K. Yoshinari, S. Ito, H. Sato, N. Takahashi: A novel and sensitive assay for heme oxygenase activity. Am J Physiol Renal Physiol, 309: F667-71, 2015. doi: 10.1152/ajprenal.00210.2015. [Pubmed]
  4. Y. Sato, T. Sasaki, S. Takahashi, T. Kumagai, K. Nagata*: Development of a highly reproducible system to evaluate inhibition of cytochrome P450 3A4 activity by natural medicines. J Pharm Pharm Sci, 18: 316-27, 2015.
  5. M. Miyata*, K. Hayashi, H. Yamakawa , Y. Yamazoe, K. Yoshinari: Antibacterial drug treatment increases intestinal bile acid absorption via elevated levels of ileal apical sodium-dependent bile acid transporter but not organic solute transporter α protein. Biol Pharm Bull, 38: 493-6, 2015. doi: 10.1248/bpb.b14-00640. [Pubmed]
  6. H. Hosono, M. Kumondai, T. Arai, H. Sugimura, T. Sasaki, N. Hirasawa, M. Hiratsuka*: CYP2A6 genetic polymorphism is associated with decreased susceptibility to squamous cell lung cancer in Japanese smokers. Drug Metab Pharmacokinet, 30: 263-8, 2015. doi: 10.1016/j.dmpk.2015.04.002. [Pubmed]
  7. K. Inami, T. Sasaki, T. Kumagai, K. Nagata*: Simultaneous evaluation of human CYP3A4 and ABCB1 induction by reporter assay in LS174T cells, stably expressing their reporter genes. Biopharm Drug Dispos, 36: 139-147, 2015. doi: 10.1002/bdd.1927. [Pubmed]
Original article
  1. M. Miyata*, T. Hata, Y. Yamazoe and K. Yoshinari: SREBP-2 negatively regulates FXR-dependent transcription of FGF19 in human intestinal cells. Biochem Biophys Res Commun, 443: 477-82, 2014. doi: 10.1016/j.bbrc.2013.11.126. [Pubmed]
  2. X. Fang, T. Nunoshiba, M. Yoshida, A. Nishikawa, K. Nemoto, M. Degawa, S. Arimoto, K. Okamoto, E. Takahashi, T. Negishi*: Effects of oral administration of non-genotoxic hepato-hypertrophic compounds on metabolic potency of rat liver. Genes and Environment, 36: 1-9, 2014. doi: 10.3123/jemsge.2013.011. [J-STAGE]
  3. Y. Kondo, T. Iwao, K. Nakamura, T. Sasaki, S. Takahashi, N. Kamada, T. Matsubara, FJ Gonzalez, H. Akutsu, Y. Miyagawa, H. Okita, N. Kiyokawa, M. Toyoda, A. Umezawa, K. Nagata, T. Matsunaga*, S. Ohmori: An efficient method for differentiation of human induced pluripotent stem cells into hepatocyte-like cells retaining drug metabolizing activity. Drug Metab Pharmacokinet, 29: 237-43, 2014. doi: 10.2133/dmpk.DMPK-13-RG-104. [Pubmed]
  4. M. Kojima, M. Degawa*: Sex differences in the constitutive gene expression of sulfotransferases and UDP-glucuronosyltransferases in the pig liver: androgen-mediated regulation. Drug Metab Pharmacokinet, 29: 192-7, 2014. doi: 10.2133/dmpk.DMPK-13-RG-086. [Pubmed]
  5. Y. Mirokuji, H. Abe, H. Okamura, K. Saito, F. Sekiya, S. Hayashi, S. Maruyama, A. Ono, M. Nakajima, M. Degawa, S. Ozawa, M. Shibutani*, T. Maitani: The JFFMA assessment of flavoring substances structurally related to menthol and uniquely used in Japan. Food Chem Toxicol, 64, 314-21, 2014. doi: 10.1016/j.fct.2013.11.044. [Pubmed]
  6. Y. Kato, K. Haraguchi, M. Onishi, S. Ikushiro, T. Endo, C. Ohta, N. Koga, S. Yamada, M. Degawa*: 3,3',4,4'-Tetrachlorobiphenyl-mediated decrease of serum thyroxine level in C57BL/6 and DBA/2 mice occurs mainly through enhanced accumulation of thyroxine in the liver. Biol Pharm Bull, 37, 504-9, 2014. doi: 10.1248/bpb.b13-00775. [Pubmed]
  7. M.Z. Ferdaus, B. Xiao, H. Ohara*, K. Nemoto, Y. Harada, K. Saar, N. Hubner, M. Isomura, T. Nabika: Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat. PLOS ONE, 9, e95091, 2014. doi:10.1371/journal.pone.0095091. [Pubmed]
  8. J. Kimura, K. Nemoto, M. Degawa, A. Yokosuka, Y. Mimaki, K. Shimizu, N. Oku, Y. Ohizumi*: Upregulation of N-methyl-D-aspartate receptor subunits and c-Fos expressing genes in PC12D cells by nobiletin. Biol Pharm Bull, 37, 1555-8, 2014. doi: 10.1248/bpb.b14-00177. [Pubmed]
  9. Y. Kumagai, M Sekimoto*, M. Okamoto, R. Kurita, M. Kojima, M. Degawa: Involvement of Hepatic IL-1 in the Strain-Dependent Sex Differences in Serum Total Cholesterol Levels in Rats. Biol Pharm Bull, 37, 654-8, 2014. doi: 10.1248/bpb.b13-00982. [Pubmed]
  10. A. Ikeda, S. Miyata, A. Yokosuka, Y. Mimaki, Y. Ohizumi, M. Degawa, K. Nemoto*: Estimation of endoplasmic reticulum stress-inducing ability of nobiletin, a citrus polymethoxyflavonoid, in SK-N-SH human neuroblastoma cells. Fund Toxicol Sci, 1, 169-72, 2014. doi: 10.2131/fts.1.169. [J-STAGE]
  11. 佐々木崇光, 熊谷健, 佐々木瞳, 稲見敬太, 佐藤裕, 橋昌悟, 松永民秀, 頭金正博, 細川正清, 大森栄, 永田清*: 調剤薬局来局者を対象とした健康食品の使用実態調査とその情報に基づいたCYP2D6活性阻害評価. 医療薬学, 40: 488-99, 2014. [J-STAGE]
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