The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway
The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway
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DOI：
10.1172/jci8119
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发表时间：
1999-10-01
影响因子：
15.9
通讯作者：
Oram, JF
中科院分区：
文献类型：
--
作者：
Lawn, RM;Wade, DP;Oram, JF
ABC1转运蛋白被确定为丹吉尔病的基因表达微阵列分析，遗传图谱和生化研究的组合策略的缺陷。丹吉尔病患者在细胞胆固醇清除方面存在缺陷，这导致HDL的血浆水平接近于零，并导致胆固醇酯的大量组织沉积。阻断ABC1的表达或活性可减少载脂蛋白介导的脂质从培养细胞中流出，增加ABC1的表达可增强ABC1的表达。该蛋白质与其表达水平成比例地掺入质膜中。在3例无关患者的ABC1基因中检测到不同突变。因此，ABC1具有细胞脂质清除途径中的关键蛋白质的性质，正如其在丹吉尔病患者中的缺陷所强调的那样。
The ABC1 transporter was identified as the defect in Tangier disease by a combined strategy of gene expression microarray analysis, genetic mapping, and biochemical studies. Patients with Tangier disease have a defect in cellular cholesterol removal, which results in near zero plasma levels of HDL and in massive tissue deposition of cholesteryl esters. Blocking the expression or activity of ABC1 reduces apolipoprotein-mediated lipid efflux from cultured cells, and increasing expression of ABC1 enhances it. ABC1 expression is induced by cholesterol loading and cAMP treatment and is reduced upon subsequent cholesterol removal by apolipoproteins. The protein is incorporated into the plasma membrane in proportion to its level of expression. Different mutations were detected in the ABC1 gene of 3 unrelated patients. Thus, ABC1 has the properties of a key protein in the cellular lipid removal pathway, as emphasized by the consequences of its defect in patients with Tangier disease.