Low-density lipoprotein receptor LDLR

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. 

Fig. 5.2.6 Long-distance polymerase chain reaction (PCR) to detect large deletions and insertions in the low-density lipoprotein receptor (LDLR). The structure of the LDLR gene is shown from exon 1 through 18. The five fragments produced by the five long-distance PCRs are outlined. PCR1 covers exons 1-5, PCR2 exons 6-13, PCR3 exons 15-18, PCR 4 exons 2-10, and PCR5 exons 12-18...

Low-density lipoprotein receptor LDLR C16730T P-blocker 0.006... 

This theme has been developed by studies of receptor—virus interactions for low-density lipoprotein receptor (LDLR), the receptor for a minor receptor group rhinovirus HRV-2 (Hewat et al, 2000), and the glycolipid globoside bound to human parvovirus (Chipman et al, 1996). Both of these receptors are small and globular and bind at different positions on the viral surface. In the case of LDLR, binding is at a star-shaped dome... 

Whereas ICAM-1 clearly mediates attachment and infection of the major group of HRVs, the human low-density lipoprotein receptor (LDLR) has been identified as the receptor for the minor group of rhinoviruses, including HRV2 (Hofer et al, 1994). The LDLR appears to mediate internalization of HRV2 via a classic endocytic pathway. Subsequently, the transfer of viral RNA occurs from the endosome/late endosome through a pore in the endosomal membrane (Prchla et al, 1995). 

Low density lipoprotein receptor (LDLR) LDL, Flaviviridae viruses TM... 

Apolipoprotein E (apoE) is an important lipid transport protein in human plasma and brain. It mediates hepatic clearance of remnant lipoproteins as a high-affin-ity ligand for the low-density lipoprotein receptor (LDLR) family, including LDLR, LDLR-related protein (LRP), and cell surface heparan sulfate PGs (71). In the liver, heparan sulfate PGs facilitate the interaction of remnant particles with LRP, which is known as the heparan sulfate PG-LRP pathway, in which apoE initially interacts... 

In a mechanism distinct from that of the statin drugs, berberine can significantly reduce plasma levels of LDL cholesterol. The mechanism involves upregulation of the low-density lipoprotein receptors (LDLR) in the liver. The LDL receptor system coordinates cholesterol metabolism, allowing excessive LDL cholesterol to be cleared from the bloodstream (Goldstein and Brown 2009). Berberine was... 

Diet, genetic inheritance, or both may cause hypercholesterolemia (high cholesterol). Familial hypercholesterolemia is caused by mutations in several genes. These mutations cause a decrease in the number of low-density lipoprotein receptors (LDLR), the main carrier of cholesterol in the blood. The condition is more prevalent in Afrikaner, Finnish, French Canadian, and Lebanese populations. However, the majority of hypercholesterolemia is caused by lifestyle choices—diet, exercise, and smoking. (USNLM, 2007). 

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). 

Heath KE, Gahan M, Whittall RA, Humphries SE. Low-density lipoprotein receptor gene (LDLR) world-wide website in familial hypercholesterolaemia update, new features and mutation analysis. Atherosclerosis 2001 154 243-246. 

LDLR low density lipoprotein receptor MVB multivesicular body... 

Human rhinoviruses (HRV) are members of the Picornaviridae family. The HRVs are classified according to their receptor specificity into members of the major and minor groups. The 87 members of the major-group viruses bind to the intracellular adhesion molecule receptor 1 (ICAM-1), whereas the 12 serotypes of the minor group bind to members of the low-density lipoprotein receptor family (LDLR) [42]. Rhinoviruses cause more than a billion cases of the common cold each year and are also associated with asthma exacerbations [43,44]. Statistically, one encounters one to three infections per year on the average [45]. As a result, rhinoviral infections are responsible for 25 million days of missed work in the USA [46]. 

Figure 15-2. A simplified schematic of cholesterol transport. Cholesterol travels to non-hepatic cells, such as the macrophage, via VLDL and LDL particles, while excess cholesterol is shuttled to the liver via HDL particles. Note that AHCAl mediates nascent HDL formation by translocating cellular cholesterol and phospholipids to apolipoprotein A-I (apoA-I) in an active, energy-dependent reaction. CETP, cholesteryl ester transfer protein LCAT, lecithinxholesterol acyltransferase LDLR, low-density lipoprotein receptor SR-B1, scavenger receptor Bl.

Fig. 30.5. Endogenous and exogenous pathways for lipid transport and metabolism. FFA, free fatty acids LDLR, low-density lipoprotein receptor FC, free unesterified cholesterol LCAT, lecithin-cholesterol acyltransferase.

LD50/ED50 ratio, 1508 LDL. See Low-density lipoproteins (LDL) LDLR. See Low-doisity lipoprotein receptor (LDLR)... 

Fig. 5.2.1 The major metabolic pathways of the lipoprotein metabolism are shown. Chylomicrons (Chylo) are secreted from the intestine and are metabolized by lipoprotein lipase (LPL) before the remnants are taken up by the liver. The liver secretes very-low-density lipoproteins (VLDL) to distribute lipids to the periphery. These VLDL are hydrolyzed by LPL and hepatic lipase (HL) to result in intermediate-density lipoproteins (IDL) and low-density lipoproteins (LDL), respectively, which then is cleared from the blood by the LDL receptor (LDLR). The liver and the intestine secrete apolipoprotein AI, which forms pre-jS-high-density lipoproteins (pre-jl-HDL) in blood. These pre-/ -HDL accept phospholipids and cholesterol from hepatic and peripheral cells through the activity of the ATP binding cassette transporter Al. Subsequent cholesterol esterification by lecithinxholesterol acyltransferase (LCAT) and transfer of phospholipids by phospholipid transfer protein (PLTP) transform the nascent discoidal high-density lipoproteins (HDL disc) into a spherical particle and increase the size to HDL2. For the elimination of cholesterol from HDL, two possible pathways exist (1) direct hepatic uptake of lipids through scavenger receptor B1 (SR-BI) and HL, and (2) cholesteryl ester transfer protein (CfiTP)-mediated transfer of cholesterol-esters from HDL2 to chylomicrons, and VLDL and hepatic uptake of the lipids via the LDLR pathway...

C, cholesterol LDL, low-density lipoprotein LDLR, LDL receptor, VLDL, very low density lipoprotein. 

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