Comparison of the apoptotic processes induced by the oxysterols 7beta-hydroxycholesterol and cholesterol-5beta,6beta-epoxide.
Oxysterols have been shown to induce apoptosis in a variety of cell lines. The mechanism of oxysterol-induced apoptosis is mainly known at the post-mitochondrial level. The aim of the present study was to compare the pathway of apoptosis induced by the oxysterols 7beta-hydroxycholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide) in U937 cells. To this end, we employed a range of inhibitors of apoptosis; a broad-spectrum caspase inhibitor, a specific caspase-3 inhibitor and an inhibitor of cytochrome c release and the antioxidants; trolox, ebselen and resveratrol. The three inhibitors of apoptosis prevented cell death induced by 7beta-OH; however, in beta-epoxide-treated cells, the inhibitor of cytochrome c release did not protect against apoptosis. The cellular antioxidant glutathione was depleted in 7beta-OH-treated cells but not in cells incubated with beta-epoxide. Trolox, a water-soluble synthetic analogue of alpha-tocopherol, prevented 7beta-OH-induced apoptosis but did not protect against cell death induced by beta-epoxide. Ebselen and resveratrol did not protect U937 cells against apoptosis induced by either 7beta-OH or beta-epoxide. Our results suggest that differences occur in the pathways of apoptosis induced by 7beta-OH and beta-epoxide in U937 cells.
Ryan
L
L
Department of Food and Nutritional Sciences, University College Cork, Ireland.
O'Callaghan
Y C
YC
O'Brien
N M
NM
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006888:Hydroxycholesterols / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology
D006888:Hydroxycholesterols; C002415:cholesterol alpha-oxide; D002784:Cholesterol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione