1 – Understanding the structure and the function of Bilitranslocase
Bilirubin membrane transport
Bilitranslcase (TC #2.A.65.1.1) is a polypeptide derived by a truncated cDNA isolated from rat liver in 1998 (Biochem Biophys Res Comm 1998). By means of anti-sequence antibodies, this polypeptide has been related to the membrane transporter of bilirubin in human liver cells (FEBS J. 2005) and in the human vascular endothelium (Cardiovasc Res. 2010; Free Radical Biol. Med. 2012; Nutr Metab Cardiovasc Dis. 2013). It is as a distinct entity from other organic anion transporters, e.g. OATP (Drug Metabolism Letters 2012).
The transporter has two main conformational states, regulated by oxidation of cysteines (FEBS Journal 1998). Thus, it is sensitive to the cellular redox balance.
Substrate specificity: flavonoids and nucleotides
A specific transport assay is plasma membrane vesicles, called electrogenic BSP transport assay (Methods Mol Biol. 2010), enables substrate screening. Bilitranslocase has been found to interact with most dietary anthocyanins (a flavonoid sub-class) (Biochem Biophys Res Comm 2002, Biochem Pharmacol 2007) and nucleotides, but neither nucleosides nor nucleo bases (Anal Chim Acta 2011).
2 – Understanding the mechanisms of flavonoid bioavailability (from the gut to our tissues)
Gastric absorption of anthocyanins, and their rapid tissue distribution to the excretory organs and the brain (FEBS Letters 2002, J Agric Food Chem 2005, Mol Nutr Food Res 2008, J Nat Prod. 2011). Unique pharmacokinetics-unique intervention strategies.
Flavonoids induce vasodilation and cardioprotection in the cardiovascular system, by a bilitranslocase-mediated membrane transport (Free Rad Biol Med 2013,Nutr Metab Cardiovasc Dis. 2013, Food&Function 2013).
3 – Finding Bilitranslocase homologues in plants
By means of anti-sequence antibodies, homologues have been found in carnation petals (FEBS J. 2005), grape (Planta. 2008, J Exp Bot. 2009, Methods Mol Biol. 2010) and pea (J Bioenerg Biomembr. 2014).