Modulation by α- and γ-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human corollary smooth muscle cells
Modulation by α- and γ-tocopherol and oxidized low-density lipoprotein of apoptotic signaling in human corollary smooth muscle cells
复制标题
DOI：
10.1016/s0006-2952(00)00275-6
复制
发表时间：
2000-06-01
影响因子：
5.8
通讯作者：
Napoli, C
中科院分区：
文献类型：
--
作者：
de Nigris, F;Franconi, F;Napoli, C
细胞凋亡可能在动脉粥样硬化的形成中起重要作用。氧化低密度脂蛋白（oxLDL）除了具有其他致动脉粥样硬化作用外，还可促进动脉粥样硬化中的细胞凋亡。在流行病学研究中，生育酚补充剂被认为可以预防冠心病（CHD）。氧化低密度脂蛋白和α-和γ-生育酚对细胞凋亡信号通路的影响知之甚少。因此，本研究的目的是在人冠状动脉平滑肌细胞（SMC）中研究铜氧化LDL和生育酚存在下的这些途径。我们发现，oxLDL介导的细胞凋亡，DNA片段化，末端脱氧核苷酸转移酶（TdT）介导的dUTP缺口末端标记（TUNEL）测定，和caspase激活刺激几个转录因子和促凋亡的动态运动的Bcl-2家族蛋白通过丝裂原活化蛋白激酶（MAPK）和Jun激酶途径。α-生育酚和γ-生育酚显著降低这些分子事件和细胞死亡效应物半胱天冬酶-3和-8。在我们的实验条件下，α-生育酚比γ-生育酚明显更有效，oxLDL介导的细胞凋亡增加了c-Jun，环AMP反应元件结合，Ets样元件激酶依赖性7和激活转录因子-2蛋白以及人冠状动脉SMC中活化蛋白-1复合物的核活性。此外，我们的研究结果表明，生育酚可以发挥其抗动脉粥样硬化的作用，至少部分通过减少MAPK和JunK级联连同Bcl-2家族的凋亡基因的保护性配置文件。这些数据与实验研究中观察到的生育酚对动脉粥样硬化形成和流行病学调查中对CHD的有益作用一致。生物化学制药59; 11：1477 - 1487，2000年。(C)2000 Elsevier Science Inc.
Apoptosis may play an important role in atherogenesis. Oxidized low-density lipoprotein (oxLDL) promotes apoptosis in the arterial a all in addition to several other proatherogenic effects. Tocopherol supplements have been suggested to protect against coronary heart disease (CHD) in epidemiological studies. The effects of oxLDL and alpha- and gamma-tocopherol on apoptotic signaling pathways are poorly understood. Thus, the goal of the study was to investigate these pathways in the presence of copper-oxidized LDL and tocopherols in human coronary smooth muscle cells (SMC). We showed that oxLDL-mediated apoptosis, assessed by DNA fragmentation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, and caspase activation stimulated several transcription factors and proapoptotic dynamic movements of the Bcl-2 family proteins through the mitogen-activated protein kinase (MAPK) and Jun kinase pathways. alpha-Tocopherol and gamma-tocopherol significantly reduced these molecular events and cell death effectors caspase-3 and -8. Under our experimental conditions, alpha-tocopherol was significantly more effective than gamma-tocopherol, and oxLDL-mediated apoptosis increased c-Jun, cyclic AMP-responsive element-binding, Ets-like element kinase dependent 7, and activating transcription factor-2 proteins as well as nuclear activity of the activated protein-1 complex in human coronary SMC. Moreover, our results demonstrate that tocopherols may exert their antiatherogenic effects at least in part via reduction of the MAPK and JunK cascade together with a protective profile of apoptotic genes of the Bcl-2 family. These data are consistent with the beneficial effects of tocopherols on atherogenesis seen in experimental studies and on CHD in epidemiological surveys. BIOCHEM PHARMACOL 59;11:1477-1487, 2000. (C) 2000 Elsevier Science Inc.