Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1
スポンサーリンク
概要
- 論文の詳細を見る
Purpose: Solute carrier OCTN1 (SLC22A4) is an orphan transporter, the physiologically important substrate of which is still unidentified. The aim of the present study was to examine physiological roles of OCTN1. Methods: We first constructed octn1 gene knockout (octn1-/-) mice. Metabolome analysis was then performed to identify substrates in vivo. The possible association of the substrate identified with diseased conditions was further examined. Results: The metabolome analysis of blood and several organs indicated complete deficiency of a naturally occurring potent antioxidant ergothioneine in octn1-/- mice among 112 metabolites examined. Pharmacokinetic analyses after oral administration revealed the highest distribution to small intestines and extensive renal reabsorption of [3H]ergothioneine, both of which were much reduced in octn1-/- mice. The octn1-/- mice exhibited greater susceptibility to intestinal inflammation under the ischemia and reperfusion model. The blood ergothioneine concentration was also much reduced in Japanese patients with Crohn's disease, compared with healthy volunteers and patients with another inflammatory bowel disease, ulcerative colitis. Conclusions: These results indicate that OCTN1 plays a pivotal role for maintenance of systemic and intestinal exposure of ergothioneine, which could be important for protective effects against intestinal tissue injuries, providing a possible diagnostic tool to distinguish the inflammatory bowel diseases. © 2010 Springer Science+Business Media, LLC.
論文 | ランダム
- 講義シリーズ 量子力学と信号処理(18)一般化無損失波動方程式の共鳴および固有値問題
- 講義シリーズ 量子力学と信号処理(17)1次元無損失の一般化波動方程式および波動関数
- 講義シリーズ 量子力学と信号処理(16)ディラック方程式とそのディジタル信号処理への応用
- 講義シリーズ 量子力学と信号処理(15)回路理論の特徴をよく表す縦続行列
- 暴力考(5・完)人間学的視点から