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The potentiation of ox-LDL induced apoptosis by inhibition of NF-kappa B

机译:ox-LDL通过抑制NF-κB增强细胞凋亡

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摘要

We previously reported that oxidized low density lipoprotein (ox-LDL) induced apoptosis in vascular smooth muscle cells (VSMCs). However, the transcription factors important for apoptotic signalling have been little clarified. We investigated the involvement of nuclear factor-kappa B (NF-kappa B), by which apoptotic signalling is reported to be mediated, in ox-LDL-induced apoptosis. The effect of ox-LDL on the transcriptional factor NF-kappa B activation was investigated by electrophoretic mobility shift assay (EMSA), Ox-LDL caused NF-kappa B activation in VSMCs. Next, we investigated the effect on ox-LDL-induced apoptosis by introduction of synthetic double-stranded DNA with high affinity for NF kappa B in vitro as "decoy" cis elements that bind the transcriptional factor. Treatment by transfection of NF-kappa B decoy oligodeoxynucleotides (ODN), but not scramble ones, blunted the activation of NF-kappa B by ox-LDL and caused a significant further induction of ox-LDL-induced apoptosis. Results indicate that the activation of NF-kappa B prevents excessive apoptosis by ox-LDL in VSMCs. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 23]
机译:我们以前曾报道过氧化的低密度脂蛋白(ox-LDL)诱导血管平滑肌细胞(VSMCs)凋亡。然而,对于凋亡信号转导重要的转录因子几乎没有被阐明。我们调查了核因子-κB(NF-κB)在ox-LDL诱导的细胞凋亡中的参与,据报道该因子通过凋亡信号介导。通过电泳迁移率迁移分析(EMSA)研究了ox-LDL对转录因子NF-κB活化的影响,Ox-LDL在VSMC中引起了NF-κB活化。接下来,我们通过引入对NFκB具有高亲和力的合成双链DNA作为结合转录因子的“诱饵”顺式元件,研究了对ox-LDL诱导的细胞凋亡的影响。通过转染NF-κB诱饵寡聚脱氧核苷酸(ODN)而不是加扰的方法处理,使ox-LDL抑制了NF-κB的活化,并导致进一步明显诱导ox-LDL诱导的细胞凋亡。结果表明,NF-κB的激活可防止ox-LDL在VSMC中过度凋亡。 (C)2000 Elsevier Science Inc.保留所有权利。 [参考:23]

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