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Differential inhibition of oxidized LDL-induced apoptosis in human endothelial cells treated with different flavonoids

Published online by Cambridge University Press:  08 March 2007

Yu-Jin Jeong ,
Yean-Jung Choi ,
Hyang-Mi Kwon ,
Sang-Wook Kang ,
Hyoung-Sook Park ,
Myungsook Lee  and
Young-Hee Kang
Yu-Jin Jeong
Affiliation:
Division of Life Sciences, Hallym University, Chuncheon, South Korea
Yean-Jung Choi
Affiliation:
Division of Life Sciences, Hallym University, Chuncheon, South Korea
Hyang-Mi Kwon
Affiliation:
Division of Life Sciences, Hallym University, Chuncheon, South Korea
Sang-Wook Kang
Affiliation:
Division of Life Sciences, Hallym University, Chuncheon, South Korea
Hyoung-Sook Park
Affiliation:
Department of Environmental Engineering, Hanseo University, South Korea
Myungsook Lee
Affiliation:
Department of Food and Nutrition, Sungshin Women's University, Seoul, Republic of, Korea
Young-Hee Kang*
Affiliation:
Division of Life Sciences, Hallym University, Chuncheon, South Korea
*
*Corresponding author: Dr Young-Hee Kang, fax +82 33 254 1475, email [email protected]
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Abstract

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High plasma level of cholesterol is a well-known risk factor for atherosclerotic diseases. Oxidized LDL induces cellular and nuclear damage that leads to apoptotic cell death. We tested the hypothesis that flavonoids may function as antioxidants with regard to LDL incubated with 5 μm-Cu2+ alone or in combination with human umbilical vein endothelial cells (HUVEC). Cytotoxicity and formation of thiobarbituric acid-reactive substances induced by Cu2+-oxidized LDL were examined in the presence of various subtypes of flavonoid. Flavanols, flavonols and flavanones at a non-toxic dose of 50 μm markedly inhibited LDL oxidation by inhibiting the formation of peroxidative products. In contrast, the flavones luteolin and apigenin had no such effect, with >30 % of cells killed after exposure to 0.1 mg LDL/ml. Protective flavonoids, especially (−)-epigallocatechin gallate, quercetin, rutin and hesperetin, inhibited HUVEC nuclear condensation and fragmentation induced by Cu2+-oxidized LDL. In addition, immunochemical staining and Western blot analysis revealed that anti-apoptotic Bcl-2 expression was enhanced following treatment with these protective flavonoids. However, Bax expression and caspase-3 cleavage stimulated by 18 h incubation with oxidized LDL were reduced following treatment with these protective flavonoids. The down-regulation of Bcl-2 and up-regulation of caspase-3 activation were reversed by the cytoprotective flavonoids, (−)-epigallocatechin gallate, quercetin and hesperetin, at ≥10 μm. These results suggest that flavonoids may differentially prevent Cu2+-oxidized LDL-induced apoptosis and promote cell survival as potent antioxidants. Survival potentials of certain flavonoids against cytotoxic oxidized LDL appeared to stem from their disparate chemical structure. Furthermore, dietary flavonoids may have therapeutic potential for protecting the endothelium from oxidative stress and oxidized LDL-triggered atherogenesis.

Keywords

FlavonoidsEndothelial apoptosisOxidized LDLLipid peroxidationCaspase-3
Type
Research Article
Information
British Journal of Nutrition , Volume 93 , Issue 5 , May 2005 , pp. 581 - 591
Copyright
Copyright © The Nutrition Society 2005

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