Lipoprotein uptake

RPE expresses several receptors responsible for lipoprotein uptake, including lipoprotein receptors LDL receptor (LDLR) (Tserentsoodol et al., 2006b), VLDL receptor (VLDLR) (Hu et al., 2008), as... 

These data suggest that one of possible mechanisms of carotenoid delivery to the neural retina may involve lipoprotein uptake from the basal side of the RPE followed by its retro-endocytosis on the apical site (Lorenzi et al., 2008). Alternatively, the endocytosed lipoprotein may be degraded in the RPE followed by secretion of certain lipophilic components from the lipoprotein at the apical site. Due to low solubility of carotenoids in aqueous solutions, it may be suggested that they are secreted already bound to a protein or that an acceptor protein is available in the interphotoreceptor matrix and/or POS. 

The uneven but wide tissue distribution of most dietary carotenoids may indicate an active biological role for these compounds (see Chapter 20). The organs with the greatest number of low-density lipoprotein (LDL) receptors and the highest rates of lipoprotein uptake (adrenals, testes, and liver)... 

Grove RI, Mazzucco C, Allegretto N, et al. Macrophage-derived factors increase low-density lipoprotein uptake and receptor number in cultured human liver cells. J Lipid Res 1991 32 1889-1897. 

M. G. Irving, F. J. Roll, S. Huang, and D. M. Bissell, Characterization and culture of sinusoidal endothelium from normal rat fiver Lipoprotein uptake and collagen phenotype, Gastroenterology 697 239-246 (1995). 

Ignatius Ml, Shooter EM, Pitas RE, Mahley RW (1987) Lipoprotein uptake by neuronal growth cones in vitro. Science 236 959-962. 

Zwaka TP, Hombach V, et al. C-reactive protein-mediated low density lipoprotein uptake by macrophages implications for atherosclerosis. Circulation 2001 103 1194-7. 

While these events were first described for LDL uptake, they may represent a general mechanism for receptor-mediated lipoprotein uptake by all lipoprotein receptors (for reviews, see refs. 10, 12, 22, 26 and 27). 

While the events in receptor-mediated lipoprotein uptake are best characterized for the LDL receptor, they probably are representative of common mechanisms for the receptor-mediated endocytosis of other lipoproteins as well as for many other nonlipoprotein ligands. Individual lipoprotein receptor systems appear to differ primarily with respect to the lipoproteins recognized and the regulatory events which follow internalization and degradation. 

The only receptor-mediated uptake process regulated in macrophages involves suppression of )8-VLDL receptors. This suppression only occurs after extensive cholesterol ester accumulation and can be induced by either j8-VLDL or chemically modified LDL [13]. Lipoprotein uptake by all known receptor systems in macrophages causes a marked stimulation of ACAT activity which results in the massive accumulation of cholesteryl ester droplets in the cytoplasm [13]. Free cholesterol can be excreted from the macrophage if cholesterol-accepting Upoproteins such as HDL are present. The uncontrolled uptake and deposition of cholesteryl esters in macrophages is believed to be the key to formation of the foam cells which are associated with atherosclerosis. 

In contrast to the extensive literature on the regulation of intestinal cholesterol synthesis, only a few studies are available on regulation of lipoprotein uptake in this organ. Notably, recent studies have compared the effect of various interventions such as the feeding of cholesterol, cholestyramine, surfomer, and com oil on both rates of cholesterol synthesis and LDL transport in the rat intestine in vivo, as shown in Fig. 9. While these various manipulations all alter rates of cholesterol synthesis, there is no consistent effect upon LDL uptake at any location in the mucosa, with the possible exception of a slight increase in the jejunum after feeding... 

Zwaka, T.P., Hombach, V., and Torzewski, J. (2001) C-Reactive Protein-Mediated Low-Density Lipoprotein Uptake by Macrophages—Implications for Atherosclerosis, Circulation 103,1194-1197. 

Kuda, O., Pietka, T.A., Demianova, Z., Kudova, E., Cvacka, J., Kopecky, J. Abumrad, N.A. Sulfo-A -succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164 SSO also inhibits oxidized low density lipoprotein uptake by macrophages. J. Biol. Chem. 2013, 288 15547-15555. 

Lipid homeostasis is dependent on the interaction between receptor mediated and enzymatic reactions that regulate cholesterol and triglycerides. Receptor mediated lipoprotein uptake occurs through different mechanisms ... 

The enhancement of receptor-mediated-TG-rich lipoprotein uptake is multifactorial. Two very important factors include conformational changes in apoproteins resulting in increased affinity for LDL receptor (362), and loss of Apo C (361). Apo Cl acts by interfering with Apo E-mediated lipoprotein uptake, but Apo Cl also has actions independent of Apo E (370). 

More general information about the potential role of apoE in cellular lipoprotein uptake has come from studies with cultured cells (e.g., fibroblasts). Such cells manifest surface receptors for LDL that bind apoB, the protein component of LDL. This is followed by receptor-mediated endocytosis, fusion of the endo-cytic vesicles with lysosomes, and LDL degradation within the lysosomes (see Goldstein and Brown, 1979 Brown et al., 1981, for reviews and references). Cholesteryl esters taken into cells in this manner are hydrolyzed by a lysosomal acid lipase. The liberated cholesterol then leaves the lysosome and is used in the cell for membrane synthesis and as a regulator of intracellular cholesterol homeostasis. 

Aviram M, Bias K. Dietary olive oil reduces low-density lipoprotein uptake by macrophages and decreases the susceptibility of the lipoprotein to undergo lipid peroxidation. Ann Nutr Metah 1993 37 75-84. 

Ismail NA, Alavi MZ and Moore S. Lipoprotein-proteoglycan complexes from injured rabbit aortas accelerate lipoprotein uptake by arterial smooth muscle cells. Atherosclerosis 105 79-87, 1994. 

Vitamin E is delivered to tissues by three mechanisms transfer from triglyceride-rich lipoproteins during lipolysis as a result of tissue lipoprotein uptake by various receptors that mediate lipoprotein uptake and as a result of vitamin E exchange between lipoproteins or tissues. The regulation of tissue vitamin E is not well understood, but a-tocopherol is the predominant form in tissues as a result of its dominance in plasma. 

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