Regulation of acyl-coenzyme A:cholesterol acyltransferase (ACAT) synthesis, degradation, and translocation by high-density lipoprotein(2) at a low concentration.
Regulation of acyl-coenzyme A:cholesterol acyltransferase (ACAT) synthesis, degradation, and translocation by high-density lipoprotein(2) at a low concentration.
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低浓度高密度脂蛋白 (2) 对酰基辅酶 A：胆固醇酰基转移酶 (ACAT) 合成、降解和易位的调节。
DOI：
10.1161/01.atv.20.12.2636
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Pownall,HJ
中科院分区：
文献类型：
--
作者：
Li,L;Pownall,HJ
虽然血浆HDL-2胆固醇浓度与动脉粥样硬化疾病的风险呈负相关，但对明显的心脏保护机制知之甚少。在小鼠P388 D1巨噬细胞中，低浓度（≤40 μg/mL）的HDL 2抑制巨噬细胞酰基辅酶A：胆固醇酰基转移酶（ACAT），该酶催化细胞内胆固醇的酯化。在小鼠P388 D1巨噬细胞中研究了HDL 2对ACAT合成、降解和胞内转运的影响。低浓度HDL 2促进ACAT合成，但对ACAT总质量无影响。免疫细胞化学研究表明，在脂蛋白的情况下，ACAT主要与细胞的核周区域。然而，添加HDL 2诱导ACAT转移到囊泡结构和邻近质膜的细胞周边。亚分级结合免疫沉淀补充了这些观察结果，并表明HDL 2促进ACAT转移到质膜组分。布雷菲德菌素A，抑制囊泡蛋白运输从内质网到高尔基体区室在哺乳动物细胞，阻断ACAT易位和部分恢复ACAT活性。这些结果表明，HDL 2是一个启动因子的信号转导途径，导致细胞内ACAT的易位和失活。
—Although plasma HDL2cholesterol concentration stands in inverse relation to risk for atherosclerotic disease, little is known about the mechanism of the apparent cardioprotection. In mouse P388D1 macrophages, HDL2at a low concentration (≤40 μg/mL) inhibits macrophage acyl-coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyzes esterification of intracellular cholesterol. The effects of HDL2on ACAT synthesis, degradation, and intracellular translocation were investigated in mouse P388D1 macrophages. HDL2at a low concentration enhanced ACAT synthesis but not total ACAT mass. Immunocytochemical studies showed that in the absence of lipoproteins, ACAT associated primarily with the perinuclear region of the cell. The addition of HDL2, however, induced the transfer of ACAT to vesicular structures and the cell periphery adjacent to the plasma membrane. Subfractionation combined with immunoprecipitation complemented these observations and showed that HDL2promoted the transfer of ACAT to the plasma membrane fraction. Brefeldin A, which inhibits vesicular protein transport from the endoplasmic reticulum to the Golgi compartment in mammalian cells, blocked ACAT translocation and partially restored ACAT activity. These results suggest that HDL2is an initiating factor in a signal transduction pathway that leads to intracellular ACAT translocation and inactivation.