Cholesterol Research Today is a free monthly online journal that collates and summarizes the latest research about Cholesterol, including details on high cholesterol, hdl, ldl, diet, risks.

Cholesterol biosynthesis modulation regulates dengue viral replication.

Rothwell C, Lebreton A, Young Ng C, Lim JY, Liu W, Vasudevan S, Labow M, Gu F, Gaither LA

Novartis Institutes for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA.

We performed a focused siRNA screen in an A549 dengue type 2 New Guinea C subgenomic replicon cell line (Rluc-replicon) that contains a Renilla luciferase cassette. We found that siRNA mediated knock down of mevalonate diphospho decarboxylase (MVD) inhibited viral replication of the Rluc-replicon and DEN-2 NGC live virus replication in A549 cells. When the Rluc-replicon A459 cells were grown in delipidated media the replicon expression was suppressed and MVD knock down could further sensitize Renilla expression. Hymeglusin and zaragozic acid A could inhibit DEN-2 NGC live virus replication in K562 cells, while lovastatin could inhibit DEN-2 NGC live virus replication in human peripheral blood mononuclear cells. Renilla expression could be rescued in fluvastatin treated A549 Rluc-replicon cells after the addition of mevalonate, and partially restored with geranylgeranyl pyrophosphate, or farnesyl pyrophosphate. Our data suggest genetic and pharmacological modulation of cholesterol biosynthesis can regulate dengue virus replication.

Published 9 June 2009 in Virology, 389(1): 8-19.
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Articles on Cholesterol published 28 May 2009:

Interleukin-18 predicts atherosclerosis progression in SIV-infected and uninfected rhesus monkeys (Macaca mulatta) on a high-fat/high-cholesterol diet.   Lab Invest, 89(6): 657-67.

Interleukin (IL)-18 levels have been identified as important predictors of cardiovascular mortality and are often elevated in human immunodeficiency virus (HIV)-infected individuals. To investigate a possible function for IL-18 in atherogenesis in the context of early HIV infection, we used the simian immunodeficiency model of HIV infection. Acutely simian immunodeficiency virus-infected and uninfected rhesus monkeys (Macaca mulatta) on an atherogenic diet were evaluated prospectively for ... [Abstract] [Full-text]

Articles on Cholesterol published 27 May 2009:

Glycine transporter 1 associates with cholesterol-rich membrane raft microdomains.   Biochem Biophys Res Commun, 384(4): 530-4.

Membrane rafts, the highly-ordered, cholesterol-rich microdomains of the plasma membrane play important roles in cellular functions. In this study, GLYT1-CFP and GLYT2-CFP were constructed, followed by investigation of whether the tagged transporters associate with a fluorescence probe that labels membrane rafts (DilC16) by using Fluorescence Resonance Energy Transfer. A close association was observed between DiIC16 and GLYT1-CFP, but not for GLYT2-CFP. The glycine transport ability of GLYT1 is ... [Abstract] [Full-text]

Chemical inhibition of alpha-toxin, a key corneal virulence factor of Staphylococcus aureus.   Invest Ophthalmol Vis Sci, 50(6): 2848-54.

PURPOSE: alpha-Toxin mediates extreme corneal damage during Staphylococcus aureus keratitis. Chemical inhibition of this toxin was sought to provide relief from toxin-mediated pathology. METHODS: Inhibition of alpha-toxin by phosphate-buffered saline (PBS), 0.1% methyl-beta-cyclodextrin (CD), or CD plus cholesterol (0.1%, CD-cholesterol) was assayed by hemolysis of rabbit erythrocytes. Pathologic changes in rabbit corneas injected with 12 hemolytic units of alpha-toxin suspended in PBS, 1% CD, ... [Abstract] [Full-text]

Articles on Cholesterol published 25 May 2009:

Effect on serum lipid levels of switching dose of ezetimibe from 10 to 5 mg.   Am J Cardiol, 103(11): 1568-71.

Although during its initial development, lower doses of ezetimibe reduced low-density lipoprotein (LDL) significantly, ezetimibe is available only in 10-mg form. Compliant patients receiving ezetimibe 10 mg were randomized in a blinded fashion to continue therapy with ezetimibe 10 mg or to convert to a split-tablet 5-mg dose. Lipid panels were collected at baseline and after 4 weeks of therapy. The impact of the 2 ezetimibe dosing strategies on LDL and the achievement of the Adult Treatment ... [Abstract] [Full-text]

Articles on Cholesterol published 22 May 2009:

Statin-induced liver injury involves cross-talk between cholesterol and selenoprotein biosynthetic pathways.   Mol Pharmacol, 75(6): 1421-9.

Statins have become the mainstay of hypercholesterolemia treatment. Despite a seemingly clear rationale behind their use, the inhibition of HMG-CoA reductase, these compounds have been shown to elicit a variety of unanticipated and elusive effects and side effects in vivo. Among the most frequently noted side effects of statin treatment are elevations in liver enzymes. Here, we report our finding that atorvastatin, cerivastatin, and lovastatin at clinically common concentrations induce a ... [Abstract] [Full-text]

Articles on Cholesterol published 21 May 2009:

HDL-cholesterol, blood pressure, and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children.   Arterioscler Thromb Vasc Biol, 29(6): 943-9.

OBJECTIVE: Atherosclerosis is found at autopsy in the arteries of adolescents and young adults. Arterial wall thickening may be assessed in vivo by ultrasound measurement of the carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis. As the determinants of arterial wall thickness in childhood are unknown, we assessed the influence of cardiovascular risk factors on CIMT in 8-year-old children. METHODS AND RESULTS: A community-based sample of 405 children (age 8.0+/-0.1 ... [Abstract] [Full-text]

Overexpression of human 15(S)-lipoxygenase-1 in RAW macrophages leads to increased cholesterol mobilization and reverse cholesterol transport.   Arterioscler Thromb Vasc Biol, 29(6): 837-42.

OBJECTIVE: The purpose of this study was to determine the effect of 15-lipoxygenase-1 (15-LO-1) on cholesterol mobilization from macrophages. METHODS AND RESULTS: Overexpression of human 15-LO-1 in RAW mouse macrophages led to enhanced cholesterol efflux, increased cholesteryl ester (CE) hydrolysis, and increased reverse cholesterol transport (RCT). Efflux studies comparing 15-LO-1 overexpressing cells to mock-transfected RAW macrophages resulted in a 3- to 7-fold increase in cholesterol efflux ... [Abstract] [Full-text]

Relationships of HDL cholesterol, ApoA-I, and ApoA-II with homocysteine and creatinine in patients with type 2 diabetes treated with fenofibrate.   Arterioscler Thromb Vasc Biol, 29(6): 950-5.

OBJECTIVE: The purpose of this study was to determine fenofibrate-induced changes in plasma high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) A-I, and apolipoprotein (apo) A-II and how they relate to changes in plasma homocysteine and creatinine. METHODS AND RESULTS: FIELD was a double-blind placebo-controlled trial done in Australia, New Zealand, and Finland. All FIELD subjects were included except those who started statin therapy or permanently discontinued fenofibrate. ... [Abstract] [Full-text]

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