Carotenoid Uptake and Protection in Cultured RPE - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 315

well as scavenger receptors: cluster determinant 36 (CD36), scavenger receptor class B type I (SR-BI)
and type II (SR-BII) (Calvo et al., 1997, 1998; Duncan et al., 2002; Provost et al., 2003; Ryeom
et al., 1996b). CD36, an 88 kDa integral membrane glycoprotein, preferentially binds oxidized LDL,
but also native HDL, LDL, and VLDL, which are subsequently endocytosed and degraded in cells
to release lipids (Calvo et al., 1998). In RPE cells, CD36 also participates in phagocytosis of shed
parts of POS (Ryeom et al., 1996a,b).
SR-BI, a 82 kDa glycoprotein with two cytoplasmic C- and N-terminal domains separated by a
large extracellular domain, acts mainly as a multiligand HDL receptor (Acton et al., 1996). In par-
ticular, SR-BI acts as receptor for anionic lipids and mediates selective uptake of HDL cholesteryl
esters and other lipids, vitamin E, and carotenoids, as well as transport from cells of free cholesterol
to lipoprotein and non-lipoprotein acceptors (Ji et al., 1997; Krieger, 1999; 2001; Reboul et al., 2005,
2006; Uittenbogaard et al., 2002). The major role of SR-BI in carotenoid uptake has been demon-
strated by comparison of b-carotene uptake in wild-type and SR-BI knockout mice and in vitro in a
polarized monolayer of the Caco-2 intestinal cell line, used as a model of human intestinal epithe-
lium (During and Harrison, 2007; Reboul et al., 2005, 2006). The polarized Caco-2 cells express
SR-BI mainly on their apical site. The incubation of these cells with SR-BI blocking antibodies or
other specii c inhibitors of SR-BI reduces the uptake of lutein solubilized in micelles by about 80%
and partly inhibits the lutein efl ux from cells into the basal side (Reboul et al., 2005). Interestingly,
lutein absorption from a micellar suspension of 900 nM lutein is reduced by 28% in the presence of
200 nM b-carotene but is not affected in the presence of 130 nM lycopene (Reboul et al., 2005). It
needs to be stressed, however, that in the experiments described, due to the solubility limitations, the
lycopene was tested at lower concentrations than b-carotene. Nevertheless, these data indicate that
there is a competition at least between some carotenoids for their uptake to cultured intestinal cells.
Recent data indicate that SR-BI is a nonspecii c receptor for many lipophilic molecules (Lorenzi
et al., 2008; Reboul et al., 2007b). Apart from HDLs, rodent SR-BI also binds to LDL, VLDL,
acetylated LDL, oxidized LDL, and maleylated bovine serum albumin. SR-BII has a similar ligand
specii city and function to that of SR-BI (Webb et al., 1998). However, it has been shown that
vitamin E (which like carotenoids is carried in the bloodstream mainly by LDL and HDL) is trans-
ported more efi ciently into the endothelial cells from HDLs than from LDLs (Balazs et al., 2004;
Kaempf-Rotzoll et al., 2003; Mardones and Rigotti, 2004). This is in striking contrast to choles-
terol, which is taken up much more efi ciently from LDLs than HDLs by the RPE to the retina
(Tserentsoodol et al., 2006b). It remains to be shown which lipoproteins are the main carriers for
carotenoids transported from blood into the RPE.
There are several factors which may be responsible for the variability in the uptake of different
carotenoids. These include differences in the distribution of carotenoids among serum lipoproteins
and differences in the expression on cell membranes of the various receptors/transporters respon-
sible for uptake of different types of lipoproteins. It may be further expected that the efi ciencies
for uptake of different carotenoids may vary for different types of receptors/transporters. Also, the
further processing of internalized different carotenoids may vary.
The roles of lipoprotein and scavenger receptors, particularly SR-BI/II and CD36, in carotenoid
uptake in the RPE cells still awaits exhaustive investigation.
15.3.2.2 Metabolic Pathways in the RPE of Pro-Vitamin A Carotenoids
b-carotene does not accumulate in the neural retina in detectable amounts—its concentration in
the neural retina is at most 1% of total carotenoid content (Handelman et al., 1991a). However, it
is present in substantial concentrations in the combined RPE-choroid tissues isolated from human
cadaver eyes (Bernstein et al., 2001). RPE highly expresses the BCO enzyme and actively converts
b-carotene into all- trans -retinal (Bhatti et al., 2003; Chichili et al., 2005). BCO has been also
detected in bovine neural retina (Chichili et al., 2005). Thus it may be suspected that conversion
to vitamin A is the typical fate of b-carotene in the retina. Vitamin A is important for vision as a
precursor of the visual pigment chromophore, 11- cis -retinal (Figure 15.2a).