1.

学位論文
学位
1. 有機カチオン膜輸送体による神経分化とミクログリア活性化の制御
石本, 尚大 ; Ishimoto, Takahiro
出版情報: 博士論文要旨Abstract. 
URL: http://hdl.handle.net/2297/00051377
概要: 博士論文要旨Abstract 以下に掲載：Neurochemical Research 43(1) pp.116-128 2018. Springer US. 共著者：Takahiro Ishimoto, Noritaka Nakamichi, Hikari Nishijima, Yusuke Masuo, Yukio Kato
2.

学位論文
学位
2. 有機カチオン膜輸送体による神経分化とミクログリア活性化の制御
石本, 尚大 ; Ishimoto, Takahiro
出版情報: 博士論文本文Full. 
URL: http://hdl.handle.net/2297/00051388
概要: 博士論文本文Full 以下に掲載：Neurochemical Research 43(1) pp.116-128 2018. Springer US. 共著者：Takahiro Ishimoto, Noritaka Nakamichi, Hikari Nishijima, Yusuke Masuo, Yukio Kato
3.

論文
論文
3. Gene Ablation of Carnitine/Organic Cation Transporter 1 Reduces Gastrointestinal Absorption of 5-Aminosalicylate in Mice
Shimizu, Takuya ; Kijima, Ai ; Masuo, Yusuke ; Ishimoto, Takahiro ; Sugiura, Tomoko ; Takahashi, Saki ; Nakamichi, Noritaka ; Kato, Yukio
出版情報: Biological and Pharmaceutical Bulletin.  38  pp.774-780,  2015-05-01.  Pharmaceutical Society of Japan = 日本薬学会
URL: http://hdl.handle.net/2297/43035
概要: 5-Aminosalicylic acid (5-ASA) is an orally administered therapeutic agent for inflammatory bowel diseases, such as ulcer … ative colitis and Crohn’s disease. We hypothesized that the absorption of 5-ASA is mediated by the polyspecific carnitine/organic cation transporter (OCTN1/SLC22A4), based on the similarity of chemical structure between 5-ASA and other OCTN1 substrates. Therefore, we examined the involvement of this transporter in the disposition of 5-ASA in vivo by using octn1 gene knockout (octn1−/−) mice. After oral administration of 5-ASA, the plasma concentrations of 5-ASA and its primary metabolite, N-acetyl-5-aminosalicylate (Ac-5-ASA), in octn1−/− mice were much lower than those in wild-type mice. The time required to reach maximum plasma concentration was also delayed in octn1−/− mice. On the other hand, the plasma concentration profiles of both 5-ASA and Ac-5-ASA after intravenous administration of 5-ASA (bolus or infusion) were similar in the two strains. Uptake of 5-ASA from the apical to the basal side of isolated small-intestinal tissues of octn1−/− mice, determined in an Ussing-type chamber, was lower than that in wild-type mice. Further, uptake of 5-ASA in HEK293 cells stably transfected with the OCTN1 gene, assessed as the sum of cell-associated 5-ASA and Ac-5-ASA, was higher than that in HEK293 cells transfected with the vector alone. Overall, these results indicate that OCTN1 is involved, at least in part, in the gastrointestinal absorption of 5-ASA. 続きを見る
4.

論文
論文
4. Gene Ablation of Carnitine/Organic Cation Transporter 1 Reduces Gastrointestinal Absorption of 5-Aminosalicylate in Mice
Shimizu, Takuya ; Kijima, Ai ; Masuo, Yusuke ; Ishimoto, Takahiro ; Sugiura, Tomoko ; Takahashi, Saki ; Nakamichi, Noritaka ; Kato, Yukio
出版情報: Biological and Pharmaceutical Bulletin.  38  pp.774-780,  2015-01-01.  日本薬学会 = The Pharmaceutical Society of Japan
URL: http://hdl.handle.net/2297/43897
概要: 5-Aminosalicylic acid (5-ASA) is an orally administered therapeutic agent for inflammatory bowel diseases, such as ulcer … ative colitis and Crohn’s disease. We hypothesized that the absorption of 5-ASA is mediated by the polyspecific carnitine/organic cation transporter (OCTN1/SLC22A4), based on the similarity of chemical structure between 5-ASA and other OCTN1 substrates. Therefore, we examined the involvement of this transporter in the disposition of 5-ASA in vivo by using octn1 gene knockout (octn1−/−) mice. After oral administration of 5-ASA, the plasma concentrations of 5-ASA and its primary metabolite, N-acetyl-5-aminosalicylate (Ac-5-ASA), in octn1−/− mice were much lower than those in wild-type mice. The time required to reach maximum plasma concentration was also delayed in octn1−/− mice. On the other hand, the plasma concentration profiles of both 5-ASA and Ac-5-ASA after intravenous administration of 5-ASA (bolus or infusion) were similar in the two strains. Uptake of 5-ASA from the apical to the basal side of isolated small-intestinal tissues of octn1−/− mice, determined in an Ussing-type chamber, was lower than that in wild-type mice. Further, uptake of 5-ASA in HEK293 cells stably transfected with the OCTN1 gene, assessed as the sum of cell-associated 5-ASA and Ac-5-ASA, was higher than that in HEK293 cells transfected with the vector alone. Overall, these results indicate that OCTN1 is involved, at least in part, in the gastrointestinal absorption of 5-ASA. 続きを見る
5.

論文
論文
5. 記憶学習のメカニズム解析及び血漿中脳由来エクソソームを利用した記憶学習能力の評価
石本, 尚大 ; Ishimoto, Takahiro
出版情報: 令和2(2020)年度 科学研究費補助金 基盤研究(C) 研究成果報告書 = 2020 Fiscal Year Final Research Report.  2019-08-30 – 2021-03-31  pp.8p.-,  2021-04-21. 
URL: http://hdl.handle.net/2297/00058930
概要: 金沢大学医薬保健研究域薬学系<br />ヒトの認知機能を改善させるergothioneine (ERGO)を経口投与したマウス及び対照群の記憶を司る海馬歯状回(DG)においてプロテオミクス解析を行い、発現が増加したある候補蛋白質に着目し、そ … の発現を抑制するアデノ随伴ウイルス(AAV)を構築し、マウスDG特異的にこのAAVを感染させると神経突起の伸長が抑制された。健常人と軽度認知障害患者をERGO投与群と偽薬投与群に分け、血清中エクソソーム画分を比較すると、ある候補蛋白質の発現量がERGO投与群で有意に高く、その発現量と血清中ERGO濃度および一部の認知機能検査の評価項目と正の相関を示した。<br />Ergothioneine (ERGO) is known to enhance cognitive function in human. Proteome analysis in mice showed oral administration of ERGO remarkably increased several proteins in hippocampal dentate gyrus (DG). Knockdown of a candidate protein in murine hippocampal DG by adeno-associated virus significantly enhanced neurite outgrowth, which may be one of the mechanisms underlying cognitive enhancement by ERGO.Protein expression profile on exosomes derived from the brain in plasma may reflect the ERGO-induced enhancement of cognitive function. Expression of a candidate protein on exosomes in serum was associated with ERGO exposure and cognitive function, which might be a possible biomarker for assessment of ERGO-induced beneficial activity in the human brain.<br />研究課題/領域番号:19K23797, 研究期間(年度):2019-08-30 – 2021-03-31<br />出典：「記憶学習のメカニズム解析及び血漿中脳由来エクソソームを利用した記憶学習能力の評価」研究成果報告書　課題番号19K23797（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-19K23797/19K23797seika/）を加工して作成 続きを見る