論文 - 榊原 陽一
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完熟きんかん摂食に伴う血清βクリプトキサンチン濃度の検討-ランダム化非盲検非摂食同時対照群間比較試験- 査読あり
有村 保次, 武安 智樹, 米澤 ゆう子, 永濵 清子, 神力 はるな, 近藤 知巳, 上野 浩晶, 松元 信弘, 江藤 望, 榊原 陽一, 水光 正仁, 片岡 寛章
薬理と治療 47 ( 1 ) 65 - 75 2019年1月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Identification of zebrafish steroid sulfatase and comparative analysis of the enzymatic properties with human steroid sulfatase. 査読あり
Kurogi K, Yoshihama M, Williams FE, Kenmochi N, Sakakibara Y, Suiko M, Liu MC.
Journal of Steroid Biochemistry and Molecular Biology 185 110 - 117 2019年1月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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The critical role of His48 in mouse cytosolic sulfotransferase SULT2A8 for the 7-hydroxyl sulfation of bile acids. 査読あり
Shimohira, T., Kurogi, K., Liu, M.-C., Suiko, M., Sakakibara, Y.
Biosci. Biotechnol. Biochem. 82 1359 - 1365 2018年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Sulfation of catecholamines and serotonin by SULT1A3 allozymes. 査読あり
Bairam, A.F., Rasool, M.I., Alherz, F.A., Abunnaja, M.S., El Daibani, A.A., Gohal, S.A., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
Biochem. Pharmacol. 151 104 - 113 2018年5月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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On the Role of Genetic Polymorphisms in the Sulfation of Cholesterol by Human Cytosolic Sulfotransferase SULT2B1b. 査読あり
Alherz, F.A., El Daibani, A.A., Bairam, A.F., Abunnaja. M.S., Rasool, M.I., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
J. Biochem. 164 215 - 221 2018年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1093/jb/mvy042
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Effects of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and Pregnenolone by Human Cytosolic Sulfotransferase SULT2A1. 査読あり
Abunnaja, M.S.、Alherz, F.A.、El Daibani, A.A.、Bairam, A.F.、Rasool, M.I.、Gohal, S.A.、Kurogi, K.、Suiko, M.、Sakakibara, Y.、Liu, Mi.-C.
Biochem. Cell Biol. 96 655 - 662 2018年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Radical scavenging effects of 1-naphthol, 2-naphthol, and their sulfate-conjugates 査読あり
Sugahara Shintaro, Fukuhara Kumiko, Tokunaga Yuki, Tsutsumi Shuhei, Ueda Yuto, Ono Masateru, Kurogi Katsuhisa, Sakakibara Yoichi, Suiko Masahito, Liu Ming-Cheh, Yasuda Shin
Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｔｏｘｉｃｏｌｏｇｉｃａｌ Ｓｃｉｅｎｃｅｓ 43 ( 3 ) 213 - 221 2018年3月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：一般社団法人 日本毒性学会
1-Naphthol (1-Nap) and 2-naphthol (2-Nap) are phenolic isomers that may be subjected to sulfate conjugation <i>in vivo</i>. Phase-II sulfate conjugation of phenolic compounds is generally thought to result in their inactivation. This study aimed to investigate the antioxidative effects of 1-NapS and 2-NapS, in comparison with their unsulfated counterparts, using established free radical scavenging assays. Based on the calculated EC<sub>50</sub> values, 1-NapS resulted in 5.60 to 7.35-times lower antioxidative activity than 1-Nap. In contrast, 2-NapS showed comparable activities as did the unsulfated 2-Nap. Collectively, the results obtained indicated that sulfate conjugation of the Nap isomers did not always result in the decrease of their antioxidant activity, and the antioxidant activity that remained appeared to depend on the position of sulfation.
DOI： 10.2131/jts.43.213
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Effects of Human SULT2A1 Genetic Polymorphisms on the Sulfation of Tibolone 査読あり
Miller, E., Zalzala, M.H., Abunnaja, M.S., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C.
Eur. J. Drug Metab. Pharmacokinetics 2018年2月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1 査読あり
Tanaka S., Nishiyori T., Kojo H., Otsubo R., Tsuruta M., Kurogi K., Liu M., Suiko M., Sakakibara Y., Kakuta Y.
