研究業績

[原著論文]

2022年


• Lee JS, Kawai YK, Morita Y, Covaci A, Kubota A. (2022) Estrogenic and growth inhibitory responses to organophosphorus flame retardant metabolites in zebrafish embryos. Comparative biochemistry and physiology. Part C in press.
  

2021年


• Ishibashi H, Uchida M, Hirano M, Hayashi T, Yamamoto R, Kubota A, Ichikawa N, Ishibashi Y, Tominaga N, Arizono K. (2021) In vivo and in silico analyses of estrogenic potential of equine estrogens in medaka (Oryzias latipes). Sci Total Environ 767, 144379.
  

2020年


• Nakayama, SMM., Morita, A., Ikenaka, Y., Kawai, YK., Watanabe, KP., Ishii, C., Mizukawa, H., Yohannes, YB,, Saito, K., Watanabe, Y., Ito, M., Ohsawa, N., Ishizuka, M. (2020) Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1. Comparative biochemistry and physiology. Part C 228, 108635 (10 pages)
  
• Lee, JS., Morita, Y., Kawai, YK., Covaci, A., Kubota, A. (2020) Developmental circulatory failure caused by metabolites of organophosphorus flame retardants in zebrafish, Danio rerio. Chemosphere 246, 125738 (7 pages).
  
• Kawai, YK., Itou, K., Yoshino, T., Iima, H., Matsumoto, F., Kubota, A. (2020) Hepatic transcriptional profile and tissue distribution of cytochrome P450 1-3 genes in the red-crowned crane Grus japonensis. Comparative biochemistry and physiology. Part C 228, 108643 (9 pages).
  

2019年


• Kondoh, D., Kitayama, C., Yamaguchi, Y., Yanagawa, M., Kawai, YK., Suzuki, C., Itakura, R., Fujimoto, A., Satow, T., Kondo, S., Sato, T. (2019) Nasal cavity of green sea turtles contains three independent sensory epithelia. Chemical Senses doi: 10.1093/chemse/bjz033. [Epub ahead of print].
  
• Kubota, A., Kawai, YK., Yamashita, N., Lee, J. S., Kondoh, D., Zhang, S., Nishi, Y., Suzuki, K., Kitazawa, T., Teraoka, H. (2019) Transcriptional profiling of cytochrome P450 genes in the liver of adult zebrafish, Danio rerio. The Journal of Toxicological Sciences 44, 345-356.
  
• Kawai, YK.*, Shinya, S.*, Ikenaka, Y., Saengtienchai, A., Kondo, T., Darwish, WS., Nakayama, SMM., Mizukawa, H., Ishizuka, M. (2019) Characterization of function and genetic feature of UDP-glucuronosyltransferase in avian species. Comparative biochemistry and physiology. Part C 217, 5-14. * Equal contribution.
  

2018年


• Saengtienchai, A., Ikenaka, Y., Kawata, M., Kawai, Y., Takeda, K., Kondo, T., Bortey-Sam, N., Nakayama, SMM., Mizukawa, H., Ishizuka, M. (2018) Comparison of xenobiotic metabolism in phase I oxidation and phase II conjugation between rats and bird species. Comparative biochemistry and physiology. Part C 214, 28-35.
  
• Kawai, YK., Ikenaka, Y., Ishizuka, M., Kubota, A. (2018) The evolution of UDP-glycosyl/glucuronosyltransferase 1E (UGT1E) genes in bird lineages is linked to feeding habits but UGT2 genes is not. PLoS One e0205266.
  

2017年


• Yin, G., Cao, L., Du, J., Jia, R., Kitazawa, T., Kubota, A., Teraoka, H. (2017) Dexamethasone-induced hepatomegaly and steatosis in larval zebrafish. The Journal of Toxicological Sciences 42, 455-459.
  
• Kondo, T., Ikenaka, Y., Nakayama, SM., Kawai, YK., Mizukawa, H., Nomiyama, K., Tanabe, S., Ishizuka, M. (2017) Uridine Diphosphate-Glucuronosyltransferase (UGT) 2B Subfamily Interspecies Differences in Carnivores. Toxicological Sciences 158, 90-100.
  

