論文 - 榊原 陽一
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細胞質硫酸転移酵素の新たな生理機能 査読あり
黒木 勝久, 榊原 陽一
生化学 97 ( 2 ) 214 - 219 2025年4月
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Iwamoto W., Ikeda T., Nishikawa H., Hirano M., Kinoshita H., Ono M., Kurogi K., Sakakibara Y., Suiko M., Yasuda S.
Bioscience, Biotechnology and Biochemistry 88 ( 9 ) 1081 - 1089 2024年9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：Bioscience, Biotechnology and Biochemistry
Indoxyl sulfate (IS), a uremic toxin, is a physiologically active sulfated metabolite, specifically in kidney failure patients. Our previous studies have shown that IS downregulates phagocytic immune function in a differentiated HL-60 human macrophage cell model. However, it remains unclear whether IS exerts similar effects on macrophage function in other cell types or in lipopolysaccharide (LPS)-sensitive immune cell models. Therefore, this study aimed to investigate the effects of IS on intracellular oxidation levels and phagocytic activity in a differentiated U937 human macrophage cell model, both in the absence and presence of LPS. Our results demonstrated that IS significantly increases intracellular oxidation levels and decreases phagocytic activity, particularly in cells activated by LPS. Furthermore, we found that 2-acetylphenothiazine, an NADH oxidase inhibitor, attenuates the effects of IS in LPS-activated macrophage cells. Representative antioxidants, trolox, α-tocopherol, and ascorbic acid, significantly mitigated the effects of IS on the macrophages responding to LPS.
DOI： 10.1093/bbb/zbae077
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A new type of sulfation reaction: C-sulfonation for α,β-unsaturated carbonyl groups by a novel sulfotransferase SULT7A1 査読あり
Katsuhisa Kurogi, Yoichi Sakakibara, Takuyu Hashiguchi, Yoshimitsu Kakuta, Miho Kanekiyo, Takamasa Teramoto, Tsuyoshi Fukushima, Takeshi Bamba, Jin Matsumoto, Eiichiro Fukusaki, Hiroaki Kataoka, Masahito Suiko
PNAS Nexas 3 ( 3 ) 097 2024年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Evolution and multiple functions of sulfonation and cytosolic sulfotransferases across species 査読あり
Katsuhisa Kurogi, Masahito Suiko, Yoichi Sakakibara
Bioscience, Biotechnology, and Biochemistry 88 ( 4 ) 368 - 380 2024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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Effects of sturgeon fillet intake on top-ranked Japanese female long-distance runners 査読あり
Haraguchi, Naoki, Nakao, Hiroyuki, Sakakibara, Yoichi, Tamura, Hiroki, Nagahama, Kiyoko, Sakurai, Keiko, Sameshima, Hiroshi, Schauerte, Michael, Ikenoue, Tsuyomu, Katsuragi, Shinji
Journal of Obstetrics and Gynaecology Research 49 ( 8 ) 2164 - 2174 2023年8月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1111/jog.15711
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高速液体クロマトグラフィーを用いたアセトアミノフェン O- 硫酸体とチロシン O- 硫酸体の UV 検出による測定法 査読あり
森田千紘、元山優作、谷口玲央真、上田裕人、木下英樹、小野政輝、黒木勝久、榊原陽一、水光正仁、安田伸
東海大農紀要 42 1 - 8 2023年3月
