Peng S K, Zhang X, Chai N N, Wan Y, Morin R J
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, USA.
Artery. 1996;22(2):61-79.
The effects of the cholesterol oxides on low density lipoprotein receptor (LDLR) gene expression were investigated. Cultured rabbit aortic smooth muscle cells were incubated with 1, 2, and 5 micrograms/ml culture medium concentrations of pure cholesterol, 25-hydroxycholesterol (25-OH), 7-ketocholesterol (7-keto), cholestane-3 beta, 5 alpha, 6 beta-triol (triol) and cholesterol-5 alpha, 6 alpha-epoxide (epoxide) for 12 hours and with vehicle only as control. Total mRNAs were extracted and electrophoresed. Northern blot hybridization analyses were performed. The results showed mRNA expressions of LDLR gene were inhibited to 16.1 +/- 4.4%, 33.8 +/- 0.6%, 42.8 +/- 1.8% and 46.9 +/- 3.9% of control by 25-OH, 7-keto, epoxide and triol respectively. Pure cholesterol showed only minimal inhibition. The inhibitions were time dependent. Although cholesterol oxides have been shown to alter many membrane-related functions and the LDLR domain are located in the cell membrane. The findings of this study suggested that the cholesterol oxides exerted their repressive actions on LDLR function primarily by down-regulating LDLR gene expression rather than directly upon cell membrane.
研究了胆固醇氧化物对低密度脂蛋白受体（LDLR）基因表达的影响。将培养的兔主动脉平滑肌细胞与培养基中浓度分别为1、2和5微克/毫升的纯胆固醇、25-羟基胆固醇（25-OH）、7-酮胆固醇（7-酮）、胆甾烷-3β,5α,6β-三醇（三醇）和胆固醇-5α,6α-环氧化物（环氧化物）孵育12小时，仅以溶剂作为对照。提取总mRNA并进行电泳。进行Northern印迹杂交分析。结果显示，25-OH、7-酮、环氧化物和三醇分别将LDLR基因的mRNA表达抑制至对照的16.1±4.4%、33.8±0.6%、42.8±1.8%和46.9±3.9%。纯胆固醇仅显示出最小程度的抑制。这些抑制作用具有时间依赖性。尽管胆固醇氧化物已被证明可改变许多与膜相关的功能，且LDLR结构域位于细胞膜中。本研究结果表明，胆固醇氧化物对LDLR功能的抑制作用主要是通过下调LDLR基因表达，而非直接作用于细胞膜。
