氧化LDL通过PPARgamma的连接体激活来调节巨细胞基因表达
L Nagy1, P Tontonoz, J G Alvarez
1The Salk Institute of Biological Studies, Howard Hughes Medical Institute, La Jolla, California 92037, USA.
Cell
|May 6, 1998
概括
巨细胞的氧化LDL吸收触发了一种新的途径,激活PPARgamma. 特定的氧化脂质,9-HODE和13-HODE,作为内源的PPARgamma配体,可能调节动脉样硬化中的泡细胞基因表达.
科学领域:
- 分子生物学分子生物学
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
背景情况:
- 大细胞对氧化低密度脂蛋白 (oxLDL) 的吸收与泡细胞形成和动脉样硬化有关.
- 将oxLDL与细胞反应联系在一起的精确分子机制仍在研究中.
研究的目的:
- 阐明oxLDL激活PPAR玛依赖转录的信号通路.
- 在oxLDL.DL中识别PPARgamma的内源性配体.
主要方法:
- 调查的掠食者受体介导的oxLDL吸收.
- 分析了PPAR玛依赖的转录激活.
- 鉴定和描述了oxLDL的脂质成分作为PPARgamma配体.
主要成果:
- 已证明oxLDL通过食尸体受体介导吸收来激活PPARgamma.
- 确定了9-HODE和13-HODE作为主要的oxLDL组成部分和内源的PPARgamma激活剂/连接体.
- 为oxLDL的生物效应提出了一种双受体模型.
结论:
- PPARgamma可能是泡细胞基因表达的关键调节者.
- 氧化脂类成分的oxLDL直接激活核受体.
- 了解这种途径为动脉样硬化提供了潜在的治疗点.
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