Scientific Reports 7 ( 1 ) 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Scientific Reports
© 2017 The Author(s). Tyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved. Here, we report two crystal structures of the human TPST1 complexed with two substrate peptides that are catalysed by human TPST1 with significantly different efficiencies. The distinct binding modes found in the two complexes provide insight into the sulfation mechanism for these substrates. The present study provides valuable information describing the molecular mechanism of post-translational protein modifications catalysed by TPSTs.
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完熟きんかん摂食に伴う抗疲労効果の検討—ランダム化非盲検非摂食同時対照比較群間試験— 査読あり
武安智樹、有村保次、永濵清子、神力はるな、榊原陽一、水光正仁、片岡寛章
薬理と治療 45 1967 - 1975 2017年12月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Kurogi K., Yoshihama M., Horton A., Schiefer I., Krasowski M., Hagey L., Williams F., Sakakibara Y., Kenmochi N., Suiko M., Liu M.
Journal of Steroid Biochemistry and Molecular Biology 174 120 - 127 2017年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Steroid Biochemistry and Molecular Biology
© 2017 Elsevier Ltd 5α-Cyprinol 27-sulfate is the major biliary bile salt present in cypriniform fish including the zebrafish (Danio rerio). The current study was designed to identify the zebrafish cytosolic sulfotransferase (Sult) enzyme(s) capable of sulfating 5α-cyprinol and to characterize the zebrafish 5α-cyprinol-sulfating Sults in comparison with human SULT2A1. Enzymatic assays using zebrafish homogenates showed 5α-cyprinol-sulfating activity. A systematic analysis, using a panel of recombinant zebrafish Sults, revealed two Sult2 subfamily members, Sult2st2 and Sult2st3, as major 5α-cyprinol-sulfating Sults. Both enzymes showed higher activities using 5α-cyprinol as the substrate, compared to their activity with DHEA, a representative substrate for mammalian SULT2 family members, particularly SULT2A1. pH-Dependence and kinetics experiments indicated that the catalytic properties of zebrafish Sult2 family members in mediating the sulfation of 5α-cyprinol were different from those of either zebrafish Sult3st4 or human SULT2A1. Collectively, these results imply that both Sult2st2 and Sult2st3 have evolved to sulfate specifically C 27 -bile alcohol, 5α-cyprinol, in Cypriniform fish, whereas the enzymatic characteristics of zebrafish Sult3 members, particularly Sult3st4, correlated with those of human SULT2A1.
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Δ<sup>4</sup>-3-ketosteroids as a new class of substrates for the cytosolic sulfotransferases 査読あり
Hashiguchi T., Kurogi K., Shimohira T., Teramoto T., Liu M., Suiko M., Sakakibara Y.
Biochimica et Biophysica Acta - General Subjects 1861 ( 11 ) 2883 - 2890 2017年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Biochimica et Biophysica Acta - General Subjects
© 2017 Elsevier B.V. Cytosolic sulfotransferase (SULT)-mediated sulfation is generally known to involve the transfer of a sulfonate group from the active sulfate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), to a hydroxyl group or an amino group of a substrate compound. We report here that human SULT2A1, in addition to being able to sulfate dehydroepiandrosterone (DHEA) and other hydroxysteroids, could also catalyze the sulfation of Δ 4 -3-ketosteroids, which carry no hydroxyl groups in their chemical structure. Among a panel of Δ 4 -3-ketosteroids tested as substrates, 4-androstene-3,17-dione and progesterone were found to be sulfated by SULT2A1. Mass spectrometry analysis and structural modeling supported a reaction mechanism which involves the isomerization of Δ 4 -3-ketosteroids from the keto form to an enol form, prior to being subjected to sulfation. Results derived from this study suggested a potential role of SULT2A1 as a Δ 4 -3-ketosteroid sulfotransferase in steroid metabolism.
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疲労感を有する健常人に対する完熟きんかんの有効性を探索する非対照・非盲検試験 査読あり
永濵清子、有村保次、神力はるな、米澤ゆう子、松尾彩子、上野浩晶、松元信弘、江藤望、榊原陽一、水光正仁、片岡寛章
薬理と治療 45 1831 - 1842 2017年11月
記述言語：日本語 掲載種別：研究論文（学術雑誌）
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Identification and characterization of the zebrafish glutathione S-transferase Pi-1
Abunnaja M., Kurogi K., Mohammed Y., Sakakibara Y., Suiko M., Hassoun E., Liu M.
