Carotenoid transport

Caco-2 cells and ezetimibe, a potent inhibitor of chloresterol absorption in humans, it was reported that (1) carotenoid transport was inhibited by ezetimibe up to 50% and the extent of that inhibition diminished with increasing polarity of the carotenoid molecule, (2) the inhibitory effects of ezetimibe and the antibody against SR-BI on P-carotene transport were additive, and (3) ezetimibe may interact physically with cholesterol transporters as previously suggested - and also down-regulate the gene expression of three surface receptors, SR-BI, NPCILI, and ABCAl. 

The hypothesis of the participation of those cholesterol transporters (NPCILI and ABCAl) in the carotenoid transport remains to be confirmed, especially at the in vivo human scale. If the mechanism by which carotenoids are transported through the intestinal epithelial membrane seems better understood, the mechanism of intracellular carotenoid transport is yet to be elucidated. The fatty acid binding protein (FABP) responsible for the intracellular transport of fatty acids was proposed earlier as a potential transporter for carotenoids. FABP would transport carotenoids from the epithelial cell membrane to the intracellular organelles such as the Golgi apparatus where CMs are formed and assembled, but no data have illustrated this hypothesis yet. 

During, A., Dawson, H.D., and Harrison, E.H., Carotenoid transport is decreased and expression of the lipid transporters SR-Bl, NPCILI, and ABCAl is down-regulated in Caco-2 cells treated with ezetimibe, J. Nutr., 135, 2305, 2005. 

Recent data indicate that SR-BI is a nonspecific 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 specificity 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 transported more efficiently 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 cholesterol, which is taken up much more efficiently 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. 

Once internalized within the RPE, there must be a mechanism for carotenoid transport to photoreceptors. The RPE metabolizes lipids from phagocytosed POS and provides a constant supply of lipids to photoreceptors for the synthesis of new discs and molecular renewal of lipids within existing discs (Strauss, 2005). Thus there is a constant transfer of lipids from the RPE to photoreceptors. It has been shown in the rabbit and monkey that intraveneous administration of lipophilic benzopor-phyrin bound to LDLs results in an efficient delivery of the fluorescent photosensitizer not only to the RPE but also to photoreceptors this occurs within 20 min following injection (Haimovici et al., 1997 Miller et al., 1995). 

While it may be speculated that in the RPE both lipoprotein and/or scavenger receptors are likely to be involved in carotenoid uptake from the blood, it is not clear what mechanism(s) are responsible for carotenoid transport through the RPE into the neural retina. Also, it is not clear what mechanism(s) are responsible for selective accumulation in the retina of only two carotenoids. 

In addition to its presence in the RPE, ABCA1 has been found to be localized in the neural retina, particularly in the ganglion cell layer and rod photoreceptor inner segments (Tserentsoodol et al., 2006a), suggesting it may be involved in carotenoid transport throughout the retina. 

Altogether, there are many unknowns about carotenoid transport in the retina. However, present knowledge on carotenoid uptake in other cell types and the finding of multiple proteins potentially involved in carotenoid transport in the RPE and adjacent neural retina leads to the suggestion that several hypothetical pathways exist (Figure 15.3). Many such pathways can be easily tested in cultured RPE. 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

Trams, E. G. 1969. Carotenoid transport in the plasma of the scarlet ibis (Eudocimus ruber). Comp. Biochem. Physiol. 28 1177-1184. 

Link between CBP and a Genetic Locus Responsible for Carotenoid Transport.515... 

Animals cannot synthesize carotenoids de novo. To deposit carotenoids in the proper tissues in the proper amounts, they must acquire carotenoids from dietary sources and transport them to target sites. Knowledge of the molecular mechanisms of carotenoid transport, however, is still... 

FIGURE 24.1 The pathway of carotenoid transport in the silkworm. Carotenoids are absorbed from dietary mulberry leaves into the intestinal mucosa, transferred to the hemolymph (1), transported in the hemolymph by plasma lipoproteins (2), and accumulated in the silk gland (3). 

LINK BETWEEN CBP AND A GENETIC LOCUS RESPONSIBLE FOR CAROTENOID TRANSPORT... 

FIGURE 24.4 Silkworm genetic loci responsible for carotenoid transport, (a) List of the genetic loci. + indicates a recessive allele of I. (b) Schematic illustration of the function of the F, I, and C genes. Only larvae with the genotype Y + C] transport carotenoids into the silk gland and create yellow cocoons. 

FIGURE 24.6 Model of the molecular function of CBP. CBP moves in the cytosol and relays carotenoid in combination with the lipophorin in the hemolymph. At the membrane, other factors might be involved in the carotenoid transport (magnification, see the text for explanation). 

The yellow coloration in the Monarch as well as the larva of three other species of butterfly from South Florida is exclusively due to the specific accumulation of exceptionally high levels of lutein producing a pigmented epidermis. This active accumulation, reminiscent of the specific accumulation that occurs in the primate macula, indicates that butterfly larva is an excellent animal model for the study of carotenoid transport and binding. As such, elucidation of the mechanism of transport and binding of lutein in the epidermis and other tissues of these butterfly larvae may provide insight into xanthophyll uptake within the human eye (Bhosale et al. 2004). 

The hydrophobicity of these compounds requires protein binding to move carotenoids through aqueous environments an emerging area of research includes the identification of carotenoid transport proteins that determine, in part, carotenoid tissue concentrations. As carotenoids are found throughout nature, various models can be studied for example, Chapter 24 describes carotenoid... 

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