Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages

High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction w...

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Main Authors: Dana Atrahimovich, Soliman Khatib, Shifra Sela, Jacob Vaya, Abraham O. Samson
Format: Article
Language:English
Published: Hindawi Limited 2016-01-01
Series:Oxidative Medicine and Cellular Longevity
Online Access:http://dx.doi.org/10.1155/2016/7124251
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spelling doaj-e9fecc53e6934daaafebf00cb9a7ffb62020-11-24T23:05:57ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942016-01-01201610.1155/2016/71242517124251Punicalagin Induces Serum Low-Density Lipoprotein Influx to MacrophagesDana Atrahimovich0Soliman Khatib1Shifra Sela2Jacob Vaya3Abraham O. Samson4Department of Oxidative Stress and Human Diseases, MIGAL–Galilee Research Institute, 11016 Kiryat Shmona, IsraelDepartment of Oxidative Stress and Human Diseases, MIGAL–Galilee Research Institute, 11016 Kiryat Shmona, IsraelFaculty of Medicine in the Galilee, Bar-Ilan University, 1311502 Safed, IsraelDepartment of Oxidative Stress and Human Diseases, MIGAL–Galilee Research Institute, 11016 Kiryat Shmona, IsraelFaculty of Medicine in the Galilee, Bar-Ilan University, 1311502 Safed, IsraelHigh levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.http://dx.doi.org/10.1155/2016/7124251
collection DOAJ
language English
format Article
sources DOAJ
author Dana Atrahimovich
Soliman Khatib
Shifra Sela
Jacob Vaya
Abraham O. Samson
spellingShingle Dana Atrahimovich
Soliman Khatib
Shifra Sela
Jacob Vaya
Abraham O. Samson
Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
Oxidative Medicine and Cellular Longevity
author_facet Dana Atrahimovich
Soliman Khatib
Shifra Sela
Jacob Vaya
Abraham O. Samson
author_sort Dana Atrahimovich
title Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
title_short Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
title_full Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
title_fullStr Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
title_full_unstemmed Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages
title_sort punicalagin induces serum low-density lipoprotein influx to macrophages
publisher Hindawi Limited
series Oxidative Medicine and Cellular Longevity
issn 1942-0900
1942-0994
publishDate 2016-01-01
description High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL. Punicalagin bound to ApoB100 at low concentrations (0.25–4 μM). Upon binding, it induced LDL influx to macrophages in a concentration-dependent manner, up to 2.5-fold. In contrast, another polyphenol which binds to ApoB100, glabridin, did not affect LDL influx. We further showed that LDL influx occurs specifically through the LDL receptor, with LDL then accumulating in the cell cytoplasm. Taken together with the findings of Aviram et al., 2000, that pomegranate juice and punicalagin induce plasma LDL removal and inhibit macrophage cholesterol synthesis and accumulation, our results suggest that, upon binding, punicalagin stimulates LDL influx to macrophages, thus reducing circulating cholesterol levels.
url http://dx.doi.org/10.1155/2016/7124251
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