Apolipoprotein E and

Fig. 9-4). Very low-density lipoprotein particles are released into the circulation where they acquire apolipoprotein E and apolipoprotein C-II from HDL. Very-low density lipoprotein loses its triglyceride content through the interaction with LPL to form VLDL remnant and IDL. Intermediate-density lipoprotein can be cleared from the circulation by hepatic LDL receptors or further converted to LDL (by further depletion of triglycerides) through the action of hepatic lipases (HL). Approximately 50% of IDL is converted to LDL. Low-density lipoprotein particles are cleared from the circulation primarily by hepatic LDL receptors by interaction with apolipoprotein B-100. They can also be taken up by extra-hepatic tissues or enter the arterial wall, contributing to atherogenesis.4,6... 

Bickeboller H, Campion D, Brice A, Amouyel P, Hannequin D, Didierjean O et al. Apolipoprotein E and Alzheimer disease genotype-specific risks by age and sex. Am J Hum Genet 1997 ... 

Ordovas JM, Lopez-Miranda J, Perez-Jimenez F, Rodriguez C, Park JS, Cole T, et al. Effect of apolipoprotein E and A-IV phenotypes on the low density lipoprotein response to HMG CoA reductase inhibitor therapy. Atherosclerosis 1995 113 157-166. 

Neuroanatomical and neuropathological basis of Alzheimer s disease Histological features of Alzheimer s disease include neuritic plaques and neurofibrillary tangles (Boiler and Duyckaerts 1997). Neuritic plaques are composed of extracellular deposits of j8-amyloid protein and apolipoprotein E and are found primarily in neocortex. j8-amyloid is derived from an amyloid precursor protein, and is suspected to be a chief causal factor in Alzheimer s disease pathology (Samuel et al. 1997). Neurofibrillary tangles are clusters of protein fibers found in the cell body and composed of tau protein, which normally serves as a cytoskeletal element. Neurofibrillary tangles progress from entorhinal cortex to hippocampus, and then to neocortical areas. 

Figure 5.12 Receptor-mediated endocytosis of the LDL particle. The specificity of binding depends upon two proteins that are components of the LDL particle, apolipoprotein E and apolipoprotein B (Chapter 11).

Smelt AH, de Beer F (2004) Apolipoprotein E and familial dysbetalipoproteinemiaxlinical, biochemical, and genetic aspects. Semin Vase Med 4 249-257... 

As mentioned in Chapter 21, there are several related receptors with similar structures. Two of them have a specificity for apolipoprotein E and can accept remnants of VLDL particles and chylomicrons.216 220 The LDL receptor-related protein is a longer-chain receptor.216 221 LDL particles, especially when present in excess or when they contain oxidized lipoproteins, may be taken up by endocytosis into macrophages with the aid of the quite different scavenger receptors.221 225 The uptake of oxidized lipoproteins by these receptors may be a major factor in promoting development of atherosclerosis (Box 22-B). On the other hand, scavenger receptor SR-B1, which is also present in liver cells, was recently identified as the receptor for HDL and essential to the "reverse cholesterol transport" that removes excess cholesterol for excretion in the bile.213/213a... 

Similarly, apolipoprotein E expression increases in neurotoxicity mediated by KA (Table 6.3) (Boschert et al., 1999). Apolipoprotein E is a major lipoprotein in the brain. It is involved in the transport, distribution, and other aspects of cholesterol homeostasis. Apolipoprotein E also plays a dominant role in the mobilization and redistribution of brain lipids in repair, growth, and maintenance of nerve cells (Mahley, 1988). The secretion of apolipoproteins E and D may be differentially regulated in cultured astrocytes. In cell culture systems this depends upon the extracellular lipid milieu (Patel et al., 1995). During neurotoxicity mediated by KA, apolipoprotein E levels increase moderately in astrocytes and apolipoprotein E mRNA increases very strongly in clusters of CA1 and CA3 pyramidal neurons. Based on hybridization in situ and immunohistochemical studies, expression of apolipoprotein E in neurons may be a part of a rescue program to counteract neurodegeneration mediated by KA (Boschert et al., 1999). 

J. Heeren, T. Grewal, S. Jackie and U. Beisiegel, Recycling of apolipoprotein E and lipoprotein lipase through endosomal compartments in vivo, J. Biol. Chem. 276 (2001) 42333-42338. 

