Peer-Reviewed Journal Details
Mandatory Fields
Ryan, L;O'Callaghan, YC;O'Brien, NM
2005
October
British Journal of Nutrition
The role of the mitochondria in apoptosis induced by 7 beta-hydroxycholesterol and cholesterol-5 beta,6 beta-epoxide
Validated
WOS: 43 ()
Optional Fields
PERMEABILITY TRANSITION PORE LOW-DENSITY-LIPOPROTEIN CELL-DEATH OXIDIZED LDL 7-KETOCHOLESTEROL-INDUCED APOPTOSIS ENDOTHELIAL-CELLS OXIDATIVE STRESS HEPG2 CELLS CHOLESTEROL ETOPOSIDE
94
519
525
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 7 beta-hydroxycholesterol (7 beta-OH) and cholesterol-5 beta,6 beta-epoxide (beta-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. 7 beta-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 7 beta-OH-induced cell death. In contrast, beta-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 7 beta-OH-induced apoptosis occurs via the mitochondrial pathway and highlights differences in the apoptotic pathways induced by 7 beta-OH and beta-epoxide in U937 cells.
WALLINGFORD
0007-1145
10.1079/BJN20051524
Grant Details