TRB3, upregulated by ox-LDL, mediates human monocyte-derived macrophage apoptosis
TRB3, upregulated by ox-LDL, mediates human monocyte-derived macrophage apoptosis
复制标题
TRB3 受 ox-LDL 上调，介导人单核细胞源性巨噬细胞凋亡。
DOI：
10.1111/j.1742-4658.2009.06998.x
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发表时间：
2009-05-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Wei
中科院分区：
文献类型：
--
作者：
Shang, Yuan-yuan;Wang, Zhi-hao;Zhang, Wei
Tribble3 (TRB3) 是果蝇 tribbles 的哺乳动物同源物，可减缓细胞周期进程，并且其表达会因各种应激而增加。本研究的目的是探讨TRB3基因在氧化低密度脂蛋白（ox-LDL）诱导的巨噬细胞凋亡中的作用。我们发现，在人单核细胞来源的巨噬细胞中，TRB3 被 ox-LDL 以剂量和时间依赖性方式上调。 TRB3过表达巨噬细胞的细胞活力下降，但细胞凋亡增加，活化的caspase-3水平增加。因子分析显示 TRB3 过表达和 ox-LDL 刺激之间对于巨噬细胞凋亡没有显着的相互作用。此外，TRB3沉默的巨噬细胞显示细胞凋亡减少，而用ox-LDL处理的TRB3沉默的细胞显示细胞凋亡显着增加。 TRB3 沉默和 ox-LDL 刺激对巨噬细胞凋亡显示出显着的相互作用，表明 TRB3 敲低可抵抗 ox-LDL 诱导的巨噬细胞凋亡。因此，TRB3在一定程度上介导ox-LDL诱导的巨噬细胞凋亡，这表明TRB3可能参与易损动脉粥样硬化斑块的进展。
Tribble3 (TRB3), a mammalian homolog of Drosophila tribbles, slows cell-cycle progression, and its expression is increased in response to various stresses. The aim of this study was to investigate the role of the TRB3 gene in macrophage apoptosis induced by oxidized low-density lipoprotein (ox-LDL). We found that, in human monocyte-derived macrophages, TRB3 is upregulated by ox-LDL in a dose- and time-dependent manner. The cell viability of TRB3-overexpressing macrophages was decreased, but apoptosis was increased and the level of activated caspase-3 increased. Factorial analyses revealed no significant interaction between TRB3 overexpression and ox-LDL stimulation with respect to macrophage apoptosis. Furthermore, TRB3-silenced macrophages showed decreased apoptosis, and TRB3-silenced cells treated with ox-LDL showed significantly increased apoptosis. Silencing of TRB3 and ox-LDL stimulation showed significant interaction for macrophage apoptosis, suggesting that TRB3 knockdown resisted the macrophage apoptosis induced by ox-LDL. Therefore, TRB3 in part mediates the macrophage apoptosis induced by ox-LDL, which suggests that TRB3 might be involved in vulnerable atherosclerotic plaque progression.