title: Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice.
abstract: Riboflavin (vitamin B2) acts as an intermediary during various biochemical oxidation-reduction reactions in the liver. Hepatic riboflavin homeostasis is suggested to be maintained through its transporter(s). Riboflavin transporters, RFVT2/Slc52a2 and RFVT3/Slc52a3, have been identified in rodents. However, the role of each RFVT in the hepatic homeostasis of riboflavin has not yet been fully clarified. In this study, we assessed the contribution of each RFVT to riboflavin uptake into the liver using in vitro and in vivo studies. The uptake of riboflavin by mouse primary hepatocytes increased in a time-dependent and a concentration-dependent manner. Riboflavin transport was independent of extracellular Na(+). However, the uptake decreased slightly along with the extracellular pH increases. Real-time PCR analysis revealed that the mRNA level of Slc52a2, or coding for mouse (m)RFVT2, in the mouse liver was 10 times higher than that of Slc52a3 (coding for mRFVT3). The uptake of riboflavin at pH 7.4 by primary hepatocytes was significantly decreased by the transfection of Slc52a2-small interfering RNA (siRNA), but not Slc52a3-siRNA. Furthermore, we also confirmed the contribution of riboflavin transporters in vivo. The riboflavin concentrations in plasma, but not in the liver, were significantly decreased in mice fed on a riboflavin-deficient diet for 8 weeks. The expression of Slc52a2 mRNA was significantly upregulated by riboflavin deprivation. These results strongly suggest that mRFVT2 was involved in hepatic riboflavin homeostasis.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yonezawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshimatsu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Omura
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D001692:Biological Transport; D022781:Hepatocytes / Q000378:metabolism; D006706:Homeostasis; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012256:Riboflavin / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; C588176:RFVT2 protein, mouse; D012256:Riboflavin
keywords: Carrier-mediated transport; Hepatic homeostasis; Vitamin B2