2016年


• Nijoukubo, D., Tanaka, Y., Okuno, Y., Yin, G., Kitazawa, T., Peterson, R. E., Kubota, A., Teraoka, H. (2016) Protective effect of prostacyclin against pre-cardiac edema caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin and a thromboxane receptor agonist in developing zebrafish. Chemosphere 156, 111-117.
  
• Wincent, E., Kubota, A., Timme-Laragy, A. R., Jonsson, M. E., Hahn, M. E., Stegeman, J. J. (2016) Biological effects of 6-formylindolo[3,2-b]carbazole (FICZ) in vivo are enhanced by loss of CYP1A function in an Ahr2-dependent manner. Biochemical Pharmacology 110-111, 117-129.
  
• Lemaire, B., Kubota, A., O'Meara, C. M., Lamb, D. C., Tanguay, R. L., Goldstone, J. V., Stegeman, J. J. (2016) Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders. Toxicology and Applied Pharmacology 296, 73-84.
  
• Saengtienchai, A., Ikenaka, Y., Bortey-Sam, N., Jermnark, U., Mizukawa, H., Kawai, YK., Nakayama, SM., Ishizuka, M. (2016) The African hedgehog (Atelerix albiventris): Low phase I and phase II metabolism activities. Comparative biochemistry and physiology. Part C 190, 38-47.
  
• Nakayama, SM., Ikenaka, Y., Hayami, A., Mizukawa, H., Darwish, WS., Watanabe, KP., Kawai, YK., Ishizuka, M. (2016) Characterization of equine cytochrome P450: role of CYP3A in the metabolism of diazepam. Journal of veterinary pharmacology and therapeutics 39, 478-87.
  
• Nishiyama, Y., Nakayama, SM., Watanabe, KP., Kawai, YK., Ohno, M., Ikenaka, Y., Ishizuka, M. (2016) Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats. The Journal of veterinary medical science 78, 675-680.
  

2015年


• Mizukawa, H., Nomiyama, K., Nakatsu, S., Iwata, H., Yoo, J., Kubota, A., Yamamoto, M., Ishizuka, M., Ikenaka, Y., Nakayama, S., Kunisue, T., Tanabe, S. (2015) Organohalogen compounds in pet dog and cat: Do pets biotransform natural brominated products in food to harmful hydroxlated substances? Environmental Science and Technology 50, 444-452.
  
• Stegeman, J. J. Behrendt, L., Woodin B. R., Kubota, A., Lemaire, B., Pompon, D., Goldstone, J. V., Urban, P. (2015) Functional characterization of zebrafish cytochrome P450 1 family proteins expressed in yeast. Biochimica et Biophysica Acta General Subjects 1850, 2340-2352.
  
• Kubota, A., Goldstone, J. V., Lemaire, B., Takata, M., Woodin, B. R., Stegeman, J. J. (2015) Role of pregnane X receptor and aryl hydrocarbon receptor in transcriptional regulation of pxr, CYP2, and CYP3 genes in developing zebrafish. Toxicological Sciences 143, 398-407.
  
• Okamatsu, G., Komatsu, T., Kubota, A., Onaga, T., Uchide, T., Endo, D., Kirisawa, R., Yin, G., Inoue, H., Kitazawa, T., Uno, Y., Teraoka, H. (2015) Identification and functional characterization of novel feline cytochrome P450 2A. Xenobiotica 45, 503-510.
  
• Kakehi, M., Ikenaka, Y., Nakayama, SM., Kawai, YK., Watanabe, KP., Mizukawa, H., Nomiyama, K., Tanabe, S., Ishizuka, M. (2015) Uridine Diphosphate-Glucuronosyltransferase (UGT) Xenobiotic Metabolizing Activity and Genetic Evolution in Pinniped Species. Toxicological sciences 147, 360-369.
  
• Iwata, H., Yamaguchi, K., Takeshita, Y., Kubota, A., Hirakawa, S., Isobe, T., Hirano, M., Kim, E.Y. (2015) Enzymatic characterization of in vitro-expressed Baikal seal cytochrome P450 (CYP) 1A1, 1A2, and 1B1: Implication of low metabolic potential of CYP1A2 uniquely evolved in aquatic mammals. Aquatic Toxicology 162, 138-151.
  
