The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-κB in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7
The orphan nuclear receptor small heterodimer partner as a novel coregulator of nuclear factor-κB in oxidized low density lipoprotein-treated macrophage cell line RAW 264.7
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DOI：
10.1074/jbc.m101977200
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发表时间：
2001-09-07
影响因子：
4.8
通讯作者：
Pak, YK
中科院分区：
文献类型：
--
作者：
Kim, YS;Han, CY;Pak, YK
小异二聚体伴侣 (SHP) 在肝脏和有限数量的其他组织中特异性表达，是一种不寻常的孤儿核受体，缺乏传统的 DNA 结合域。在这项工作中，我们发现 SHP 表达在鼠巨噬细胞系 RAW 264.7 中丰富，但被氧化低密度脂蛋白 (oxLDL) 及其成分 13-羟基十八二烯酸（过氧化物酶体增殖物激活受体 γ 的配体）抑制。此外，SHP 充当核因子 kappaB (NF kappaB) 的转录共激活子，对于之前描述的棕榈酰溶血胆碱（oxLDL 成分之一）的 NF kappaB 反式激活至关重要。因此，NF kappaB（一开始具有转录活性）在 oxLDL 处理的 RAW 264.7 细胞中逐渐变得惰性，因为 oxLDL 降低了 SHP 表达。因此，SBP 似乎是调节 oxLDL 处理的静息巨噬细胞中 NF kappaB 转录活性的重要调节成分。
Small heterodimer partner (SHP), specifically expressed in liver and a limited number of other tissues, is an unusual orphan nuclear receptor that lacks the conventional DNA binding domain. In this work, we found that SHP expression is abundant in murine macrophage cell line RAW 264.7 but was suppressed by oxidized low density lipoprotein (oxLDL) and its constituent 13-hydroxyoctadecadienoic acid, a ligand for peroxisome proliferator-activated receptor gamma. Furthermore, SHP acted as a transcription coactivator of nuclear factor-kappaB (NF kappaB) and was essential for the previously described NF kappaB transactivation by palmitoyl lysophosphaticlylcholine, one of the oxLDL constituents. Accordingly NF kappaB, which was transcriptionally active in the beginning, became progressively inert in oxLDL-treated RAW 264.7 cells as oxLDL decreased the SHP expression. Thus, SBP appears to be an important modulatory component to regulate the transcriptional activities of NF kappaB in oxLDL-treated, resting macrophage cells.