Apolipoprotein A-I carboxy-terminal domain residues 187-243 are required for adiponectin-induced cholesterol efflux.
Apolipoprotein A-I carboxy-terminal domain residues 187-243 are required for adiponectin-induced cholesterol efflux.
复制标题
脂联素诱导的胆固醇流出需要载脂蛋白A-I羧基末端结构域残基187-243。
DOI：
10.1016/j.cellsig.2021.110222
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发表时间：
2022
影响因子：
4.8
通讯作者：
Daskalopoulou,StellaS
中科院分区：
文献类型：
--
作者：
Hafiane,Anouar;Gianopoulos,Ioanna;Sorci-Thomas,MaryG;Daskalopoulou,StellaS
脂联素通过刺激三磷酸腺苷结合盒转运体A1（ABCA 1）介导的胆固醇流出至载脂蛋白A-I（apoA-I）发挥其抗动脉粥样硬化作用。然而，在这一过程中的apoA-I残基的参与还没有研究。在Tamm-Horsfall 1（THP-1）巨噬细胞和幼仓鼠肾（BHK）细胞中，我们分别评估了脂联素在apoA-I和ABCA 1突变体存在下恢复胆固醇流出的潜力。脂联素不能恢复流出THP-1巨噬细胞在apoA-I羧基末端结构域（CTD）连续突变体的存在下，从残基187-243与apoA-I突变体单独。此外，脂联素没有显着影响胆固醇流出到apoA-I从BHK-ABCA 1突变细胞。脂联素似乎需要功能性apoA-I CTD残基187-243和野生型ABCA 1来分别介导THP-1巨噬细胞和BHK细胞的有效胆固醇流出。因此，脂联素不能挽救缺陷的胆固醇流出apoA-I或ABCA 1突变条件下，而是增加胆固醇流出野生型apoA-I条件下相比，apoA-I暴露单独。
Adiponectin exerts its atheroprotection by stimulating adenosine triphosphate binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux to apolipoprotein A-I (apoA-I). However, involvement of the apoA-I residues in this process have not been studied. In Tamm-Horsfall 1 (THP-1) macrophages and baby hamster kidney (BHK) cells we assessed adiponectin's potential to restore cholesterol efflux in the presence of apoA-I and ABCA1 mutants, respectively. Adiponectin was unable to restore efflux from THP-1 macrophages in the presence of apoA-I carboxy-terminal domain (CTD) successive mutants from residues 187–243 versus apoA-I mutants alone. Furthermore, adiponectin did not significantly influence cholesterol efflux to apoA-I from BHK-ABCA1 mutant cells. Adiponectin appears to require functional apoA-I CTD residues 187–243 and wild-type ABCA1 to mediate efficient cholesterol efflux from THP-1 macrophages and BHK cells, respectively. Therefore, adiponectin cannot rescue defective cholesterol efflux in apoA-I- or ABCA1-mutant conditions, but rather increases cholesterol efflux in wild-type apoA-I conditions compared to apoA-I exposure alone.