Journal of Biochemical and Molecular Toxicology 31 ( 10 ) 2017年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Biochemical and Molecular Toxicology
© 2017 Wiley Periodicals, Inc. Zebrafish has in recent years emerged as a popular vertebrate model for use in pharmacological and toxicological studies. While there have been sporadic studies on the zebrafish glutathione S-transferases (GSTs), the zebrafish GST gene superfamily still awaits to be fully elucidated. We report here the identification of 15 zebrafish cytosolic GST genes in NCBI GenBank database and the expression, purification, and enzymatic characterization of the zebrafish cytosolic GST Pi-1 (GSTP1). The cDNA encoding the zebrafish GSTP1 was cloned from a 3-month-old female zebrafish, expressed in Eschelichia coli host cells, and purified. Purified GSTP1 displayed glutathione-conjugating activity toward 1-chloro-2,4-dinitrobenzene as a representative substrate. The enzymatic characteristics of the zebrafish GSTP1, including pH-dependency, effects of metal cations, and kinetic parameters, were studied. Moreover, the expression of zebrafish GSTP1 at different developmental stages during embryogenesis, throughout larval development, onto maturity was examined.
DOI： 10.1002/jbt.21948
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食品成分の抗酸化能の複合的評価について 査読あり
近藤 知巳, 上橋 朋佳, 渡辺 朋子, 河野 朝美, 黒木 勝久, 福井 敬一, 水光 正仁, 榊原 陽一
日本食品科学工学会誌 64 ( 9 ) 457 - 463 2017年9月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：社団法人 日本食品科学工学会
近年，食品成分による抗酸化に関する研究は盛んに行われており，抗酸化能を評価する手法についても多くの手法が開発されている．化学反応を用いた評価手法は，簡便な操作で検討できることや特殊な機器を必要としないことなどのメリットがある一方で必ずしも，実際の生体内における抗酸化活性と同等の評価になりえないなどのデメリットがあると言われている．そこで本研究では，比較的簡便に抗酸化能を評価できる化学的手法とより生体条件に近いと考えられる細胞応答を基盤としたルシフェラーゼレポーターアッセイ系による抗酸化ストレス作用を抗酸化能の評価系として用い，食品成分の抗複合的な抗酸化活性の評価の可能性について検討を行った．検討の結果，抗酸化活性の高いポリフェノール類であっても，評価法の選択により抗酸化活性に差が生じることや化学的な評価法とレポーターアッセイのような細胞応答を基盤とした評価法を組み合わせることで，複合的な抗酸化活性の知見を得ることが出来る可能性が示された．今後，食品の抗酸化活性の評価は単に抗酸化活性を有する化合物の有無だけでなく，生体内での抗酸化酵素誘導活性を含む評価をすることで，多角的な抗酸化活性を評価出来る可能性があるのではないかと考えられる．
DOI： 10.3136/nskkk.64.457
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Sulfation of vitamin D3-related compounds: Identification and characterization ofthe responsible human cytosolic sulfotransferases. 査読あり
Kurogi, K., Sakakibara, Y., Suiko M, Liu MC.
FEBS Lett. 591 2417 - 2425 2017年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Shimohira, T., Kurogi, K., Hashiguchi, T., Liu, M-C., Suiko, M., Sakakibara, Y.