• Watanabe, KP., Kawai, YK., Nakayama, SM., Ikenaka, Y., Mizukawa, H., Takaesu, N., Ito, M., Ikushiro, SI., Sakaki, T., Ishizuka, M. (2015) Partial cloning of CYP2C23a genes and hepatic protein expression in eight representative avian species. Journal of veterinary pharmacology and therapeutics 38, 190-195.
  

2014年


• Teraoka, H., Okuno, Y., Nijoukubo, D., Yamakoshi, A., Peterson, R. E., Stegeman, J. J., Kitazawa, T., Hiraga, T., Kubota, A. (2014) Involvement of COX2-thromboxane pathway in TCDD-induced precardiac edema in developing zebrafish. Aquatic Toxicology 154, 19-26.
  
• Morrison, A. M. S., Goldstone, J. V., Lamb, D. C., Kubota, A., Lemaire, B., Stegeman, J. J. (2014) Identification, modeling and ligand affinity of early deuterostome CYP51s, and functional characterization of recombinant zebrafish sterol 14α-demethylase. Biochimica et Biophysica Acta General Subjects 1840, 1825-1836.
  

2013年


• Bainy, A. C. D.*, Kubota, A.*, Goldstone, J. V., Lille-Langoy, R., Karchner, S. I., Hahn, M. E., Goksoyr, A., Stegeman, J. J. (2013) Functional characterization of a full length pregnane-X-receptor, expression in vivo, and identification of PXR alleles in zebrafish (Danio rerio). Aquatic Toxicology, 142-143, 447-457. * Equal contribution.
  
• Kubota, A.*, Bainy, A. C. D.*, Woodin, B. R., Goldstone, J. V., Stegeman, J. J. (2013) The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): Expression of Cyp2aa1 and Cyp2aa2 and response to phenobarbital-type inducers. Toxicology and Applied Pharmacology 272, 172-179. * Equal contribution.
  
• Thuruthippallil, L. M., Kubota, A., Kim, E.-Y., Iwata, H. (2013) Alternative in vitro approach for assessing AHR-mediated CYP1A induction by dioxins in wild cormorant (Phalacrocorax carbo) population. Environmental Science and Technology 47, 6656-6663.
  
• Kubota, A., Yoneda, K., Tanabe, S., Iwata, H. (2013) Sex differences in the accumulation of chlorinated dioxins in the cormorant (Phalacrocorax carbo): implication of hepatic sequestration in the maternal transfer. Environmental Pollution 178, 300-305.
  
• Watanabe, KP.*, Kawai, YK.*, Ikenaka, Y., Kawata, M., Ikushiro, SI., Sakaki, T., Ishizuka, M. (2013) Avian Cytochrome P450 (CYP) 1-3 Family Genes: Isoforms, Evolutionary Relationships, and mRNA Expression in Chicken Liver. PloS one 8, e75689. * Equal contribution.
  
• Fujisawa, N., Kawai, YK., Nakayama, SM., Ikenaka, Y., Yamamoto, H., Ishizuka, M. (2013) Dioxin Sensitivity-Related Two Critical Amino Acids of Arylhydrocarbon Receptor May Not Correlate with the Taxonomy or Phylogeny in Avian Species. The Journal of veterinary medical science 75, 1577-1583.
  
• Kawai Y,K., Watanabe, KP., Ishii, A., Ohnuma, A., Sawa, H., Ikenaka, Y., Ishizuka, M. (2013) De novo sequence analysis of cytochrome P450 1-3 genes expressed in ostrich liver with highest expression of CYP2G19. Comparative biochemistry and physiology. Part D 8, 201-208.
  
• Tanaka, KD., Kawai, YK., Ikenaka, Y., Harunari, T., Tanikawa, T., Fujita, S., Ishizuka, M. (2013) A novel mutation in VKORC1 and its effect on enzymatic activity in Japanese warfarin-resistant rats. The Journal of veterinary medical science 75, 135-139.
  

