Scavenger receptor class B type

FIGURE 3.2.2 Metabolic pathways of carotenoids such as p-carotene. CM = chylomicrons. VLDL = very low-density lipoproteins. LDL = low-density lipoproteins. HDL = high-density lipoproteins. BCO = p-carotene 15,15 -oxygenase. BCO2 = p-carotene 9, 10 -oxygenase. LPL = lipoprotein lipase. RBP = retinol binding protein. SR-BI = scavenger receptor class B, type I. 

Reboul, E. et al.. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type 1 (SR-Bl), Biochem. J., 387, 455, 2005. 

Altmann, S.W. et al.. The identification of intestinal scavenger receptor class B, type 1 (SR-Bl) by expression cloning and its role in cholesterol absorption, Biochim. Biophys. Acta, 1580, 77, 2002. 

Krieger, M, 2001. Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest 108, 793-797. 

Reboul, E, Klein, A, Bietrix, F, Gleize, B, Malezet-Desmoulins, C, Schneider, M, Margotat, A, Lagrost, L, Collet, X, and Borel, P, 2006. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J Biol Chem 281, 4739 4745. 

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... 

In summary, Caco-2 cells studies strongly suggest that carotenoids interact with each other at the level of cellular uptake by the enterocyte. This phenomenon has been explained by the fact that the uptake of several carotenoids involves, at least in part, the same intestinal membrane transporter the scavenger receptor class B type ISR-BI (Reboul et al. 2005, van Bennekum et al. 2005, Moussa et al. 2008). 

Moussa, M. et al. (2008). Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Nienmann-Pick Cl-like 1. J. Nutr. 138 1432-1436. 

X.-A. Li, W. B. Titlow, B. A. Jackson, N. Giltiay, M. Nikolova-Karakashian, A. Uittenbogaard, and E. J. Smart. High Density Lipoprotein Binding to Scavenger Receptor, Class B, Type I Activates Endothelial Nitric-oxide Synthase in a Ceramide-dependent Manner. J. Biol. Chem. 277 11058-11063 (2002). 

K. Hirano, S. Yamashita, Y. Nakagawa, T. Ohya, F. Matsuura, T. Tsukamoto, Y. Okamoto, A. Matsuyama, K. Matsumoto, J. Miyagawa and Y. Matsuzawa, Expression of human scavenger receptor class B type I in cultured human monocyte-derived macrophages and atherosclerotic lesions, Circ. Res. 85 (1999) 108-116. 

Gu X. J., Trigatti B., Xu S. Z., Acton S., Babitt J. and Krieger M. (1998) The efficient cellular uptake of high density lipoprotein lipids via scavenger receptor class B type I requires not only receptor-mediated surface binding but also receptor-specific lipid transfer mediated by its extracellular domain. J. Biol. Chem. 273, 26338-26348. 

Liu B. and Krieger M. (2002) Highly purified scavenger receptor class B, type I reconstituted into phosphatidylcholine/cholesterol liposomes mediates high affinity high density lipoprotein binding and selective lipid uptake. J. Biol. Chem. 277, 34125-34135. 

Reaven E., Leers-Sucheta S., Nomoto A. and Azhar S. (2001) Expression of scavenger receptor class B type 1 (SR-BI) promotes microvillar channel formation and selective cholesteryl ester transport in a heterologous reconstituted system. Proc. Natl. Acad. Sci. USA 98, 1613-1618. 

Scarselli E., Ansuini H., Cerino R., Roccasecca R. M., Acali S., Filocamo G., Traboni C., Nicosia A., Cortese R. and Vitelli A. (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J. 21, 5017-5025. 

Mardones P, Strobel P, Miranda S, Leighton F, Quinones V, Amigo L, Rozowski J, Krieger M, and Rigotti A (2002) Alpha-tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-BI)-deficient mice. Journal of Nutrition 132,443-9. 

Goti D, Hrzenjak A, Levak-Frank S, Frank S, van der Westhyzen DR, et al. 2001. Scavenger receptor class B, type I is expressed in porcine brain capillary endothelial cells and contributes to selective uptake of HDL-associated vitamin E. J. Neurochem. 76(2) 498-508... 

Silver DL, Tall AR. 2001. The cellular biology of scavenger receptor class B type I. Curr. Opin. Lipidol. 12 497-504... 

Figure 18-16 depicts a model for the selective uptake of cholesteryl esters by a cell-surface receptor called SR-BI (scavenger receptor, class B, type I). SR-BI binds HDL, LDL, and VLDL and can mediate selective uptake from all of these lipoproteins. The detailed mechanism of selective llpid uptake has not yet been elucidated, but It may entail hemifuslon of the outer phospholipid monolayer of the lipoprotein and the exoplasmic leaflet of the plasma membrane. The cholesteryl esters Initially enter the hydrophobic center of the plasma membrane, are subsequently transferred across the Inner leaflet, and are eventually hydrolyzed by cytosolic, not lysosomal, cholesteryl esterases. The llpid-depleted particles remaining after llpid transfer dissociate from SR-BI and return to the circulation they can then extract more phospholipid and cholesterol from other cells by means of the ABCAl protein or other cell-surface transport proteins (see Figure 18-13c). Eventually, small llpid-depleted HDL particles circulating In the bloodstream are filtered out by the kidney and bind to a different receptor on renal epithelial cells. After these particles have been Internalized by receptor-mediated endocytosis, they are degraded by lysosomes.

Zhang, Y., Da Silva, J.R., Reilly, M., Billheimer, J.T., Rothblat, G.H., Rader, D.J. 2005. Hepatic expression of scavenger receptor class B type I (SR-BI) is a positive regulator of macrophage reverse cholesterol transport in vivo. J. Clin. Invest. 115 2870-2874. 

Mineo C, Shaul PW. Functions of scavenger receptor class B, type I in atherosclerosis. 

The measurement of the uptake kinetics indicated that high-density lipoprotein might be the primary source of the vitamin E uptake by type II pneumocytes (Kolleck et al. 1999). Vitamin E depletion of rats caused an increase of vitamin E uptake by isolated type II pneumocytes from high-density hpoprotein but not from low-density lipoprotein or very low-density lipoprotein. Type II pneumocytes express the scavenger receptor class B type 1 (SR-Bl), a high-density lipoprotein-specific receptor. Vitamin E depletion caused an increased expression of SR-Bl by a post-transcriptional mechanism. The increased vitamin E uptake from high-density lipoprotein and the increased expression of the SR-Bl were reversed by refeeding the vitamin. 

Scavenger receptor class B type 1 (SR Bl) facilitates the efflux of cholesterol in peripheral tissues to HDL and mediates the selective uptake of CE from HDL in the liver. SR B1 deficiency in mice is associated with deregulation of cholesterol homeostasis in the arterial wall, resulting in increased susceptibility to atherosclerosis with increased expression of inflammatory markers and lipid deposition in the aorta (480). Inflammatory mediators down regulate SR Bl in macrophages (481). 

Malerod L, Sporstol M, Juvet LK, et al. Hepatic scavenger receptor class B, type 1 is stimulated by peroxisome proliferator-activated receptor gamma and hepato-cyte nuclear factor 4alpha. Biochem Biophys Res Commun 2003 305 557-565. 

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