Effect of cholesterol

Effect of Cholesterol. Cholesterol inclusion into the lipid bilayers composed of DPPC or DSPC, eliminates apparent Tc and reduces permeability at and above the usual Tc. On the other hand, cholesterol inclusion increases packing of fluid bilayer composed of lipids with unsaturated fatty acyl chains. Since cholesterol rich liposomes are stable in plasma, cholesterol is commonly used as a liposomal component. 

The compensatory effect of cholesterol observed in D407 cells have also been demonstrated in other cell lines (Cho et al. 1998 Holleran et al. 1998) and may well be a consequence of tamoxifen-induced severe inhibition of lanosterol (to cholesterol)-converting enzymes. In rat liver preparations and CHO cells, sterol A8-isomerase (IC50 0.21-0.15. iM) was the most sensitive... 

Finkelstein, A. and Cass, A. (1967). Effect of cholesterol on the water permeability of thin lipid membranes, Nature, 216, 717-718. 

Pyrene has been used to investigate the extent of water penetration into micelles and to accurately determine critical micellar concentrations (Kalyanasundaram, 1987). Polarity studies of silica or alumina surfaces have also been reported. In lipid vesicles, measurement of the ratio Ii/Iui provides a simple tool for determination of phase transition temperatures and also the effect of cholesterol addition. 

Most of us are familiar with the effects of cholesterol. Exhibit 1.3 provides an explanation of how cholesterol is formed and the mechanism of action for Lipitor and Zocor in lowering the sterol. 

Figure 2 (A) Effect of incubation temperature on uptake of doxorubicin into 200 nm EPC/cholesterol (55 45 mol/mol) large unilamellar vesicles (LUVs) exhibiting a transmembrane pH gradient (pH 4 inside, 7.8 outside). Doxorubicin was added to LUVs (D/L = 0.3 wt wt) equilibrated at 21°C, 37°C, and 60°C. (B) Effect of cholesterol on the uptake of doxorubicin at 20 into lOOnm LUVs exhibiting a transmembrane pH gradient (pH 4.6 inside, 7.5 outside). Lipid compositions were EPC and EPC/cholesterol (1 1 mol/mol). The initial drug-to-lipid ratio was 100 nmol/pmol. Source Prom Refs. 12 (A), 21 (B).

Papahadjopoulos D, Nir S, Oki S. Permeability properties of phospholipid membranes effect of cholesterol and temperature. Biochim Biophys Acta 1972 ... 

B. S. Reddy and K. Watanabe, Effect of cholesterol metabolites and promoting effect of lithocholic acid in colon carcinogenesis in germ-free and conventional F344 rats. Cancer Res., 1979, 39, 1521. 

Heart Protection Study Collaborative Group. Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet 2004 363 757-67. 

MD simulations have provided a unique molecular description of cholesterol-phospholipid interactions [31]. Atomistic simulations have succeeded in reproducing the condensing effect of cholesterol on phospholipid bilayers [32-34], With atomistic detail, many properties can be determined, such as the effect of cholesterol on lipid chain ordering or on hydrogen bond formation. Other simulations have focused on the interaction of cholesterol and SM [35-37], Aittoniemi et al. [38] showed that hydrogen bonding alone cannot explain the preferential interaction between cholesterol and SM compared to cholesterol and POPC. 

We have also undertaken MD simulations to examine the effect of cholesterol content on the thermodynamics of DPPC desorption [54], We found that DPPC had a lower affinity for bilayers with high cholesterol content (Figure 3B). This suggests that while cholesterol prefers to interact with saturated lipid tails, the saturated tails might not prefer to interact with cholesterol. It would be interesting to repeat this study on unsaturated lipid tails. 

Mitchell, D.C., Litman, B.J. Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys. J. 1998, 75, 896-908. 

