Papers - Kinouchi, Kenichiro

リンパ球性下垂体炎に伴う部分的副腎不全に妊娠中のステロイド補償を行い出産した一例

高橋 利奈, 小林 佐紀子, 宮下 和季, 木内 謙一郎, 水谷 洋佑, 押田 卓磨, 小杉 将太郎, 青山 和樹, 竹林 駿太, 水口 雄貴, 田中 守, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  98 ( 1 ) 315 - 315 2022.04

Lead author, Last author, Corresponding author,  ISSN  0029-0661

右副腎にアルドステロン産生細胞クラスターが多発した、原発性アルドステロン症の一例

大友 佑介, 宮下 和季, 小林 佐紀子, 木内 謙一郎, 水谷 洋佑, 高橋 利奈, 杉田 絵里那, 洲之内 真理愛, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  98 ( 1 ) 387 - 387 2022.04

Lead author, Last author, Corresponding author,  ISSN  0029-0661

診断と治療に難渋し最終的に甲状腺全摘術を施行したアミオダロン誘発甲状腺中毒症の1例

川合 未来, 小林 佐紀子, 宮下 和季, 木内 謙一郎, 渡辺 康博, 青山 和樹, 押田 卓磨, 中島 裕也, 小澤 宏之, 勝俣 良紀, 大喜多 肇, 吉村 弘, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  97 ( 5 ) 1150 - 1150 2022.03

Lead author, Last author, Corresponding author,  ISSN  0029-0661

2型糖尿病で通院中に周期性のACTH上昇を指摘され診断に至ったCushing病の1例

加藤 恭介, 宮下 和季, 小林 佐紀子, 木内 謙一郎, 税所 芳史, 横田 健一, 栗原 勲, 目黒 周, 伊藤 裕

肥満研究 ((一社)日本肥満学会)  27 ( Suppl. ) 345 - 345 2022.03

Lead author, Last author, Corresponding author,  ISSN  1343-229X

チアマゾールによる薬剤性血小板減少症が疑われたが中止後も血小板減少が遷延し、特発性血小板減少性紫斑病と診断された1例

青山 和樹, 小林 佐紀子, 宮下 和季, 木内 謙一郎, 永山 愛子, 櫻井 政寿, 杉山 和俊, 佐々木 裕伸, 中島 裕也, 川合 未来, 洲之内 真理愛, 渡辺 康博, 乃村 元子, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  97 ( 5 ) 1139 - 1139 2022.03

Lead author, Last author, Corresponding author,  ISSN  0029-0661

抗甲状腺薬開始2週間後に熱発した高齢初発のバセドウ病患者の一例

渡辺 康博, 小林 佐紀子, 宮下 和季, 木内 謙一郎, 洲之内 真理愛, 青山 和樹, 川合 未来, 中島 裕也, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  97 ( 5 ) 1142 - 1142 2022.03

Lead author, Last author, Corresponding author,  ISSN  0029-0661

DNA repair factor KAT5 prevents ischemic acute kidney injury through glomerular filtration regulation

Akihito Hishikawa, Kaori Hayashi, Akiko Kubo, Kazutoshi Miyashita, Akinori Hashiguchi, Kenichiro Kinouchi, Norifumi Yoshimoto, Ran Nakamichi, Riki Akashio, Erina Sugita, Tatsuhiko Azegami, Toshiaki Monkawa, Makoto Suematsu, Hiroshi Itoh

iScience (Elsevier BV)  24 ( 12 ) 103436 - 103436 2021.12

Lead author, Last author, Corresponding author,  ISSN  2589-0042

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The "preconditioning effect" in AKI is a phenomenon in which an episode of ischemia-reperfusion results in tolerance to subsequent ischemia-reperfusion injury. However, its relationship between DNA damage repair has not been elucidated. Here, we show the role of KAT5 in the preconditioning effect. Preconditioning attenuated DNA damage in proximal tubular cells with elevated KAT5 expression. Ischemia-reperfusion (IR) injuries were exacerbated, and preconditioning effect vanished in proximal tubular-cell-specific KAT5 knockout mice. Investigation of tubuloglomerular feedback (TGF) by MALDI-IMS and urinary adenosine revealed that preconditioning caused attenuated TGF at least in part via KAT5. In addition, K-Cl cotransporter 3 (KCC3) expression decreased in damaged proximal tubular cells, which may be involved in accelerated TGF following IR. Furthermore, KAT5 induced KCC3 expression by maintaining chromatin accessibility and binding to the KCC3 promoter. These results suggest a novel mechanism of the preconditioning effect mediated by the promotion of DNA repair and attenuation of TGF through KAT5.

