Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation
Helical apolipoproteins stabilize ATP-binding cassette transporter A1 by protecting it from thiol protease-mediated degradation
复制标题
DOI：
10.1074/jbc.m202996200
复制
发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Yokoyama, S
中科院分区：
文献类型：
--
作者：
Arakawa, R;Yokoyama, S
在THP-1细胞中，载脂蛋白A-I可使ATP结合盒转运体(ABC)A1增加，但不增加其信息传递。脉冲标记研究表明apoA-I延缓了ABCA1的降解。ApoA-II也表现出类似的变化，但在等量蛋白质浓度的基础上，高密度脂蛋白的影响几乎可以忽略不计。硫醇蛋白水解酶抑制剂(亮肽素和N-乙酰-亮氨酸-去甲亮氨酸(ALLN))可增加ABCA1并减缓其在细胞中的衰退，而蛋白酶体特异性抑制剂lactacystin、其他蛋白酶抑制剂或溶酶体抑制剂NH4Cl均未显示出这种作用。ApoA-I和ALLN对ApoA-I、U_i的升高有相加作用，All-N可促进ApoA-I介导的细胞内脂质释放。这些数据表明，ABCA1会被细胞中的一种硫醇蛋白酶(S)迅速降解，除非无脂形式的螺旋载脂蛋白通过保护ABCA1免受蛋白酶介导的降解而稳定它。
ATP-binding cassette transporter (ABC) A1 was increased by apolipoprotein A-I without an increase of its message in THP-1 cells. The pulse label study demonstrated that apoA-I retarded degradation of ABCA1. Similar changes were demonstrated by apoA-II, but the effect of high density lipoprotein was almost negligible on the basis of equivalent protein concentration. Thiol protease inhibitors (leupeptin and N-acetyl-Leu-Leu-norleucinal (ALLN)) increased ABCA1 and slowed its decay in the cells, whereas none of the proteosome-specific inhibitor lactacystin, other protease inhibitors, or the lysosomal inhibitor NH4Cl showed such effects. The effects of apoA-I and ALLN were additive for the increase of ABC.,U,, and the apoA-I-mediated cellular lipid release was enhanced by ALLN. The data suggest that ABCA1 is rapidly degraded by a thiol protease(s) in the cells unless helical apolipoproteins in their lipid-free form stabilize ABCA1 by protecting it from protease-mediated degradation.