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In vitro folate supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-ketocholesterol

Published online by Cambridge University Press:  09 March 2007

R.-F. S. Huang ,
H.-C. Yaong ,
S.-C. Chen  and
Y.-F. Lu
R.-F. S. Huang*
Affiliation:
Department of Nutrition and Food Sciences, Fu-Jen University, Hsin-Chuang, Taiwan, Republic of China
H.-C. Yaong
Affiliation:
Department of Nutrition and Food Sciences, Fu-Jen University, Hsin-Chuang, Taiwan, Republic of China
S.-C. Chen
Affiliation:
Department of Nutrition and Food Sciences, Fu-Jen University, Hsin-Chuang, Taiwan, Republic of China
Y.-F. Lu
Affiliation:
Department of Nutrition and Food Sciences, Fu-Jen University, Hsin-Chuang, Taiwan, Republic of China
*
*Corresponding author: Dr R.-F. S. Huang, fax +86 2 29021215, email, rweifen@mails.fju.edu.tw
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Abstract

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Folate has recently been proposed as a new antioxidant. Folate supplementation may have a protective effect in counteracting oxidant-induced apoptotic damage. The present studies were undertaken to examine whether there is a direct link between folate levels, antioxidant capability and reduced apoptotic damage. Using an in vitro cellular model of 7-ketocholesterol (KC)-induced apoptosis, U937 cells were pre-cultured with a folate-deficient medium supplemented with various levels of folate (2–1500μmol/l) before treatment with 7-KC. Apoptotic markers, mitochondria-associated death signals and levels of reactive oxygen species were assayed. After treatment with 7-KC for 30h, low and high levels of folate supplementation significantly (P<0.05) reduced nuclear DNA loss. Only high levels of folate supplementation (>1000μmol/l) were effective in counteracting 7-KC-promoted apoptotic membrane phosphatidylserine exposure and DNA laddering. The attenuation of 7-KC-induced apoptotic damage by high-dose folate supplementation coincided with a partial normalization of mitochondria membrane potential dissipation, a suppression of cytochrome c release and an inhibition of procaspase 3 activation. The prevention of mitochondrial dysfunctions and apoptotic processes was associated with antioxidant actions of high-dose folate by a marked scavenging of intracellular superoxide. Collectively, our present results demonstrate that in vitro folate supplementation exerts differentially protective effects against 7-KC-induced damage. High-dose supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-KC. However, the in vivo relevance is not clear and requires further study.

Keywords

Folate supplementationAntioxidantApoptosisMitochondria-associated death signalling7-Ketocholesterol
Type
Review Article
Information
British Journal of Nutrition , Volume 92 , Issue 6 , December 2004 , pp. 887 - 894
Copyright
Copyright © The Nutrition Society 2004

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