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The role of the mitochondria in apoptosis induced by 7β-hydroxycholesterol and cholesterol-5β,6β-epoxide

Published online by Cambridge University Press:  08 March 2007

Lisa Ryan
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
Yvonne C. O'Callaghan
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
Nora M. O'Brien*
Affiliation:
Department of Food and Nutritional Sciences, University College Cork, Republic of Ireland
*
*Corresponding author: Dr Nora M. O'Brien, fax +353 21 4270244, email nob@ucc.ie
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Abstract

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Oxysterols are oxygenated derivatives of cholesterol that may be formed endogenously or absorbed from the diet. Significant amounts of oxysterols have frequently been identified in foods of animal origin, in particular highly processed foods. To date, oxysterols have been shown to possess diverse biological activities; however, recent attention has focused on their potential role in the development of atherosclerosis. Oxysterols have been reported to induce apoptosis in cells of the arterial wall, a primary process in the development of atheroma. The aim of the present study was to identify the role of the mitochondria in the apoptotic pathways induced by the oxysterols 7β-hydroxycholesterol (7β-OH) and cholesterol-5β,6β-epoxide (β-epoxide) in U937 cells. To this end, we investigated the effects of these oxysterols on mitochondrial membrane potential, caspase-8 activity, the mitochondrial permeability transition pore and cytochrome c release. 7β-OH-induced apoptosis was associated with a loss in mitochondrial membrane potential after 2 h, accompanied by cytochrome c release from the mitochondria into the cytosol after 16 h. Pre-treatment with a range of inhibitors of the mitochondrial permeability transition pore protected against 7β-OH-induced cell death. In contrast, β-epoxide induced a slight increase in caspase-8 activity but had no effect on mitochondrial membrane potential or cytochrome c release. The present results confirm that 7β-OH-induced apoptosis occurs via the mitochondrial pathway and highlights differences in the apoptotic pathways induced by 7β-OH and β-epoxide in U937 cells.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

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