A synonymous variant in scavenger receptor, class B, type I gene is associated with lower SR-BI protein expression and function.
A synonymous variant in scavenger receptor, class B, type I gene is associated with lower SR-BI protein expression and function.
复制标题
清道夫受体B类，I型基因中的同义变体与较低的SR-BI蛋白表达和功能有关。
DOI：
10.1016/j.atherosclerosis.2009.11.029
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发表时间：
2010-05
期刊：
影响因子：
5.3
通讯作者：
Rodriguez, Annabelle
中科院分区：
文献类型：
--
作者：
Constantineau, Jason;Greason, Erin;West, Michael;Filbin, Megan;Kieft, Jeffrey S.;Carletti, Martha Z.;Christenson, Lane K.;Rodriguez, Annabelle
清道夫受体B I型基因（SCARB 1）第8外显子rs 5888的同义变异与人类血脂水平改变和心血管风险相关。目的是确定rs 5888是否在体外降低SR-BI蛋白表达和功能。在用野生型或rs 5888-SR-BI质粒转染的COS细胞中，通过选择性2 '-羟基酰化和引物延伸测定、放线菌素D抑制、多聚核糖体分析和蛋白质印迹法检查SR-BI RNA二级结构、转换、多聚核糖体分布和蛋白质表达。通过测量125 I，3 H-胆固醇酯（CE）放射性标记的HDL的特异性细胞结合来评估稳定表达野生型或rs 5888-SR-BI的鼠巨噬细胞中的SR-BI功能。Rs 5888改变了RNA二级结构，并导致与野生型转录本相比多聚体谱的显著差异（p<0.02）。与野生型细胞相比，表达rs 5888的COS细胞具有显著较低的SR-BI蛋白表达（p<0.04），但总RNA转录水平没有差异。在鼠巨噬细胞中SR-BI RNA周转没有差异，而在rs 5888细胞中125 I（p<0.0001）或3 H-CE（p<0.00001）的特异性细胞结合显著较低。rs 5888变异体影响SR-BI RNA二级结构、蛋白翻译，并与体外SR-BI蛋白表达和功能降低显著相关。
A synonymous variant within scavenger receptor class B type I gene (SCARB1), exon 8 rs5888, has been associated with altered lipid levels and cardiovascular risk in humans. The objective was to determine if rs5888 decreased SR-BI protein expression and function in vitro. SR-BI RNA secondary structure, turnover, polysomal distribution and protein expression were examined in COS cells transfected with wild-type or rs5888-SR-BI plasmids by selective 2’-hydroxyl acylation and primer extension assays, actinomycin D inhibition, polysomal profiling, and western blotting. SR-BI function in murine macrophages stably expressing wild-type or rs5888-SR-BI was assessed by measuring the specific cell association of 125I,3H-cholesteryl ester (CE) radiolabeled HDL. Rs5888 changed RNA secondary structure and led to marked differences in the polysomal profiles compared with wild-type transcript (p<0.02). As compared to wild-type cells, COS cells expressing rs5888 had significantly lower SR-BI protein expression (p<0.04), but no difference in total RNA transcript levels. There were no differences in SR-BI RNA turnover in murine macrophages, whereas specific cell association of 125I (p<0.0001) or 3H-CE (p<0.00001) was significantly lower in rs5888 cells. The rs5888 variant affected SR-BI RNA secondary structure, protein translation, and was significantly associated with reduced SR-BI protein expression and function in vitro.
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影响因子：
--
作者：
Cao, GQ;Zhao, LP;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
15.9
作者：
Landschulz, KT;Pathak, RK;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
5.3
作者：
Richard, E;von Muhlen, D;McCarthy, JJ
通讯作者：
McCarthy, JJ
影响因子：
5
作者：
SCHRIEWER, H;JABS, HU;ASSMANN, G
通讯作者：
ASSMANN, G
影响因子：
8
作者：
Signori, E;Bagni, C;Fazio, VM
通讯作者：
Fazio, VM