Expression of bilitranslocase in the vascular endothelium and its function as a flavonoid transporter.
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.
Maestro
Alessandra
A
Dipartimento di Scienze della Vita, Università di Trieste, via L. Giorgieri 1, 34127 Trieste, Italy.
Terdoslavich
Michela
M
Vanzo
Andreja
A
Kuku
Adenike
A
Tramer
Federica
F
Nicolin
Vanessa
V
Micali
Fulvio
F
Decorti
Giuliana
G
Passamonti
Sabina
S
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
D000872:Anthocyanins; D005419:Flavonoids; D005960:Glucosides; D008565:Membrane Proteins; D013448:Sulfobromophthalein; C458419:malvidin-3-glucoside; D011794:Quercetin; D002570:Ceruloplasmin; C033838:bilitranslocase; D001663:Bilirubin