title: Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter.
abstract: OBJECTIVE
  Ingestion of flavonoid-rich beverages acutely affects endothelial function, causing vasodilation. This effect might be dependent on flavonoid transport into the endothelium. We investigated flavonoid uptake into vascular endothelial cells and whether this was mediated by bilitranslocase (TC 2.A.65.1.1), a bilirubin-specific membrane carrier that also transports various dietary flavonoids.
  
  
  RESULTS
  Human and rat aortic primary endothelial cells as well as Ea.hy 926 cells were found to express bilitranslocase, as assessed by immunocytochemistry and immunoblotting analysis using anti-sequence bilitranslocase antibodies targeting two distinct extracellular epitopes of the carrier. Bilitranslocase function was tested by measuring the rate of bromosulfophthalein (a standard bilitranslocase transport substrate) uptake into endothelial cells and was inhibited not only by bilitranslocase antibodies but also by quercetin (a flavonol). Similarly, uptake of both quercetin and malvidin 3-glucoside (an anthocyanin) were also found to be antibody-inhibited. Quercetin uptake into cells was inhibited by bilirubin, suggesting flavonoid uptake via a membrane pathway shared with bilirubin.
  
  
  CONCLUSIONS
  The uptake of some flavonoids into the vascular endothelium occurs via the bilirubin-specific membrane transporter bilitranslocase. This offers new insights into the vascular effects of both flavonoids and bilirubin.
authors.affiliation: Dipartimento di Scienze della Vita, Università di Trieste, via L. Giorgieri 1, 34127 Trieste, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maestro
authors.forename: Michela
authors.initials: M
authors.lastname: Terdoslavich
authors.forename: Andreja
authors.initials: A
authors.lastname: Vanzo
authors.forename: Adenike
authors.initials: A
authors.lastname: Kuku
authors.forename: Federica
authors.initials: F
authors.lastname: Tramer
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nicolin
authors.forename: Fulvio
authors.initials: F
authors.lastname: Micali
authors.forename: Giuliana
authors.initials: G
authors.lastname: Decorti
authors.forename: Sabina
authors.initials: S
authors.lastname: Passamonti
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism; D001692:Biological Transport; D002460:Cell Line; D002570:Ceruloplasmin; D004730:Endothelium, Vascular / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D005960:Glucosides; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000502:physiology*; D011794:Quercetin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013448:Sulfobromophthalein / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D005419:Flavonoids; D005960:Glucosides; D008565:Membrane Proteins; D013448:Sulfobromophthalein; C458419:malvidin-3-glucoside; D011794:Quercetin; D002570:Ceruloplasmin; C033838:bilitranslocase; D001663:Bilirubin