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

  • Yu-Jin Jeong (a1), Yean-Jung Choi (a1), Hyang-Mi Kwon (a1), Sang-Wook Kang (a1), Hyoung-Sook Park (a2), Myungsook Lee (a3) and Young-Hee Kang (a1)
  • DOI:
  • Published online: 01 March 2007

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.

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*Corresponding author: Dr Young-Hee Kang, fax +82 33 254 1475, email
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M Aviram & B Fuhrman (2002) Wine flavonoids protect against LDL oxidation and atherosclerosis. Ann N Y Acad Sci 957, 146161.

SK Basu , JL Goldstein , RGW Anderson & MS Brown (1976) Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts. Proc Natl Acad Sci USA 73, 31783182.

T Bito , S Roy , CK Sen , T Shirakawa , A Gotoh , M Ueda , M Ichihashi & L Packer (2002) Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS Lett 520, 145152.

TM Buttke & PA Sandstrom (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15, 710.

SM Colles , JM Maxson , SG Carlson & GM Chisholm (2001) Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Trends Cardiovasc Med 11, 131138.

F Denizot & R Lang (1986) Rapid colorimetric assay for cell growth and survival. Modification to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods 89, 271277.

AJ Dugas Jr, J Castaneda-Acosta , GC Bonin , KL Price , NH Fischer , GW Winston (2000) Evaluation of the total peroxyl radical-scavenging capacity of flavonoids: structure–activity relationships. J Nat Prod 63, 327331.

R Freese , S Basu , E Hietanen , J Nair , K Nakachi , H Bartsch & M Mutanen (1999) Green tea extract decreases plasma malondialdehyde concentration but does not affect other indicators of oxidative stress, nitric oxide production, or hemostatic factors during a high-linoleic acid diet in healthy females. Eur J Nutr 38, 149157.

R Funabiki , K Takeshita , Y Miura , M Shibasato & T Nagasawa (1999) Dietary supplement of G-rutin reduces oxidative damage in the rodent model. J Agric Food Chem 47, 10781082.

Y Gavrieli , Y Sherman & SA Ben-Sasson (1992) Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119, 493501.

L Giovannini , M Migliori , BM Longoni , DK Das , AA Bertelli , V Panichi , C Filippi & A Bertelli (2001) Resveratrol, a polyphenol found in wine, reduces ischemia reperfusion injury in rat kidneys. J Cardiovasc Pharmacol 37, 262270.

A Graham , JL Wood , VJ O'Leary & D Stone (1996) Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism. Free Radic Res 25, 181192.

R Gugler , M Leschik & HJ Dengler (1975) Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol 9, 229234.

CC Hsieh , MH Yen , CH Yen & YT Lau (2001) Oxidized low density lipoprotein induces apoptosis via generation of reactive oxygen species in vascular smooth muscle cells. Cardiovasc Res 49, 135145.

RS Hundal , A Gomez-Munoz , JY Kong , BS Salh , A Marotta , V Duronio & UP Steinbrecher (2003) Oxidized low density lipoprotein inhibits macrophage apoptosis by blocking ceramide generation, thereby maintaining protein kinase B activation and Bcl-XL levels. J Biol Chem 278, 2439924408.

EA Jaffe , RL Nachman , CG Becker & CR Minick (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52, 27452756.

YH Kang , SH Park , YJ Lee , JS Kang , IJ Kang , HK Shin , JHY Park & R Bunger (2002) Antioxidant α-keto-carboxylate pyruvate protects low-density lipoprotein and atherogenic macrophages. Free Radic Res 36, 905914.

H Kataoka , N Kume , S Miyamoto , M Minami , M Morimoto , K Hayashida , N Hashimoto & T Kita (2001) Oxidized LDL modulates Bax/Bcl-2 through the lectin like Ox-LDL receptor-1 in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 21, 955960.

PM Kris-Etherton & CL Keen (2002) Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol 13, 4149.

C Manach & JL Donovan (2004) Pharmacokinetics and metabolism of dietary flavonoids in humans. Free Radic Res 38, 771785.