記述言語：日本語 掲載種別：研究論文（大学，研究機関等紀要）
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チロシン硫酸化研究から食品機能評価など農学分野へのプロテオミクスの応用
榊原 陽一
日本プロテオーム学会誌 7 ( 2 ) 27 - 35 2022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：日本プロテオーム学会
翻訳後修飾としてのチロシン硫酸化はタンパク質の分泌のためのシグナルや活性調節機構として考えられている．我々は長年このチロシン硫酸化に関与する酵素Tyrosylprotein Sulfotransferaseを研究し，その立体構造を解明し基質タンパク質認識機構などに新たな知見を得た．宮崎県地域結集型共同研究事業において，「食の機能を中心としたがん予防基盤技術創出」に関わり，新規食品機能評価技術として，プロテオミクスによるバイオマーカーの探索と定量，情報科学的なニューラルネットワーク解析による機能性推定を組み合わせた革新的な技術を確立した．さらに，タンパク質の修飾と食品機能の関係に着目し，食品の抗酸化作用をタンパク質の酸化傷害レベルを指標に評価するという考えに着想し，タンパク質のカルボニル化や<i>S</i>-ニトロシル化などのレドックスバランスに関連したタンパク質修飾の解析法を開発した．ブランド豚肉，地鶏などの地域の食材のプロテオーム解析や成分分析にも貢献した．
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プロテオミクス基盤技術を活用したブランド豚肉と個体識別の検討
黒木 勝久, 秋山 克樹, 榊原 陽一
電気泳動 66 ( 2 ) 97 - 102 2022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：日本電気泳動学会
黒毛和牛やブランド豚肉を始めとした高付加価値食肉は系統種の交配と飼育条件の工夫により開発される．食肉偽装などの問題もあり，遺伝的・環境的要因を一度に解析できる手法を確立することで，効率的な優良育種とブランド肉の偽装鑑定への応用に期待できる．その一つとして，我々はプロテオミクス基盤技術を活用した解析を行っている．本稿では，豚肉に焦点を当てブランド肉鑑定および優良種豚選抜法への可能性を二次元電気泳動と質量分析計を用いて検討した結果を報告する．プロテオーム解析の結果，ブランド豚肉では解糖系に関するタンパク発現が大きく変動しており，環境要因が糖代謝に与える影響を見出すことが出来たと共に，ブランド豚肉を判別できるマーカータンパク質・ペプチドの候補を見出すことが出来た．さらに，優良育種に用いられるデュロック種と大ヨークシャー種の血清サンプルを用いた解析より，従来の系統的な選抜方法とは異なる新たな個体識別方法への可能性が示された．
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Investigation of radical scavenging effects of acetaminophen, p-aminophenol and their O-sulfated conjugates 国際共著
Morita Chihiro, Tokunaga Yuki, Ueda Yuto, Ono Masateru, Kinoshita Hideki, Kurogi Katsuhisa, Sakakibara Yoichi, Suiko Masahito, Liu Ming-Cheh, Yasuda Shin
The Journal of Toxicological Sciences 47 ( 10 ) 421 - 428 2022年10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：一般社団法人 日本毒性学会
Acetaminophen (APAP) and <i>p</i>-aminophenol (<i>p</i>-AP) are the analogous simple phenolic compounds that undergo sulfate conjugation (sulfation) by cytosolic sulfotransferases. Sulfation is generally thought to lead to the inactivation and disposal of endogenous as well as xenobiotic compounds. This study aimed to investigate the antioxidative effects of <i>O</i>-sulfated form of APAP and <i>p</i>-AP, i.e., APAPS and <i>p</i>-APS, in comparison with their unsulfated counterparts. Using a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay, the antioxidant capacity of APAPS was shown to be approximately 126-times lower than that of APAP. In contrast, <i>p</i>-APS displayed comparable activity as unsulfated <i>p</i>-AP. Similar trends concerning the suppressive effects of these chemicals on cellular O<sub>2</sub><sup>-</sup> radical generation were found using an activated granulocytic neutrophil cell model. Collectively, these results indicated that, depending on the presence of an additional “active site”, sulfation may not always decrease the antioxidant activities of phenolic compounds.
DOI： 10.2131/jts.47.421
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Kurogi K., Cao Y., Segawa K., Sakakibara Y., Suiko M., Uetrecht J., Liu M.C.
