Carotenoid Uptake and Protection in Cultured RPE - Carotenoids: Physical, Chemical, and Biological Functions and Properties - page 319

associated. The best-known enzymatic function of many GSTs is conjugation of glutathione to
various nonpolar electrophilic metabolites, such as epoxides or unsaturated aldehydic products of
lipid peroxidation (Ellis, 2007). However, GSTs may exhibit other functions, including peroxidase
activity and isomerase activity toward various unsaturated compounds.
GSTP1 is one of cytosolic enzymes. Interestingly, Bernstein et al. have demonstrated that the
human recombinant isoforms, GSTM1 and GSTA1, which are also cytosolic enzymes, exhibit very
low afi nity binding for zeaxanthin in comparison to GSTP1 (Bhosale et al., 2004). Other potential
XBPs, namely, tubulin, albumin, HDL, LDL, and b-lactoglobulin, have not exhibited high-afi nity
saturable binding of zeaxanthin comparable with that of GSTP1.
Interestingly, none of those three isoforms of GSTs tested has exhibited high-afi nity binding
of lutein. Out of all other candidate proteins tested, only albumin has exhibited saturable high-
afi nity binding for lutein (Bhosale et al., 2004). It may be suggested that XBPs may be involved
in specii c accumulation of xanthophylls as well as in xanthopyll transport inside the cells or even
in between cells.
It needs to be noted that apart from expression of lipoprotein receptors, RPE itself expresses
several apolipoproteins (Bartl et al., 2001; Ishida et al., 2004; Li et al., 2006; Malek et al., 2003;
Tserentsoodol et al., 2006a). So far, six apolipoproteins have been identii ed as being expressed
by the RPE, namely, apolipoprotein A-I (ApoA-I), ApoB, ApoC-I, ApoC-II, ApoE, and ApoJ
(clusterin) (Bailey et al., 2004; Bartl et al., 2001; Ishida et al., 2004; Li et al., 2006; Malek et al.,
2003; Tserentsoodol et al., 2006a). In addition to their functions as lipid transporters and receptor
ligands, apo-lipoproteins can act as modulators of several enzymes. The basic characteristics of
apo-lipoproteins expressed by the RPE are described below.
ApoA-I is the major apo-lipoprotein of HDL (Tserentsoodol et al., 2006a; Zannis et al., 2006),
which is involved in lipid efl ux from peripheral cells and its transport to the liver. Also, free ApoA-I
has been shown to act as an acceptor for cholesterol secreted from cells and to stimulate its efl ux.
ApoB is a component of chylomicrons and VLDL and is essential in liver, intestine, and heart for
assembly of large lipoproteins containing triglyceride and esterii ed cholesterol (Bjorkegren et al.,
2001). To assemble lipoproteins containing ApoB, a microsomal triglyceride transfer protein (MTP)
is required (Li et al., 2005). Signii cantly, Curcio and colleagues have demonstrated that human
RPE and neural retina synthesizes MTP, and the RPE assembles and secretes ApoB-containing
lipoproteins in vitro (Li et al., 2005; Malek et al., 2003). They have suggested that these lipoproteins
secreted by the RPE may then accumulate on the basal side of the RPE as age-related deposits in
Bruch's membrane (Li et al., 2005; Malek et al., 2003).
ApoC-I is expressed mainly in liver but also in lung, skin, testis, spleen, neural retina, and RPE.
Its multiple functions include the activation of lecithin cholesterol acyltransferase (LCAT) and the
inhibition, among others, of lipoprotein and hepatic lipases that hydrolyze triglycerides in particle
cores. Notably, both LCAT and lipoprotein lipases are expressed in RPE and choroid (Li et al.,
2006). Moreover ApoC-I has been shown to displace ApoE on the VLDL and LDL and thus hinder
their binding and uptake via their corresponding receptors (Li et al., 2006).
ApoC-II is expressed in liver and intestine, and both the neural retina and RPE (Li et al., 2006).
In contrast to ApoC-I, it can function as an activator of lipoprotein lipase. Similar to ApoA-I,
ApoA-II, and ApoE, in the absence of lipid to stabilize its structure, ApoC-II forms amyloid
assemblies.
ApoE is a component of VLDL, HDL, and chylomicrons and is expressed in many tissues includ-
ing the RPE and neural retina. It is found in atherosclerotic intima and sub-RPE deposits (Anderson
et al., 2001; Malek et al., 2003). Interestingly, free ApoE is a ligand for the SR-BI receptor and
stimulates selective uptake of cholesterol esters from HDLs (Bultel-Brienne et al., 2002). ApoE
has anti-angiogenic, anti-inl ammatory, and antioxidant effects (Browning et al., 1994; Kelly et
al., 1994; Tangirala et al., 2001). Its importance in the retina is highlighted by the fact that certain
isoforms of ApoE, ApoE-2, and ApoE-4 are associated with an increased and decreased risk of
AMD, respectively (Thakkinstian et al., 2006). In human eyes, post mortem ApoE has been found