Journal of Bioscience and Bioengineering 124 ( 1 ) 84 - 90 2017年7月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Bioscience and Bioengineering
© 2017 The Society for Biotechnology, Japan Dietary polyphenols present in fruits and vegetables have been reported to manifest beneficial health effects on humans. Polyphenol metabolites including their sulfated derivatives have been shown to be biologically active. Primarily due to the difficulty in preparing regiospecific sulfated polyphenols for detailed investigations, the exact functions of sulfated polyphenols, however, remain unclear. The current study aimed to develop a procedure for the regioselective production of sulfated polyphenols using Escherichia coli cells expressing human cytosolic sulfotransferases (SULTs). Two regioisomers of sulfated genistein were produced by E. coli cells expressing human SULT1A3, SULT1C4, or SULT1E1, and purified using Diaion HP20 resin, followed by high pressure liquid chromatography (HPLC). Structural analysis using mass spectrometry (MS) and nuclear magnetic resonance (NMR) revealed that E. coli cells expressing SULT1A3 preferentially produced genistein 4′-sulfate, whereas E. coli cells expressing SULT1C4 preferentially produced genistein 7-sulfate. To improve the bioproductivity, the effects of several factors including the concentrations of glucose and SO 4 2− , and growth temperature were investigated. The bioproduction procedure established in this study will be valuable for the production of regioselective sulfated polyphenols for use in future studies on their biological functions.
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Characterization of a novel allergenic protein from the octocoral Scleronephthya gracillima (Kuekenthal) that corresponds to a new GFP-like family named Akane. 査読あり
Kato, Y., Jimbo, M., Sakakibara, Y., Onizuka, R., Takahashi, T., Matsuhashi, S., Mita, H., Amada, K., Imahara, Y., Tanabe, K., Toda, A., Kamiya, H.
Luminescence 2017年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Takao H., Takao H., Hirabayashi K., Nishigaya Y., Kouriki H., Nakaniwa T., Hagiwara Y., Harada J., Sato H., Yamazaki T., Sakakibara Y., Suiko M., Asada Y., Takahashi Y., Yamamoto K., Fukuyama K., Fukuyama K., Sugishima M., Wada K.
Nature Communications 8 2017年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Nature Communications
© The Author(s) 2017.Biliverdin reductase catalyses the last step in haem degradation and produces the major lipophilic antioxidant bilirubin via reduction of biliverdin, using NAD(P)H as a cofactor. Despite the importance of biliverdin reductase in maintaining the redox balance, the molecular details of the reaction it catalyses remain unknown. Here we present the crystal structure of biliverdin reductase in complex with biliverdin and NADP+. Unexpectedly, two biliverdin molecules, which we designated the proximal and distal biliverdins, bind with stacked geometry in the active site. The nicotinamide ring of the NADP+ is located close to the reaction site on the proximal biliverdin, supporting that the hydride directly attacks this position of the proximal biliverdin. The results of mutagenesis studies suggest that a conserved Arg185 is essential for the catalysis. The distal biliverdin probably acts as a conduit to deliver the proton from Arg185 to the proximal biliverdin, thus yielding bilirubin.
DOI： 10.1038/ncomms14397
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Tokumaru M., Adachi F., Toda M., Ito-Inaba Y., Ito-Inaba Y., Yazu F., Hirosawa Y., Sakakibara Y., Suiko M., Kakizaki T., Inaba T.
Plant Physiology 173 ( 1 ) 524 - 535 2017年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Plant Physiology
© 2017 American Society of Plant Biologists. All rights reserved.Arabidopsis (Arabidopsis thaliana) GOLDEN2-LIKE (GLK) transcription factors promote chloroplast biogenesis by regulating the expression of photosynthesis-related genes. Arabidopsis GLK1 is also known to participate in retrograde signaling from chloroplasts to the nucleus. To elucidate the mechanism by which GLK1 is regulated in response to plastid signals, we biochemically characterized Arabidopsis GLK1 protein. Expression analysis of GLK1 protein indicated that GLK1 accumulates in aerial tissues. Both tissue-specific and Suc-dependent accumulation of GLK1 were regulated primarily at the transcriptional level. In contrast, norflurazon-or lincomycin-treated gun1-101 mutant expressing normal levels of GLK1 mRNA failed to accumulate GLK1 protein, suggesting that plastid signals directly regulate the accumulation of GLK1 protein in a GUN1-independent manner. Treatment of the glk1glk2 mutant expressing functional GFP-GLK1 with a proteasome inhibitor, MG-132, induced the accumulation of polyubiquitinated GFP-GLK1. Furthermore, the level of endogenous GLK1 in plants with damaged plastids was partially restored when those plants were treated with MG-132. Collectively, these data indicate that the ubiquitin-proteasome system participates in the degradation of Arabidopsis GLK1 in response to plastid signals.
DOI： 10.1104/pp.16.01546