Cholesterol is a major component of cell membrane and plays a key role in maintaining membrane physiological functions and physicochemical properties. Cholesterol is absorbed by gastrointestinal tract and is synthesized by liver. 3–Hydroxy–3–methylglutaryl coenzyme A (HMG–CoA) reductase is a rate–limiting enzyme of mevalonate pathway involving cholesterol biosynthesis. So–called statin, HMG–CoA reductase inhibitor, is available in this country, and is widely applied to the patients with dyslipidemia. In this article, I would like to describe the episode of the discovery of statin in relation to the interaction between the cholesterol content and physiological functions of cell membrane in health and disease.

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Statin inhibits HMG CoA reductase in cholesterol biosynthesis and lowers cholesterol levels in blood. It has been established by a lot of clinical studies that statin has protective effects against cardiovascular diseases. Experimental studies have shown that statin inhibits membrane translocation of Rho and Ras GTPases that results in activation, by decreasing cellular levels of isoprenoid intermediates. Inhibition of Rho by statin increases VEGF expression in endothelial cells that promotes cell survival. Statin also prevents endothelial hyperpermeability that is implicated in atherogenesis. Ras-mediated activation of T type calcium channel that may result in endothelial cell dysfunction is blocked by statin. Accordingly, statin has pleiotropic effects on cardiovascular cell function by modulating cell signaling.

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HMG CoA reductase inhibitor or statin has been used for dyslipidemia for more than 10 years. Numerous clinical studies proved that it significantly reduces incidence of coronary heart diseases. The inhibition of HMG CoA reductase reduces de novo cholesterol production and also reduces the production of small GTP binding protein such as RhoA and RAS. Since biomembrane consists of huge amount of cholesterol, statin may also influence the membrane fluidity and thus signaling functions. Therefore intracellular signaling can be modulated by statin through cholesterol– dependent and –independent pathway.

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Systems of subgenomic replicon and recombinant infectious hepatitis C virus (HCV) have been established in 1999 and 2005, and virological techniques are able to be applied to the HCV research, especially regarding molecular mechanisms on replication and virion assembly, respectively. We showed that HCV active replication complex contains membrane structures, characteristic of lipid rafts. We also recently demonstrated an important role of cholesterol and sphingolipid in HCV infection and virion maturation. Finally, inhibitors of cellular cholesterol and sphingolipid biosynthetic pathway efficiently block virion production. Association of hepatitis C virus with lipid can be also a source of new antiviral therapies.

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Osteoporosis is the disease in the condition that the activity of the osteoclast surpasses that of the osteoblast. A variety of endocrine hormones, such as PTH play the important roles in the bone remodeling. Recently, several kinds of evidence including basic science and clinical studies show that the stain has the positive effect on bone formation. Therefore, in this review, we show the studies about the mechanism how the statin works on the osteoblast using the chondrocyte cell line; ATDC5 cells, and mouse tibia organ culture. Furthermore, the series of recent metaanalysis of the statin and osteoporosis are discussed.

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Immobilized liposome membrane (ILM) was prepared in hollow fiber module (HF–ILM), where the liposome was loaded into the hollow fiber membrane module and was physically immobilized by forming the hydrogel in the cavity of the fiber membrane. Basic nature of the hydrogels prepared with xanthan gum (XG) and polyethyleneimine (PEI) via amino coupling method was first investigated in relation to the water contents of the gel matrix, so that the optimal condition for the liposome immobilization was obtained. The HF–ILM was prepared at the optimal condition, resulting in the high contents of immobilized liposome with high stability.

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Photo–cured DNA–4–vinylbenzyltrimethylammonium (DNA–VBTMA) complex membranes were obtained by UV curing of DNA–4–vinylbenzyltrimethylammonium complex membranes and photoinitiator, 2–hydroxy–2–methyl–1– phenyl–1–propanone (HMPP). The membrane with arbitrary charged state was obtained by adjusting the feed composition in membrane preparation process. The positively and negatively charged membranes showed optical resolution ability; in other words, those two types of membrane transported D–Lys in preference to L–Lys from racemic mixture of Lys. The permselectivity toward D–Lys reached 1.52. The membranes showing chiral separation ability selectively incorporated the D–isomer of Lys into them. In the present study, the permselectivity was mainly expressed by the affinity between D–Lys and membranes.

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We introduced a new EDI (Electro Deionization) system into a conventional type of RO system for the purification of the dialysate water. The EDI stack consists of a dialyzer where a cation exchange membrane and an anion exchange membrane were alternately arranged, and an ion exchange resin was filled between the membranes. Electric conductivity of the RO water decreased from 3.85 μS/cm to 0.07 μS/cm after the treatment of EDI, and silica and aluminum with a difficult removal by a conventional RO system were removed by the EDI system. Furthermore, endotoxin can be highly removed, and the rejection of the endtoxin was increased with the current. The EDI system was available for the purification of the dialysate water.

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