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副腎動脈造影と分枝選択的副腎静脈サンプリングにより診断に至ったアルドステロン産生腺腫の1例

西川 賢, 宮下 和季, 小林 佐紀子, 木内 謙一郎, 武田 利和, 田村 全, 中塚 誠之, 水谷 洋佑, 大友 佑介, 青山 和樹, 横田 健一, 栗原 勲, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  97 ( 4 ) 765 - 765 2021.12

Lead author, Last author, Corresponding author,  ISSN  0029-0661

膵癌に対するGEM投与によりTMAを発症した1例

竹原 与優, 安達 京華, 鳥光 拓人, 木内 謙一郎, 山口 慎太郎, 神田 武志, 門川 俊明, 伊藤 裕

日本内科学会関東地方会 (日本内科学会-関東地方会)  673回   38 - 38 2021.11

Lead author, Last author, Corresponding author

Pharmacokinetics of hydrogen after ingesting a hydrogen-rich solution: A study in pigs.

Genki Ichihara, Yoshinori Katsumata, Hidenori Moriyama, Hiroki Kitakata, Akeo Hirai, Mizuki Momoi, Seien Ko, Yoshiki Shinya, Kenichiro Kinouchi, Eiji Kobayashi, Motoaki Sano

Heliyon (Elsevier BV)  7 ( 11 ) e08359 2021.11

Lead author, Last author, Corresponding author, Accepted,  ISSN  24058440

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Drinking hydrogen (H2)-rich water is a common way to consume H2. Although many studies have shown efficacy of drinking H2-rich water in neuropsychiatric and endocrine metabolic disorders, their authenticity has been questioned because none examined the associated pharmacokinetics of H2. Therefore, we performed the first study to investigate the pharmacokinetics of H2 in pigs given an H2-rich glucose solution with the aim to extrapolate the findings to humans. We inserted blood collection catheters into the jejunal and portal veins, suprahepatic inferior vena cava, and carotid artery of 4 female pigs aged 8 weeks. Then, within 2 min we infused 500 ml of either H2-rich or H2-free glucose solution into the jejunum via a percutaneous gastrostomy tube and measured changes in H2 concentration in venous and arterial blood over 120 min. After infusion of the H2-rich glucose solution, H2 concentration in the portal vein peaked at 0.05 mg/L and remained at more than 0.016 mg/L (H2 saturation level, 1%) after 1 h; it also increased after infusion of H2-free glucose solution but remained below 0.001 mg/L (H2 saturation level, 0.06%). We assume that H2 was subsequently metabolized in the liver or eliminated via the lungs because it was not detected in the carotid artery. In conclusion, drinking highly concentrated H2-rich solution within a short time is a good way to increase H2 concentration in portal blood and supply H2 to the liver.

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術後にhungry bone症候群を伴い治療に難渋した副甲状腺癌の一例

杉田 絵里那, 小林 佐紀子, 宮下 和季, 木内 謙一郎, 高橋 利奈, 押田 卓磨, 日鼻 瑛, 小澤 宏之, 関水 真理子, 川井田 みほ, 栗原 勲, 横田 健一, 伊藤 裕

日本内分泌学会雑誌 ((一社)日本内分泌学会)  97 ( 2 ) 521 - 521 2021.10

Lead author, Last author, Corresponding author,  ISSN  0029-0661

【時間生物学の現在】副腎皮質ホルモンの概日リズムと内分泌代謝恒常性

鳥光 拓人, 木内 謙一郎, 栗原 勲, 伊藤 裕

臨床化学 ((一社)日本臨床化学会)  50 ( 4 ) 337 - 344 2021.10

Lead author, Last author, Corresponding author,  ISSN  0370-5633

【時間生物学と医療の融合-現状と将来-】エネルギー代謝・運動の日内ホメオスタシス制御の根幹を成す生体時計

木内 謙一郎, 宮下 和季, 伊藤 裕

Medical Science Digest ((株)ニュー・サイエンス社)  47 ( 8 ) 403 - 407 2021.07

Lead author, Last author, Corresponding author,  ISSN  1347-4340

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概日リズムは生体が昼夜の変化する環境に予測して適応する内分泌代謝恒常性に重要な機構である。その中心的な役割を生体時計が担っており、地球の自転に伴う太陽光の明暗による調節を受けながら、約24時間周期の行動、代謝、ホルモンなどのリズムを生み出している。哺乳類の末梢組織に存在する生体時計は食事や運動にも同調する一方で、食事や運動に対する昼夜の代謝応答を制御することも分かっている。近年の研究で組織や細胞間での時計の連携や協調が、個体のエネルギー代謝恒常性に重要であることも明らかになりつつある。(著者抄録)

濃厚な家族集積性を認める急性発症1型糖尿病の1例

木内 謙一郎, 中島 裕也, 小谷 紀子, 三石 正憲, 税所 芳史, 入江 潤一郎, 田中 正巳, 目黒 周, 伊藤 裕

糖尿病 ((一社)日本糖尿病学会)  64 ( 7 ) 421 - 421 2021.07

Lead author, Last author, Corresponding author,  ISSN  0021-437X

Combined Gene Expression and Chromatin Immunoprecipitation From a Single Mouse Hippocampus.

