Xanthophylls are preferentially taken up compared with β-carotene by retinal cells via a SRBI-dependent mechanism*

Abstract

The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. bcarotene (b-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7-9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than b-C (P , 0.05). At 9 weeks, cellular uptakes were 1.6, 2.5, and 3.2%, respectively, for b-C, LUT, and ZEA. Similar extents were observed when carotenoids were delivered in either Tween 40 or "chylomicrons" produced by Caco-2 cells. Differentiated ARPE-19 cells did not exhibit any detectable b-C 15,15′-oxygenase activity or convert exogenous b-C into vitamin A. When using specific antibodies against the lipid transporters cluster determinant 36 (CD36) and scavenger receptor class B type I (SR-BI), cellular uptake of b-C and ZEA were significantly decreased (40-60%) with anti-SR-BI but not with anti-CD36. Small interfering RNA transfection for SR-BI led to marked knockdown of SR-BI protein expression (?90%), which resulted in decreased b-C and ZEA uptakes by 51% and 87%, respectively. Thus, the present data show that RPE cells preferentially take up xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for b-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina.-During, A., S. Doraiswamy, and E. H. Harrison. Xanthophylls are preferentially taken up compared with b-carotene by retinal cells via a SRBI-dependent mechanism.

A CD36-related Transmembrane Protein Is Coordinated with an Intracellular Lipid-binding Protein in Selective Carotenoid Transport for Cocoon Coloration

“…SR-BI was proposed to form a hydrophobic channel along which cholesteryl esters migrate (37). Furthermore, mutants of the ninaD gene, a homolog of SR-BI in the fruit fly Drosophila melanogaster, was reported to affect carotenoid uptake in gut for visual chromophore synthesis (38 -40), and SR-BI was also implicated in cellular carotenoid absorption (41)(42)(43)(44). Therefore, we considered these two genes to be strong candidates for the C gene, and designated the gene nearer the SNP marker C-080419-R16 Cameo1 and the other Cameo2.…”

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

“…RPE expresses functional receptors for both LDL (LDL-R) and HDL (scavenger receptor B-I, SRB-I) and takes up these plasma lipoproteins ( 109,(135)(136)(137)(138), likely for resupply of essential lipophilic nutrients and cellular constituents. LDL-derived cholesterol taken up by RPE partitions remarkably fast (within hours) into membranes of the neurosensory retina ( 109,139 ).…”

Mechanisms of selective delivery of xanthophylls to retinal pigment epithelial cells by human lipoproteins

“…Previous work in our laboratory (28,29) demonstrated that xanthophylls associated mostly with HDL, while -cryptoxanthin, lycopene, and -carotene predominantly associated with LDL in human serum. We also showed that zeaxanthin delivered by detergent micelles to ARPE-19 cells is preferentially taken up via an SR-B1-dependent mechanism compared with -carotene (23). The current work was designed to extend those studies and to investigate in detail the uptake and metabolism of lutein, zeaxanthin, meso-zeaxanthin, and -carotene delivered in their physiologically relevant transport vehicles.…”

“…Differentiated ARPE-19 cells are often used as a model for the study of retinal metabolism because they show structural and functional properties similar to the human RPE (20). ARPE-19 cells express lipoprotein receptors necessary for studying lipoprotein delivery of carotenoids, including scavenger receptor class B1 (SR-B1), SR-B2, LDL receptor (LDLR), lipid transporters cluster determinant 36 (CD-36), and ABCA1 (21)(22)(23)(24)(25)(26)(27). Based on analysis of the expression of lipoprotein transporters and receptors in the retina and two different RPE cell lines, including ARPE-19 cells, it was proposed that circulating LDL and HDL enter the basolateral side of the RPE via the LDLR and SR-B1 (27).…”