W Martinet & MM Kockx (2001) Apoptosis in atherosclerosis: focus on oxidized lipids and inflammation. Curr Opin Lipidol 12, 535541.

J Milde , EF Elstner & J Grassmann (2004) Synergistic inhibition of low-density lipoprotein oxidation by rutin, γ-terpinene, and ascorbic acid. Phytomedicine 11, 105113.

C Napoli , O Quehenberger , F De Nigris , P Abete , CK Glass & W Palinski (2000) Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells. FASEB J 14, 19962007.

SR Panini & MS Sinensky (2001) Mechanisms of oxysterol-induced apoptosis. Curr Opin Lipidol 12, 529533.

AS Pannala , CA Rice-Evans , B Halliwell & S Singh (1997) Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Biochem Biophys Res Commun 232, 164168.

KL Retsky & B Frei (1995) Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein. Biochim Biophys Acta 1257, 279287.

KL Retsky , K Chen , J Zeind & B Frei (1999) Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper binding to LDL and 2-oxo-histidine formation. Free Radic Biol Med 26, 9098.

CA Rice-Evans , NJ Miller & G Paganga (1996) Structure–antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20, 933956.

R Ross (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801809.

JT Salonen , S Ylä-Hertuala , R Yamamoto , S Butler , H Korpela , R Salonen , K Nyyssonen , W Palinski & JL Witztum (1992) Autoantibody against oxidised LDL and progression of carotid atherosclerosis. Lancet 339, 883887.

R Salvayre , N Auge , H Benoist & A Negre-Salvayre (2002) Oxidized low-density lipoprotein-induced apoptosis. Biochim Biophys Acta 1585, 213221.

L Sartor , E Pezzato , I Dell'aica , R Caniato , S Biggin & S Garbisa (2002) Inhibition of matrix-proteases by flavonoids: chemical insights for anti-inflammatory and anti-invasion drug design. Biochem Pharmacol 64, 229237.

VA Shatrov & B Brune (2003) Induced expression of manganese superoxide dismutase by non-toxic concentrations of oxidized low-density lipoprotein (oxLDL) protects against oxLDL-mediated cytotoxicity. Biochem J 374, 505511.

N Vacaresse , O Vieira , F Robbesyn , G Jürgens , R Salvayre & A Negre-Salvayre (2001) Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL-induced EGF-receptor activation. Br J Pharmacol 132, 17771788.

DW Voehringer & RE Meyn (2000) Redox aspects of bcl-2 function. Antioxid Redox Signal 2, 537550.

JC Voyta , DP Via , CE Butterfield & BR Zetter (1984) Identification and isolation of endothelial cells based on their increased uptake of acetyl-low density lipoprotein. J Cell Biol 99, 20342040.

T Walle (2004) Absorption and metabolism of flavonoids. Free Radic Biol Med 36, 829837.

A Warnholtz , G Nickenig & E Schulz (1999) Increased NADH-oxidase-mediated superoxide production in the early stages of atherosclerosis: evidence for involvement of the renin-angiotensin system. Circulation 99, 20272033.

G Williamson (2002) The use of flavonoid aglycones in in vitro systems to test biological activities: based on bioavailability data, is this a valid approach?. Phytochem Rev 1, 215222.

ES Wintergerst , J Jelk , C Rahner & R Asmis (2000) Apoptosis induced by oxidized low density lipoprotein in human monocyte-derived macrophages involves CD36 and activation of caspase-3. Eur J Biochem 267, 60506059.

AH Wyllie , RG Morris , AL Smith & D Dunlop (1984) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142, 6777.

L Yang & MS Sinensky (2000) 25-Hydroxycholesterol activates a cytochrome c release-mediated caspase cascade. Biochem Biophys Res Commun 278, 557563.

H Zhu , Y Takahashi , W Xu , H Kawajiri , T Murakami , M Yamamoto , S Iseki , T Iwasaki , H Hattori & T Yoshimoto (2003) Low density lipoprotein receptor-related protein-mediated membrane translocation of 12/15-lipoxygenase is required for oxidation of low density lipoprotein by macrophages. J Biol Chem 278, 1335013355.

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