Lycopene regulation of cholesterol synthesis and efflux in human macrophages |
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Authors: | Palozza Paola Simone Rossella Catalano Assunta Parrone Nadia Monego Giovanni Ranelletti Franco O |
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Affiliation: | aInstitute of General Pathology, Catholic University School of Medicine, 00168 Rome, Italy;bInstitute of Anatomy, Catholic University School of Medicine, 00168 Rome, Italy;cInstitute of Histology, Catholic University School of Medicine, 00168 Rome, Italy |
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Abstract: | Hypercholesterolemia is one of the most important risk factors for atherosclerosis, and tomato lycopene has been suggested to have beneficial effects against such a disease, although the exact molecular mechanism is unknown. We tested the hypothesis that lycopene may exert its antiatherogenic role through changes in cholesterol metabolism. Incubation of THP-1 cells with lycopene (0.5–2 μM) dose-dependently reduced intracellular total cholesterol. Such an effect was associated with a decrease in reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase expression and with an increase in ABCA1 and caveolin-1 (cav-1) expressions. In addition, lycopene enhanced RhoA levels in the cytosolic fraction, activating peroxisome proliferator-activated receptor gamma (PPARγ) and liver X receptor alpha expressions. Concomitant addition of lycopene and the PPARγ inhibitor GW9662 or lycopene and mevalonate blocked the carotenoid-induced increase in ABCA1 and cav-1 expressions. These results imply a potential role of lycopene in attenuating foam cell formation and, therefore, in preventing atherosclerosis by a cascade mechanism involving inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase, RhoA inactivation and subsequent increase in PPARγ and liver X receptor alpha activities and enhancement of ABCA1 and cav-1 expressions. |
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Keywords: | Abbreviations: ABC, ATP-binding cassette cav-1, caveolin-1 GGPP, geranylgeranyl pyrophosphate HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A LXR, liver X receptor PMA, phorbol 22-myristate 13-acetate PPAR, peroxisome proliferator-activated receptor THF, tetrahydrofuran |
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