Kucerka, N., Perlmutter, J.D., Pan, J., Tristram-Nagle, S., Katsaras, J., Sachs, J.N. The effect of cholesterol on short- and long-chain monounsaturated lipid bilayers as determined by molecular dynamics simulations and X-ray scattering. Biophys. J. 2008, 95, 2792-805. 

C Lagerquist, F Beigi, A Karlen, H Lennernas, P Lundahl. Effects of cholesterol and model transmembrane proteins on drug partitioning into lipid bilayers as analyzed by immobilized-liposome chromatography. J Pharm Pharmacol 53 1477-1487, 2001. 

Ghck H, Heyse JE, Thompson D, Epstein RS, Smith ME, Oster G. A model for evaluating the cost-effectiveness of cholesterol-lowering treatment. Int J Technol Assess Health Care 1992 8 719-34. 

J. Forbes, C. Husted and E. Oldfield, High-field, high-resolution magic-angle samplespinning nuclear magnetic resonance spectroscopic studies of gel and liquid crystalline lipid bilayers and the effects of cholesterol, J. Am. Chem. Soc., 1988, 110, 1059-1065. 

The unsaturated phospholipid from soybean lecithin also shows a similar effect, while the unsaturated phospholipids from red blood cell membranes, although showing a slight effect of cholesterol interaction, still show a prominent polymethylene peak in the high resolution spectrum. 

Figure 13. Effects of cholesterol addition on isotherm of originally expanded component...

The second regulatory mechanism involves the degra-dation of HMG-CoA reductase. As stated in chapter 29 the amount of an enzyme in a cell is determined by both its rate of synthesis and its rate of degradation. The rate of degradation of the reductase appears to be modulated by the supply of cholesterol. Thus, when cholesterol is abundant, the rate of enzyme degradation is twice as fast as when there is a limited supply of cholesterol. The effect of cholesterol on enzyme degradation is mediated by the membrane domain of the enzyme. 

In all our linewidth studies the width of the central peak was measured—i.e., the linewidth obeying Equation lib. In Ref. 45 we reported 23Na linewidth studies on a lamellar mesophase containing egg-yolk lecithin. The effect of cholesterol on the linewidth was investigated, and we found that with increasing cholesterol content in the phospholipid bilayers a marked reduction in the linewidth was observed. In accordance with similar investigations for simple soap-alcohol-water lamellar mesophases (42, 43) this is interpreted as a partial release of... 

Handa, T., Eguchi, Y., and Miyajima, K. (1994) Effects of cholesterol and cholesteryl oleate on lipolysis and liver uptake oftriglycerides/phosphatidylcholine emulsions in iBIsarm. Res., 11 1283-1287. 

Cox, D.C., K. Comai, and A.L. Goldstein. 1988. Effects of cholesterol and 25-hydroxycholesterol on smooth muscle cell and endothelial cell growth. Lipids 23 85. 

Motivated by its important role in gene delivery, we have studied the effect of cholesterol (chol) and several analogs on the transfection efficiency of lamellar CL-DNA complexes in vitro [27]. As evident from the results on DOPC/DOTAP and DOPE/DOTAP vectors, the nature of the neutral lipid component is an important parameter that is worth further exploration. Conveniently, a number of neutral lipids are commercially available. In addition, modifying the neutral lipid component has the potential to improve TE in a regime (at low aM) where DNA dissociation from the complex in the cytosol is not yet a barrier to transfection. 

Gylling, H. and Miettinen, T.A. 1995. The effect of cholesterol absorption inhibition on low density lipoprotein cholesterol level. Atherosclerosis 117, 305-308. 

Vuoristo, M. and Miettinen, T.A. 1994. Absorption, metabolism, and serum concentrations of cholesterol in vegetarians Effects of cholesterol feeding. Am. J. Clin. Nutr. 59, 1325-1331. 

Engstrom G, Lind P, Hedblad B, Stavenow L, Janzon L, Lindgarde F. Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of myocardial infarction and stroke in men. Circulation 2002 105 2632-2637. 

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