Biochemical Pharmacology 204 2022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：Biochemical Pharmacology
Nevirapine (NVP) is an effective drug for the treatment of HIV infections, but its use is limited by a high incidence of severe skin rash and liver injury. 12-Hydroxynevirapine (12-OH-NVP) is the major metabolite of nevirapine. There is strong evidence that the sulfate of 12-OH-NVP is responsible for the skin rash. While several cytosolic sulfotransferases (SULTs) have been shown to be capable of sulfating 12-OH-NVP, the exact mechanism of sulfation in vivo is unclear. The current study aimed to clarify human SULT(s) and human organs that are capable of sulfating 12-OH-NVP and investigate the metabolic sulfation of 12-OH-NVP using cultured HepG2 human hepatoma cells. Enzymatic assays revealed that of the thirteen human SULTs, SULT1A1 and SULT2A1 displayed strong 12-OH-NVP-sulfating activity. 1-Phenyl-1-hexanol (PHHX), which applied topically prevents the skin rash in rats, inhibited 12-OH-NVP sulfation by SULT1A1 and SULT2A1, implying the involvement of these two enzymes in the sulfation of 12-OH-NVP in vivo. Among five human organ cytosols analyzed, liver cytosol displayed the strongest 12-OH-NVP-sulfating activity, while a low but significant activity was detected with skin cytosol. Cultured HepG2 cells were shown to be capable of sulfating 12-OH-NVP. The effects of genetic polymorphisms of SULT1A1 and SULT2A1 genes on the sulfation of 12-OH-NVP by SULT1A1 and SULT2A1 allozymes were investigated. Two SULT1A1 allozymes, Arg37Asp and Met223Val, showed no detectable 12-OH-NVP-sulfating activity, while a SULT2A1 allozyme, Met57Thr, displayed significantly higher 12-OH-NVP-sulfating activity compared with the wild-type enzyme. Collectively, these results contribute to a better understanding of the involvement of sulfation in NVP-induced skin rash and provide clues to the possible role of SULT genetic polymorphisms in the risk of this adverse reaction.
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Yamamoto K., Yamada N., Endo S., Kurogi K., Sakakibara Y., Suiko M.
PLoS ONE 17 ( 8 August ) 2022年8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：PLoS ONE
Polyphenols in plants are important for defense responses against microorganisms, insect herbivory, and control of feeding. Owing to their antioxidant, anti-cancer, and anti-inflammatory activities, their importance in human nutrition has been acknowledged. However, metabolism of polyphenols derived from mulberry leaves in silkworms (Bombyx mori) remains unclear. Sulfotransferases (SULT) are involved in the metabolism of xenobiotics and endogenous compounds. The purpose of this study is to investigate the metabolic mechanism of polyphenols mediated by B. mori SULT. Here, we identified a novel SULT in silkworms (herein, swSULT ST3). Recombinant swSULT ST3 overexpressed in Escherichia coli effectively sulfated polyphenols present in mulberry leaves. swSULT ST3 showed high specific activity toward genistein among the polyphenols. Genistein-7-sulfate was produced by the activity of swSULT ST3. Higher expression of swSULT ST3 mRNA was observed in the midgut and fat body than in the hemocytes, testis, ovary, and silk gland. Polyphenols inhibited the aldo-keto reductase detoxification of reactive aldehydes from mulberry leaves, and the most noticeable inhibition was observed with genistein. Our results suggest that swSULT ST3 plays a role in the detoxification of polyphenols, including genistein, and contributes to the effects of aldo-keto reductase in the midgut of silkworms. This study provides new insight into the functions of SULTs and the molecular mechanism responsible for host plant selection in lepidopteran insects.
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Acetaminophen 硫酸体の有機合成 査読あり
森田千紘、谷口玲央真、吉田実央、德永祐希、木下英樹＊、小野政輝、黒木勝久、榊原陽一、水光正仁、安田伸
東海大農紀要 41 39 - 46 2022年3月
記述言語：日本語 掲載種別：研究論文（大学，研究機関等紀要）
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Molecular cloning and characterization of common marmoset SULT1C subfamily members that catalyze the sulfation of thyroid hormones. 査読あり
Kurogi, K., Manabe, Y., Liu, M.-C., Suiko, M., Sakakibara, Y.
Biosci. Biotechnol. Biochem. 85 2113 - 2120 2021年8月
担当区分：最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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The crystal structure of mouse SULT2A8 reveals the mechanism of 7α-hydroxyl, bile acid sulfation
Teramoto T., Nishio T., Kurogi K., Sakakibara Y., Kakuta Y.
