Gene Knockout and Metabolome Analysis of Carnitine/Organic Cation Transporter OCTN1
Open accessAbstract
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 [(3)H]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.
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ERG is metabolised and excreted only slowly.
“ERG is metabolised and excreted only slowly(360,371,401,402).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [401]
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- Authors
- Kato, Y., Kubo, Y., Iwata, D., Kato, S., Sudo, T., Sugiura, T., Kagaya, T., Wakayama, T., Hirayama, A., Sugimoto, M., Sugihara, K., Kaneko, S., Soga, T., Asano, M., Tomita, M., Matsui, T., Wada, M., & Tsuji, A.
- Affiliations
- Kanazawa University (JP)
- Kanazawa University Hospital (JP)
- Institute for Advanced Biosciences, Keio University (JP)
- Fukuoka University (JP)
- Nagasaki International University (JP)
- Corresponding author
- Tsuji, Akira
- ORCID
- Venue
- Pharmaceutical Research
- Published
- 2010-03-12
- Volume
- 27
- Issue
- 5
- Pages
- 832-840
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W1988144958
- Cited by
- 206
- References
- 31
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 20 · 2023: 11 · 2022: 14 · 2021: 17 · 2020: 15 · 2019: 9 · 2018: 11 · 2017: 13 · 2016: 12 · 2015: 14 · 2014: 11 · 2013: 11 · 2012: 10
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Kanazawa University Repository for Academic Resources (DSpace) (Kanazawa University) (submittedVersion, cc-by-nc-nd)
- Funders
- Kanazawa University
- Japan Society for the Promotion of Science (22790152)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- OCTN1, SLC22A4, knockout mice, ergothioneine, pharmacokinetics, intestinal inflammation, ischemia-reperfusion injury, Crohn's disease, ulcerative colitis, inflammatory bowel disease, antioxidants, tubular reabsorption
- MeSH terms
- Adolescent, Adult, Aged, Animals, Antioxidants, Carrier Proteins, Chromatography, High Pressure Liquid, Crohn Disease, Ergothioneine, Female, Genotype, Humans, Intestinal Absorption, Intestines, Ischemia, Japan, Male, Membrane Proteins, Microvilli, Middle Aged, Spectrophotometry, Ultraviolet, Blotting, Southern, Blotting, Western, Reperfusion Injury, Mice, Knockout, Oxidative Stress, Organic Cation Transport Proteins, Symporters, Mice, Metabolomics, Young Adult
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