Curtiss LK, Boisvert WA. Apolipoprotein E and atherosclerosis. Curr Opin Lipidol 2000 11 243-251. 

Kervinen K, Savolainen MJ, Salokannel J, Hynninen A, Heikkinen J, Ehnholm C, Koistinen MJ, Kesaniemi YA. Apolipoprotein E and B polymorphisms—longevity factors assessed in nonagenarians. Atherosclerosis 1994 105 89-95. 

W17. Windier, E., Chao, Y., and Havel, R. J., Regulation of the hepatic uptake of triglyceride-rich lipoproteins in the rat. Opposing effects of homologous apolipoprotein E and individual C apoproteins. J. Biol. Chem. 255, 8303-8307 (1980). 

Pitas RE, Boyles JK, Lee SH, Foss D, Mahley RW (1987) Asd oeytes syndiesize apolipoprotein E and metabolize apolipoprotein E-con-taining lipoproteins. Biochim Biophys Acta 917 148—161. 

Saura J, Petegnief V, Wu X, Liang Y, Paul SM (2003) Microglial apolipoprotein E and astroglial apolipoprotein J expression in vitro Opposite effects of lipopolysaccharide. J Neurochem 85 1455-1467. 

Mori K, Yokoyama A, Yang L, Maeda N, Mitsnda N, Tanaka J (2004) L-serine-mediated release of apolipoprotein E and lipids from microgbal cells. Exp Nenrol 185 220-231. 

Okochi M, Tagami S et al (2010) Apolipoprotein E and central nervous system disorders Reviews of clinical findings. 

C-III, and phospholipids are transferred to EfDL. Apolipoproteins E and C-II are transferred to chylomicrons from EfDL and evenmally back through these metabolic events. Hepatic VLDL synthesis is regulated in part by diet and hormones and is inhibited by uptake of chylomicron remnants in the liver. VLDL is secreted from the Ever and serially converted via LPL to intermediate-density hpoprotein (IDL) and finally to LDL. VLDL receptors are found in adipose tissue and muscle and bear close homology to the structure of LDL receptors. 

Christensen DJ, Ohkubo N, Oddo J et al (2011) Apolipoprotein E and peptide mimet-ics modulate inflammation by binding the SET protein and activating protein phosphatase 2A. J Immunol 186 2535-2542... 

Roses, A. D., A model for susceptibility polymorphisms for complex diseases apolipoprotein E and Alzheimer disease. Neurogenetics, 1997. 1(1) p. 3-11. 

Djousse, L., Myers, R.H., Coon, H., Arnett, D.K., Province, M.A., and Ellison, R.C. (2000) Smoking Influences the Association Between Apolipoprotein E and Lipids The National Heart, Lung, and Blood Institute Eamily Heart Study, Lipids 35, 827-831. 

Campos, H., D Agostino, M., and Ordovas, J.M. (2001) Gene-Diet Interactions and Plasma Lipoproteins Role of Apolipoprotein E and Habitual Saturated Fat Intake, Genet. Epidemiol. 20, 117-128. 

Takahashi, S., Suzuki, J., Kohno, M., Oida, K., Tamai, T., Miyabo, S., Yamamoto, T. Nakai, T. (1995) J-Biol-Chem, 270, 15747-15754. Enhancement of the binding of triglyceride-rich lipoproteins to the very low density lipoprotein receptor by apolipoprotein E and lipoprotein lipase. 

Another application of heparin affinity chomatography was reported by Trezzi et al. [9]. They separated very low density lipoproteins (VLDL) into four subfractions, which they named A, B, C and D. Only fractions C and D contained measurable amounts of apolipoprotein E, and only these two subfractions interacted with human fibroblasts. 

Chiwata T, Aragane K, Fujinami K, et al. Direct effect of an acyl-CoAxholesterol acyltransferase inhibitor, F-1394, on atherosclerosis in apolipoprotein E and low density lipoprotein receptor double knockout mice. Br J Pharmacol 2001 133 1005-1012. 

Mirabella M, Alvarez RB, Engel WK et al. (1996) Apolipoprotein E and apoUpoprotein E messenger RNA in muscle of inclusion body myositis and myopathies. Ann Neurol 40, 864-872. 

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