Lipoproteins receptors

LRP is a member of the LDL receptor gene family (ref. 649) and, like the LDL receptor, performs an essential role in the removal of certain lipoprotein particles from the bloodstream. As Heeren et al. (ref. 650) explain, triglycerides are transported mainly by two distinct classes of lipoproteins, the chylomicrons and the very-low-density lipoproteins (VLDL). After assembly in the intestine, chylomicrons are carried via lymph into the bloodstream, where they are transformed at the endothelial surface to remnant lipoproteins through the catalytic action of lipoprotein lipase (for review, see ref. 651,652). After lipolysis, the lipoprotein lipase remains associated with the chylomicron remnants and, in conjunction with apolipoprotein E (apo E) (ref. 653-655), facilitates their clearance by the liver into hepatocytes (ref. 656) via LDL receptors and the LRP (ref. 657-660). (The essential role for both receptors in chylomicron remnant removal in vivo has been demonstrated in gene knockout and gene transfer experiments (ref. 661,662 for review, see ref. 663).) 

The remarkable rapidity and specificity of uptake of the chylomicron remnant particles is believed to be highly dependent on their acquisition of apo E in the bloodstream (ref. 664,665) the critical role played by apo E in directing the clearance of chylomicron remnants from the (blood) plasma has been well 

The chylomicron remnant particles themselves, derived from lipolysis of the larger chylomicrons (cf. above), contain the residual triglyceride and all of the cholesterol and cholesterol ester from the original chylomicrons. This lipid composition of the chylomicron remnant particles is similar to the above-described lipid composition of both LDL particles (cf. Section 14.1) and LCM (cf. Section 12.1). Based upon this molecular similarity, it appears reasonable to expect that injected LCM could also readily bind apo E (i.e., as an alternative to apo B) in the bloodstream. In this case, the proposed LCM binding of apo E should influence the subsequent biodistribution of those LCM via two endocytic pathways specifically, one pathway mediated by the LDL receptor (a.k.a. apo B,E receptor ) (cf. Section 14.1) and the other pathway mediated by the LRP, since both receptor types have a high affinity for apo E (cf. above). 

Another major type of tumor cell examined for the presence of LRP was human breast cancer cells. Li et al. (ref. 670) examined six breast cancer cell lines and showed that LRP is expressed at a wide range of levels, i.e., approximately 300 to 6,300 sites per cell. Four of the breast cancer cell lines expressed LRP at over 1,000 sites per cell, and were markedly invasive in their assay (ref. 670). 

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Proteins embedded in the shell of lipoproteins. They serve as scaffold for assembly of the lipoprotein particle in the endoplasmic reticulum. In addition, they control metabolism of lipoproteins in the circulation by interaction with enzymes such as lipases. Finally, apolipoproteins determine cellular uptake of the particles by interaction with specific lipoprotein receptors expressed on the surface of target cells. 

Low-density Lipoprotein Receptor Gene Family Growth Factors... 

HMG-COA-Reductase Inhibitors Low-Density Lipoprotein Receptor Gene Family... 

Very low-density lipoprotein receptor ( VLDLR) and APOE receptor-2 ( APOER2) are two gene family members with redundant functions. They are expressed in neurons of the developing brain and act as cell... 

Low-density Lipoprotein Receptor Gene Family. Table 1 Human diseases of the LDL receptor gene family... 

Nykjaer A, Willnow TE (2002) The low-density lipoprotein receptor gene family a cellular Swiss army knife Trends Cell Biol 12 273-280... 

Herz J, Chen Y (2006) Reelin, lipoprotein receptors and synaptic plasticity. Nat Rev 7 850-859... 

Andersen OM, Willnow TE (2006) Lipoprotein receptors in Alzheimer s disease. Trends Neurosci 29 687-694... 

Reelin is an extracellular matrix protein, which is secreted by neuronal cells and binds to two lipoprotein receptors (VLDLR and ApoER2) that relay the Reelin signal inside target neurons by docking the tyrosine kinase adapter disabled-1 (Dabl). This allows neurons to complete migration and adopt their ultimate positions in laminar structures in the central nervous system. In... 

Douglas SD (2001) Methadone may promote HIV replication study. AIDS Alert 16 120 Dreyer EB, Kaiser PK, Offermann IT, Lipton SA (1990) HIV-1 coat protein neurotoxicity prevented by calcium channel antagonists. Science 248 364-367 Dunn S, Vohra RS, Murphy JE, Homer-Vanniasinkam S, Walker JH, Ponnambalam S (2008) The lectin-like oxidized low-density-lipoprotein receptor a pro-inflammatory factor in vascular disease. Biochem J 409 349-355... 

Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6 1380-1387... 

BAUM J A, TENG H, ERDMAN J W Jr, WEIGEL R M, KLEIN B P, PERSKY V W, FREELS S, SURYA P, BAKHIT R M, RAMOS E, SHAY N F and POTTER s M (1998) Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density-lipoprotein receptor messenger RNA in hypercolesterolemic postmenopausal women. Am J Clin Nutr. 68 (3) 545-51. 

Using human hepatoma-derived cell lines Kong et al. [268] showed that berberine increased mRNA and protein as well as the function of hepatic linear low density lipoprotein receptor (LDLR). It does not stimulate the transcription of LDLR, as the LDLR promoter activity was not increased by this compound. Post-transcriptional regulation appears to be the main working mechanism underlying the effect of this alkaloid on LDLR expression. It was proposed that berberine can be used as a monotherapy to treat hypercholes-terolemic patients [268]. Very recently it was observed [269] that berberine reduces cholesterol and Upid accumulations in plasma as well as Uver. 

Gu L, Okada Y, Clinton SK, et al. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998 2 275-81. 

Ishibashi S, Goldstein JL, Brown MS, Herz J, Bums DK. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 1994 93(5) 1885—1893. 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

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