Comparison of the apoptotic processes induced by the oxysterols 7β-hydroxycholesterol and cholesterol-5β,6β-epoxide |
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Authors: | L Ryan YC O’Callaghan NM O’Brien |
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Institution: | (1) Department of Food and Nutritional Sciences, University College Cork, Ireland |
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Abstract: | 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 7-hydroxycholesterol (7-OH) and cholesterol-5,6-epoxide (-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 cytochromec release and the antioxidants; trolox, ebselen and resveratrol. The three inhibitors of apoptosis prevented cell death induced by 7-OH; however, in -epoxide-treated cells, the inhibitor of cytochromec release did not protect against apoptosis. The cellular antioxidant glutathione was depleted in 7-OH-treated cells but not in cells incubated with -epoxide. Trolox, a water-soluble synthetic analogue of -tocopherol, prevented 7-OH-induced apoptosis but did not protect against cell death induced by -epoxide. Ebselen and resveratrol did not protect U937 cells against apoptosis induced by either 7-OH or -epoxide. Our results suggest that differences occur in the pathways of apoptosis induced by 7-OH and -epoxide in U937 cells. |
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Keywords: | antioxidants apoptosis cholesterol-5" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0"> 6-epoxide" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0">-epoxide 7-hydroxycholesterol" target="_blank">gif" alt="beta" align="MIDDLE" BORDER="0">-hydroxycholesterol U937 cells |
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