2012年


• Jonsson, M. E.*, Kubota, A.*, Timme-Laragy, A. R., Woodin, B. R., Stegeman, J. J. (2012) Ahr2-dependance of PCB126 effects on the swimbladder in relation to expression of CYP1 and cox-2 genes in developing zebrafish. Toxicology and Applied Pharmacology 265, 166-174. * Equal contribution.
  
• Kubota, A., Watanabe, M. X., Kim, E.-Y., Yoneda, K., Tanabe, S., Iwata, H. (2012) Accumulation of dioxins and induction of cytochrome P450 1A4/1A5 enzyme activities in common cormorants from Lake Biwa, Japan: Temporal trends and validation of national regulation on dioxins emission. Environmental Pollution 168, 131-137.
  
• Teraoka, H., Ito, S., Ikeda, H., Kubota, A., Elmagd, M. M. A., Kitazawa, T., Kim, E. Y., Iwata, H., Endoh, D. (2012) Differential display system with vertebrate-common degenerate oligonucleotide primers: uncovering genes responsive to dioxin in avian embryonic liver. Environmental Science and Technology 46, 27-33.
  
• M'kandawire, E., Syakalima, M., Muzandu, K., Pandey, G., Simuunza, M., Nakayama, SM., Kawai, YK., Ikenaka, Y., Ishizuka, M. (2012) The nucleotide sequence of metallothioneins (MT) in liver of the Kafue lechwe (Kobus leche kafuensis) and their potential as biomarkers of heavy metal pollution of the Kafue River. Gene 506, 310-316.
  
• Tanaka, KD., Kawai, YK., Ikenaka, Y., Harunari, T., Tanikawa, T., Ando, S., Min, H., Okajima, F., Fujita, S., Ishizuka, M. (2012) The genetic mechanisms of warfarin resistance in Rattus rattus found in the wild in Japan. Pesticide Biochemistry and Physiology 103, 144-151.
  

2011年


• Honda, K., Komatsu, T., Koyama, F., Kubota, A., Kawakami, K., Asakura, H., Uno, Y., Kitazawa, T., Hiraga, T., Teraoka, H. (2011) Expression of two novel cytochrome P450 3A131 and 3A132 in liver and small intestine of domestic cats. The Journal of Veterinary Medical Science 73, 1489-1492.
  
• Kubota, A., Stegeman, J. J., Woodin, B. R., Iwanaga, T., Harano, R., Peterson, R. E., Hiraga, T., Teraoka, H. (2011) Role of zebrafish cytochrome P450 CYP1C genes in the reduced mesencephalic vein blood flow caused by activation of AHR2. Toxicology and Applied Pharmacology 253, 244-252.
  
• Kubota, A., Stegeman, J. J., Goldstone, J. V., Nelson, D. R., Kim, E. Y., Tanabe, S., Iwata, H. (2011) Cytochrome P450 CYP2 genes in the common cormorant: evolutionary relationships with 130 diapsid CYP2 clan sequences and chemical effects on their expression. Comparative Biochemistry and Physiology Part C 153, 280-289.
  

2010年


• Goldstone, J. V., McArthur, A. G., Kubota, A., Zanette, J., Parente, T., Jonsson, M. E., Nelson, D. R., Stegeman, J. J. (2010) Identification and developmental expression of the full complement of cytochrome P450 genes in zebrafish. BMC Genomics 11, 643.
  
• Komatsu, T., Honda, K., Kubota, A., Kitazawa, T., Hiraga, T., Teraoka, H. (2010) Molecular cloning and expression of cytochrome P450 2D6 in the liver of domestic cats. The Journal of Veterinary Medical Science 72, 1633-1636.
  
• Teraoka, H., Ogawa, A., Kubota, A., Stegeman, J. J., Peterson, R. E., Hiraga, T. (2010) Malformation of certain brain blood vessels caused by TCDD activation of Ahr2/Arnt1 signaling in developing zebrafish. Aquatic Toxicology 99, 241-247.
  
• Kubota, A., Watanabe, M., Kunisue, T., Kim, E. Y., Tanabe, S., Iwata, H. (2010) Hepatic CYP1A induction by chlorinated dioxins and related compounds in the endangered black-footed albatross from the North Pacific. Environmental Science and Technology 44, 3559-3365.
  
• Darwish, WS., Kawai, Y., Ikenaka, Y., Yamamoto, H., Muroya, T., Ishizuka, M.. (2010) Identification and phylogenetic analysis of novel cytochrome P450 1A genes from ungulate species. The Journal of veterinary medical science 72, 1237-1241.
  
• Kawai, YK., Ikenaka, Y., Fujita, S., Ishizuka, M. (2016) The CYP1D subfamily of genes in mammals and other vertebrates. Mammalian genome 21, 320-329.
  

2009年以前


• Kubota, A., Kim, E.-Y., Iwata, H. (2009) Alkoxyresorufin (methoxy-, ethoxy-, pentoxy- and benzyloxyresorufin) O-dealkylase activities by in vitro-expressed cytochrome P450 1A4 and 1A5 from common cormorant (Phalacrocorax carbo). Comparative Biochemistry and Physiology Part C 149, 544-551.
  
• Teraoka, H., Kubota, A., Dong, W., Kawai, Y., Yamazaki, K., Mori, C., Harada, Y., Peterson, R. E., Hiraga, T. (2009) Role of the cyclooxygenase 2?thromboxane pathway in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced decrease in mesencephalic vein blood flow in the zebrafish embryo. Toxicology and Applied Pharmacology 234, 33-40.
  
• Kubota, A., Iwata, H., Kim, E.-Y. (2008) Catalytic function of avian cytochrome P450 1A4 and 1A5 (CYP1A4 and CYP1A5) enzymes heterologously expressed using in vitro yeast system. Marine Environmental Research 66, 154-155.
  
• Kubota, A., Iwata, H., Goldstone, H. M. H., Kim, E.-Y., Stegeman, J. J., Tanabe, S. (2006) Cytochrome P450 1A4 and 1A5 in common cormorant (Phalacrocorax carbo): Evolutionary relationships and functional implications associated with dioxin and related compounds. Toxicological Sciences 92, 394-408.
  
• Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S. (2006) Congener-specific toxicokinetics of PCDDs, PCDFs, and coplanar PCBs in black-eared kites, Milvus migrans: CYP1A-dependent hepatic sequestration. Environmental Toxicology and Chemistry 25, 1007-1016.
  
• Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S. (2005) Hepatic CYP1A induction by dioxin-like compounds, and congener-specific metabolism and sequestration in wild common cormorants from Lake Biwa, Japan. Environmental Science and Technology 39, 3611-3619.
  
• Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S. (2004) Levels and toxicokinetic behaviors of PCDD, PCDF, and coplanar PCB congeners in common cormorants from Lake Biwa, Japan. Environmental Science and Technology 38, 3853-3859.
  
• 久保田 彰, 染矢雅之, 渡部真文, 田辺信介. (2002) PCBsおよびダイオキシン類（ポリ塩化ジベンゾ-p-ダイオキシン，ポリ塩化ジベンゾフラン，コプラナPCBs）による宇和海沿岸堆積物の汚染. 日本水産学会誌 68, 695-700.
  

[著書・総説]

• 久保田 彰. 獣医毒性学＜第二版＞. 第14章 内分泌毒性, コラム8. 2020年3月（ISBN: 9784874022603）.
• 川島千帆、久保田　彰. (2018) 十勝の台風被害による飼料用トウモロコシサイレージおよび牧草サイレージのかび毒汚染の実態. 29~33., 北海道畜産草地学会報 6.
• 久保田　彰. (2017) 野生鳥類におけるダイオキシン類のエコトキシコロジー. 63~67, 野生動物医学会誌 22.
• 久保田 彰, 李 鎮善, 金 恩英, 岩田久人. (2011) 第13章 鳥類のエコトキシコロジー: AHRシグナル伝達系の多様性とダイオキシン類のリスク評価. 93~102, ホルモンと臨床, 山田正信企画, 医学の世界社, 東京, 123 p.
• 寺岡宏樹, 久保田 彰. (2009) 第6章 環境衛生 01 野生動物にみられる環境汚染の影響. 106~113, 最新獣医公衆衛生, 田村 豊監修, チクサン出版社, 緑書房, 東京, 174 p.

