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Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1.
Pharm Res. 2010 May; 27(5):832-40.PR

Abstract

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.

Authors+Show Affiliations

Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, 920-1192, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20224991

Citation

Kato, Yukio, et al. "Gene Knockout and Metabolome Analysis of Carnitine/organic Cation Transporter OCTN1." Pharmaceutical Research, vol. 27, no. 5, 2010, pp. 832-40.
Kato Y, Kubo Y, Iwata D, et al. Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res. 2010;27(5):832-40.
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. (2010). Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharmaceutical Research, 27(5), 832-40. https://doi.org/10.1007/s11095-010-0076-z
Kato Y, et al. Gene Knockout and Metabolome Analysis of Carnitine/organic Cation Transporter OCTN1. Pharm Res. 2010;27(5):832-40. PubMed PMID: 20224991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. AU - Kato,Yukio, AU - Kubo,Yoshiyuki, AU - Iwata,Daisuke, AU - Kato,Sayaka, AU - Sudo,Tomohisa, AU - Sugiura,Tomoko, AU - Kagaya,Takashi, AU - Wakayama,Tomohiko, AU - Hirayama,Akiyoshi, AU - Sugimoto,Masahiro, AU - Sugihara,Kazushi, AU - Kaneko,Shuichi, AU - Soga,Tomoyoshi, AU - Asano,Masahide, AU - Tomita,Masaru, AU - Matsui,Toshiyuki, AU - Wada,Morimasa, AU - Tsuji,Akira, Y1 - 2010/03/12/ PY - 2009/11/02/received PY - 2010/02/01/accepted PY - 2010/3/13/entrez PY - 2010/3/13/pubmed PY - 2010/7/14/medline SP - 832 EP - 40 JF - Pharmaceutical research JO - Pharm Res VL - 27 IS - 5 N2 - 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. SN - 1573-904X UR - https://www.unboundmedicine.com/medline/citation/20224991/Gene_knockout_and_metabolome_analysis_of_carnitine/organic_cation_transporter_OCTN1_ L2 - https://doi.org/10.1007/s11095-010-0076-z DB - PRIME DP - Unbound Medicine ER -