title: Functional characterization of ergothioneine transport by rat organic cation/carnitine transporter Octn1 (slc22a4).
abstract: It has been reported that organic cation/carnitine transporter 1 (OCTN1) is associated with rheumatoid arthritis and Crohn's disease. Additionally, we reported that OCTN1 is expressed in hematopoietic cells, and is associated with proliferation and differentiation of erythroid cells. However, physiological role of OCTN1 is still unclear. Ergothioneine, an anti-oxidant, was recently reported to be a good substrate of human OCTN1. However, the transport characteristics of ergothioneine in rat remains to be clarified. The present study, is to further investigate the role of rat Octn1 on transport of ergothioneine in rat Octn1 transfected cells and natively expressing cell line PC12 derived from rat adrenal pheochromocytoma. [(3)H]Ergothioneine uptake by rat Octn1 stably transfected HEK293 cells was saturable, sodium dependent with 1 : 1 stoichiometry of ergothioneine, and pH dependent. Since ergothioneine was reported to presumably play a protective role against oxidative stress-induced apoptosis in PC12 cells, its transport in this cell line was investigated. The expression of rat Octn1 and a saturable and Na(+)-dependent transport of ergothioneine were observed in PC12 cells, suggesting that ergothioneine transport in this cell line may be mediated by rat Octn1. These findings suggested that rat Octn1 may act as a survival factor by taking up ergothioneine to suppress oxidative stress in this cell line. In conclusion, functional characteristics of ergothioneine transport by rat Octn1 is similar to that of human OCTN1 and it is suggested that rat Octn1 is important by transporting anti-oxidant ergothioneine in PC12 cells, though its role in vivo is to be investigated.
authors.affiliation: Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hikaru
authors.initials: H
authors.lastname: Yabuuchi
authors.forename: Tomoji
authors.initials: T
authors.lastname: Maeda
authors.forename: Ikumi
authors.initials: I
authors.lastname: Tamai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism*; D004880:Ergothioneine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D027701:Organic Cation Transport Proteins; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D000070590:Solute Carrier Proteins; D027981:Symporters; D014162:Transfection
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D008565:Membrane Proteins; D027701:Organic Cation Transport Proteins; C000705567:Slc22a4 protein, rat; D000070590:Solute Carrier Proteins; D027981:Symporters; D012964:Sodium; D004880:Ergothioneine