その他

• 池本 秀樹、沖澤 優花、川合 佑典、一瀬 貴大、池中 良徳、久保田 彰. ゼブラフィッシュを用いたネオニコチノイド系農薬の体内動態と発達神経毒性の解明. 環境ホルモン学会ニュースレター 24(4), p 3-4, 2022年3月.
• Jae Seung Lee, Yusuke K Kawai, Yuri Morita, Adrian Covaci, Akira Kubota. Mechanistic investigation of developmental cardiovascular toxicity caused by organophosphate triesters and their metabolites in zebrafish embryo. 環境ホルモン学会ニュースレター 24(3), p 4, 2022年1月.
• 久保田 彰. 「北海道における毒性学研究」および「受容体原性毒性に関する研究の最前線」の趣旨および概要説明. 環境ホルモン学会ニュースレター 24(3), p 5, 2022年1月.
• 久保田 彰. 発達期ゼブラフィッシュにおけるリン酸エステル系難燃剤の代謝物の発生毒性. 環境ホルモン学会ニュースレター 22(4), p 4, 2020年3月.
• 久保田 彰. ゼブラフィッシュを用いた in silico・in vivo解析によるビスフェノール類および有機リン系難燃剤の生態影響評価と作用機序解明. LaMerニュース 5, p 12-13, 2018年7月.
• 久保田 彰. ゼブラフィッシュをモデルとした魚類PXR‐CYPシグナル伝達機構の解明. 環境ホルモン学会ニュースレター 16(3), p 4, 2013年12月.
• 久保田 彰. SETAC North America 30th annual meeting参加報告記. 環境毒性学会誌. 2009 Dec; 12: 149-152.
• Kubota, A., Iwata, H., Kim, E. Y. (2007) Enzymatic studies of avian cytochrome P450 1A4 and 1A5 isozymes heterologously expressed in yeast cells: analysis of interaction with alkoxyresorufins and 2,3,7,8-TCDF. Organohalogen Compounds 69, 198-201.
• Kubota, A., Iwata, H., Tanabe, S., Yoneda, K., Tobata, S. (2004) Hepatic CYP1A involved in metabolism and sequestration of PCDD, PCDF and coplanar PCB congeners in common cormorants. Organohalogen Compounds 66, 2939-2944.
• Iwata, H., Kim, E. Y., Kubota, A., Watanabe, M., Sakamoto, T., Hirakawa, S., Okamoto, M., Tanabe, S. (2004) Comparative characterization of CYP1As as a biomarker of PCDDs/DFs and Co-PCBs contamination in aquatic birds and mammals. Proceedings of 1st International Symposium on Environmental Behavior and Ecological Impacts of Persistent Toxic Substances 167-172.
• Kubota, A., Iwata, H., Tanabe, S. (2003) Persistent organochlorine contaminants and hepatic cytochrome P450s in common cormorants and black-eared kites. Organohalogen Compounds 64, 391-394.
• 田辺信介, 渡辺倫夫, 久保田 彰, 岩田久人. 東京産ハシブトガラスのダイオキシン類汚染と肝チトクロームP450への影響. 平成14年度野生生物のダイオキシン類蓄積状況及び影響調査報告書. 財団法人自然環境研究センター. 2003; 71-94.
• 田辺信介, 久保田 彰, 渡辺倫夫, 岩田久人. カワウのダイオキシン類汚染と肝チトクロームP450系への影響. 平成14年度野生生物のダイオキシン類蓄積状況及び影響調査報告書. 財団法人自然環境研究センター. 2003; 29-67.
• 田辺信介, 久保田 彰, 岩田久人. 環境データの解析と環境中生物影響評価－生体汚染の実態解明とその影響評価に関する研究－. 環境中複合化学物質による次世代影響リスクの評価とリスク対応支援に関する研究. 環境技術開発等推進事業研究 平成14年度報告書. 環境省. 2003; 89-165.
• 田辺信介, 久保田 彰, 岩田久人. 3-2 薬物代謝酵素の測定. 野生生物のダイオキシン類蓄積状況等調査マニュアル. 財団法人自然環境研究センター. 2002; 130-133.