Jean-Christophe Helbling, Kenichiro Kinouchi, Pierre Trifilieff, Paolo Sassone-Corsi, Marie-Pierre Moisan

Current protocols (Wiley)  1 ( 2 ) e33 2021.02

Lead author, Last author, Corresponding author,  ISSN  26911299

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All neuronal cells hold the same genetic information but vary by their structural and functional plasticity depending on the brain area and environmental influences. Such variability involves specific gene regulation, which is driven by transcription factors (TFs). In the field of neuroscience, epigenetics is the main mechanism that has been investigated to understand the dynamic modulation of gene expression by behavioral responses, stress responses, memory processes, etc. Nowadays, gene expression analyzed by real-time quantitative PCR and TF binding estimated by chromatin immunoprecipitation (ChIP) enables one to dissect this regulation. Because of the wide range of transgenic models, as well as cost-effective aspects, mouse models are widely used neuroscience. Thus, we have set up a protocol that allows extraction of both RNA for gene expression analysis and chromatin for ChIP experiment from a single mouse hippocampus. Using such protocols, information regarding gene expression and regulatory molecular mechanisms from the same animal can be integrated and correlated with neurobiological and behavioral outcomes. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Hippocampus isolation from mouse brain Basic Protocol 2: RNA extraction and gene expression analysis from a mouse half hippocampus Basic Protocol 3: ChIP from one hemisphere side mouse hippocampus.

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エネルギー代謝・運動の日内ホメオスタシス制御の根幹を成す生体時計

Kinouchi Kenichiro

Medical Science Digest 47   403 - 407 2021

Lead author, Last author, Corresponding author

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副腎皮質ホルモンの概日リズムと内分泌代謝恒常性

Kinouchi Kenichiro

臨床化学 50   337 - 344 2021

Lead author, Last author, Corresponding author

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S-adenosyl-l-homocysteine hydrolase links methionine metabolism to the circadian clock and chromatin remodeling.

Carolina Magdalen Greco, Marlene Cervantes, Jean-Michel Fustin, Kakeru Ito, Nicholas Ceglia, Muntaha Samad, Jiejun Shi, Kevin Brian Koronowski, Ignasi Forne, Suman Ranjit, Jonathan Gaucher, Kenichiro Kinouchi, Rika Kojima, Enrico Gratton, Wei Li, Pierre Baldi, Axel Imhof, Hitoshi Okamura, Paolo Sassone-Corsi

Science advances (American Association for the Advancement of Science (AAAS))  6 ( 51 )  2020.12

Lead author, Last author, Corresponding author,  ISSN  23752548

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Circadian gene expression driven by transcription activators CLOCK and BMAL1 is intimately associated with dynamic chromatin remodeling. However, how cellular metabolism directs circadian chromatin remodeling is virtually unexplored. We report that the S-adenosylhomocysteine (SAH) hydrolyzing enzyme adenosylhomocysteinase (AHCY) cyclically associates to CLOCK-BMAL1 at chromatin sites and promotes circadian transcriptional activity. SAH is a potent feedback inhibitor of S-adenosylmethionine (SAM)-dependent methyltransferases, and timely hydrolysis of SAH by AHCY is critical to sustain methylation reactions. We show that AHCY is essential for cyclic H3K4 trimethylation, genome-wide recruitment of BMAL1 to chromatin, and subsequent circadian transcription. Depletion or targeted pharmacological inhibition of AHCY in mammalian cells markedly decreases the amplitude of circadian gene expression. In mice, pharmacological inhibition of AHCY in the hypothalamus alters circadian locomotor activity and rhythmic transcription within the suprachiasmatic nucleus. These results reveal a previously unappreciated connection between cellular metabolism, chromatin dynamics, and circadian regulation.

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BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.

Welz PS, Zinna VM, Symeonidi A, Koronowski KB, Kinouchi K, Smith JG, Guillén IM, Castellanos A, Furrow S, Aragón F, Crainiciuc G, Prats N, Caballero JM, Hidalgo A, Sassone-Corsi P, Benitah SA

Cell 178 ( 4 ) 1029 2019.08

Lead author, Last author, Corresponding author,  ISSN  0092-8674

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BMAL1-Driven Tissue Clocks Respond Independently to Light to Maintain Homeostasis.

Welz PS, Zinna VM, Symeonidi A, Koronowski KB, Kinouchi K, Smith JG, Guillén IM, Castellanos A, Furrow S, Aragón F, Crainiciuc G, Prats N, Benitah SA

Cell  2019.08

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