Biochemical and Biophysical Research Communications 562 15 - 20 2021年7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：Biochemical and Biophysical Research Communications
Bile acids play essential roles in facilitating the intestinal absorption of lipophilic nutrients as well as regulation of glucose, lipid, and energy homeostasis via activation of some receptors. Bile acids are cytotoxic, and consequently their concentrations are tightly controlled. A critical pathway for bile acid elimination and detoxification is sulfation. The pattern of bile acid sulfation differs by species. Sulfation preferentially occurs at the 3α-OH of bile acids in humans, but at the 7α-OH in mice. A recent study identified mouse cytosolic sulfotransferase 2A8 (mSULT2A8) as the major hepatic 7α-hydroxyl bile acid-sulfating enzyme. To elucidate the 7α-OH specific sulfation mechanism of mSULT2A8, instead of 3α-OH specific sulfation in humans, we determined a crystal structure of mSULT2A8 in complex with cholic acid, a major bile acid, and 3′-phosphoadenosine-5′-phosphate, the sulfate donor product. Our study shows that bile acid-binding mode of mSULT2A8 and how the enzyme holds the 7α-OH group of bile acids at the catalytic center, revealing that the mechanism underlying 7α-OH specific sulfation. The structure shows the substrate binds to mSULT2A8 in an orientation perpendicular to that of human 3α-hydroxyl bile acid-sulfotransferase (hSULT2A1). The structure of the complex provides new insight into species different bile acid metabolism.
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Proteolytic maturation of the Outer Membrane c-type cytochrome OmcZ by Subtilisin-like Serine Protease is Essential for Optimal Current Production by Geobacter sulfurreducens 査読あり
Kai A, Tokuishi T, Fujikawa T, Kawano Y, Ueki T, Nagamine M, Sakakibara Y, Suiko M, Inoue K.
Appl Environ Microbiol. AEM.02617-20 2021年4月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1128/AEM.02617-20
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Varietal differences in flavonoid and antioxidant activity in Japanese soybean accessions 査読あり
Arifin, H.A, Hashiguchi, T, Nagahama, K, Hashiguchi, M., Muguerza, M., Sakakibara, Y., Tanaka, H., Akashi, R.
Bioscience, biotechnology, and biochemistry 85 ( 4 ) 916 - 922 2021年3月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Effects of indole and indoxyl on the intracellular oxidation level and phagocytic activity of differentiated hl-60 human macrophage cells 査読あり
Tsutsumi, S, Tokunaga, Y, Shimizu, S, Kinoshita, H., Ono, M., Kurogi, K, Sakakibara, Y, Suiko, M, Liu, M.-C, Yasuda, S
Journal of Toxicological Sciences 45 ( 9 ) 569 - 579 2020年9月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Investigation of the effects of indoxyl sulfate, a uremic toxin, on the intracellular oxidation level and phagocytic activity using an HL-60-differentiated human macrophage cell model. 査読あり
Tsutsumi, S., Tokunaga, Y., Shimizu, S., Kinoshita, H., Ono, M., Kurogi, K., Sakakibara, Y., Suiko, M., Liu, M.-C., Yasuda, S.
Biosci. Biotechnol. Biochem. 84 1023 - 1029 2020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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Effect of SULT2B1 genetic polymorphisms on the sulfation of dehydroepiandrosterone and pregnenolone by SULT2B1b allozymes 査読あり
Alherz, F.A., El Daibani, A.A., Sakakibara, Y. Suiko, M., Kurogi, K., Liu, M.-C.
Molecular and Cellular Endocrinology 496 110535 2019年10月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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レトルト加工及び保蔵期間が鶏肉のイミダゾールジペプチド含有量に及ぼす影響 査読あり
神力(長友)はるな、近藤知巳、永濵清子、福井敬一、黒木勝久、水光正仁、榊原陽一.
日本食品科学工学会誌 66 210 - 214 2019年6月