Cholesterol rich lipid raft microdomains are gateway for acute phase protein, SERPINA1.
Cholesterol rich lipid raft microdomains are gateway for acute phase protein, SERPINA1.
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富含胆固醇的脂筏微结构域是急性期蛋白 SERPINA1 的门户。
DOI：
10.1016/j.biocel.2010.06.009
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Janciauskiene,Sabina
中科院分区：
文献类型：
--
作者：
Subramaniyam,Devipriya;Zhou,Huiping;Liang,Min;Welte,Tobias;Mahadeva,Ravi;Janciauskiene,Sabina
Cholesterol is the most abundant lipid component of the plasma membrane, and thus the equilibrium between free cholesterol and raft cholesterol act as a determinant of raft function and cell signalling. The mechanisms that regulate the lipid raft cholesterol levels are largely unknown. Here we demonstrate that SERPINA1 (α1-antitrypsin), an acute phase protein and the classical neutrophil elastase inhibitor, is localized within lipid rafts in primary human monocytes in vitro. SERPINA1 association with monocytes is inhibited by cholesterol depleting/efflux-stimulating agents (nystatin, filipin, MβCD (methyl-beta-cyclodextrin) and oxidized low-density lipoprotein (oxLDL) and conversely, enhanced by free cholesterol. Furthermore, SERPINA1/monocyte association per se depletes lipid raft cholesterol as characterized by the activation of extracellular signal-regulated kinase 2, formation of cytosolic lipid droplets, and a complete inhibition of oxLDL uptake by monocytes. Our findings for the first time highlight that the entry and cell association of SERPINA1 is dependent on lipid raft cholesterol and that SERPINA1 depletes lipid raft cholesterol.
