Lipoprotein receptors regulation

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. 

Salleh MN, Runnie I, Roach, PD, Mohamed S and Abeywardena MY. 2002. Inhibition of low-density lipoprotein oxidation and up-regulation of low-density lipoprotein receptor in HepG2 cells by tropical plant extracts. J Agric Food Chem 50(13) 3693-3697. 

Sirtori, C.R., Galli, G., Lovati, M.R., CXarrara, P., Bosisio, E. and Kienle, M.G. (1998). Effects of dietary proteins on regulation of liver lipoprotein receptors in rats, J. Clin. Nutr., 114, 1493-1500. 

G. Martin, A. Pilon, C. Albert, M. Valle, D.W. Hum, J.C. Fruehart, J. Najib, V. Clavey and B. Staels, Comparison of expression and regulation of the high-density lipoprotein receptor SR-BI and the low-density lipoprotein receptor in human adrenocortical carcinoma NCI-H295 cells, Eur. J. Biochem. 261 (1999) 481-491. 

Apolipoproteins help maintain the structural integrity and solubility of the lipoprotein complexes, and aid in lipoprotein receptor recognition and regulation of certain enzymes in lipoprotein metabolism. 

El-Sohemy A, Archer MC. Regulation of mevalonate synthesis in low density lipoprotein receptor knockout mice fed n-3 or n-6 polyunsaturated fatty acids. Lipids 1999 34 1037-1043. Nakamura N, Hamazaki T, Jokaji H, Minami S, Kobayashi M. Effect of HMG-CoA reductase inhibitors on plasma polyunsaturated fatty acid concentration in patients with hyperlipidemia. Int. J. Clin. Lab. Res. 1998 28 192-195. 

Other Activities. IFNy causes a concentration-dependent decrease in steady-state lipoprotein receptor-related protein (LRP) mRNA expression and gene transcription rate. When TGFpl is added 24 hours before IFNy, the extent of LRP down regulation is reduced. This suggests... 

Gibori, G., Chen, Y.-D.L, Khan, I., Azhar, S., and Reaven, G.M. (1984). Regulation of luteal cell lipoprotein receptors, sterol contents, and steroidogenesis by estradiol in the pregnant rat. Endocrinology 7(4 609-617. 

Receptors Cells or tissues Lipoproteins bound Ligands involved Receptor regulation Functional roles... 

May, R, Reddy, Y.K., Herz, J. 2002. Proteolytic processing of low density lipoprotein receptor-related protein mediates regulated release of its intracellular domain. J. Biol. Chem. 277 18736-18743. 

Trypanosoma cruzi expresses a neuraminidase activity which is developmentally regulated. Enzyme aetivity is maximal in infective trypomastigotes, 10 to 560 times less in epimastigotes, and is absent in amastigotes. The neuraminidase, of an apparent moleeular mass of 160-200 kDa, is located on the outer membrane and is released by a stage-specifie phospholipase C. Of interest is the presence of sequences similar to low-density lipoprotein receptor and to the type III module of fibronectin (14). 

Li YH, Yang P, Kong WJ et al (2009) Berberine analogues as a novel class of the low-density-lipoprotein receptor up-regulators synthesis, structure-activity relationships, and cholesterol-lowering efficacy. J Med Chem 52(2) 492-501... 

Applebaum-Bowden, D., Haffner, S.M., Hartsook, E., Luk, K.H., Albers, J.J. andHazzard, W.R. (1984) Down-regulation of the low-density lipoprotein receptor by dietary cholesterol. Am. J. Clin. Nutr. 39, 360-367. 

The role of NFkB has been reviewed in ref. 205. NFkB is a key regulator of inflammation, immune responses, cell survival, and cell proliferation inhibition of the NFkB pathway in macrophages leads to more severe atherosclerosis in low density lipoprotein receptor (LDLR) deficient mice, possibly by affecting the pro- and anti-inflammatory balance that controls the development of atherosclerosis (reduced production of LPS-stimulated TNF, and reduction in IL-10) (206). 

Herboxidiene 154 shows potent herbicidal activity and up-regulates gene expression of low density lipoprotein receptors. Kocienski and coworkers synthesized herboxidiene 154 successfully from two key fragments using a modified Julia olefmation based on the benzothiazolyl sulfone activator. The yield was 81% with excellent selectivity 0E Z = 91 9) by one-port reaction between sulfone 152 and the aldehyde 151. 1-Phenyl-1/f-tetrazolyl sulfone 149 was used as activator in the synthesis of the C -Cio oxane fragment 151. Addition of KHMDS to the mixture of sulfone 149 and aldehyde 148 in 1,2-dimethoxyethane at -60 °C gave a 93% yield of the alkene 151 with good stereoselectivity (E Z = 93 1). 

The reason for the cholesterol-lowering effect of polyunsaturated fatty acids is still not fully understood. It is clear, however, that one of the mechanisms involved is the up-regulation of LDL receptors by poly-and monounsaturated as compared with saturated fatty acids, causing an increase in the catabolic rate of LDL, the main atherogenic lipoprotein. In addition, saturated fatty acids cause the formation of smaller VLDL particles that contain relatively more cholesterol, and they are utilized by extrahepatic tissues at a slower rate than are larger particles—tendencies that may be regarded as atherogenic. 

As an example, the low-density lipoprotein (LDL) molecule and its receptor (Chapter 25) are internalized by means of coated pits containing the LDL receptor. These endocytotic vesicles containing LDL and its receptor fuse to lysosomes in the cell. The receptor is released and recycled back to the cell surface membrane, but the apoprotein of LDL is degraded and the choles-teryl esters metabolized. Synthesis of the LDL receptor is regulated by secondary or tertiary consequences of pinocytosis, eg, by metabolic products—such as choles-... 

Peroxisome-proliferator activated receptors (PPARs) are lipid-activated transcription factors exerting several functions in development and metabolism. PPARa is implicated in the regulation of lipid metabolism, lipoprotein synthesis, and inflammatory response in liver and other tissues. 

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