کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2201428 | 1100018 | 2011 | 8 صفحه PDF | دانلود رایگان |

Cholesterol oxidation products formed under the enhanced oxidative stress in the brain are suggested to induce neuronal cell death. However, it is still unknown whether oxysterol-induced apoptosis in neuronal cells is mediated by Akt and NF-κB pathways. We assessed the apoptotic effect of 7-ketocholesterol against differentiated PC12 cells in relation to activation of the reactive oxygen species-dependent nuclear factor (NF)-κB, which is mediated by the Akt pathway. 7-Ketocholesterol induced a decrease in cytosolic Bid and Bcl-2 levels, increase in cytosolic Bax levels, cytochrome c release, caspase-3 activation and upregulation of p53. 7-Ketocholesterol induced an increase in phosphorylated inhibitory κB-α, NF-κB p65 and NF-κB p50 levels, binding of NF-κB p65 to DNA, and activation of Akt. Treatment with Bay 11-7085 (an inhibitor of NF-κB activation) and oxidant scavengers, including N-acetylcysteine, prevented the 7-ketocholesterol-induced formation of reactive oxygen species, activation of NF-κB, Akt and apoptosis-related proteins, and cell death. Results from this study suggest that 7-ketocholesterol may exert an apoptotic effect against PC12 cells by inducing activation of the caspase-8-dependent pathway as well as activation of the mitochondria-mediated cell death pathway, leading to activation of caspases, via the reactive oxygen species-dependent activation of NF-κB, which is mediated by the Akt pathway.
Research highlights▶ 7-Ketocholesterol (7-KC), a cholesterol oxidation product, induces apoptosis in differentiated PC12 cells. ▶ 7-KC induces apoptosis via activation of the caspase-8-dependent pathway and the mitochondria-mediated cell death pathway. ▶ 7-KC increases reactive oxygen species formation. ▶ 7-KC induces activation of Akt and NF-κB pathways. ▶ Apoptosis may be mediated by reactive oxygen species-dependent activation of Akt and NF-κB pathways.
Journal: Neurochemistry International - Volume 58, Issue 1, January 2011, Pages 52–59