Lipid binding to sterol carrier protein-2 is inhibited by ethanol
Lipid binding to sterol carrier protein-2 is inhibited by ethanol
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DOI：
10.1016/s0005-2760(98)00178-7
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发表时间：
1999-01-29
影响因子：
4.8
通讯作者：
Wood, WG
中科院分区：
文献类型：
--
作者：
Avdulov, NA;Chochina, SV;Wood, WG
甾醇载体蛋白-2 （SCP-2）是一种细胞内脂质载体蛋白，可结合胆固醇、磷脂、脂肪酸等配体。有报道称，慢性乙醇处理小鼠的脑神经末梢或突触体中SCP-2的表达增加，并表明慢性乙醇处理动物的脑膜中胆固醇稳态发生改变。乙醇可能会干扰SCP-2结合胆固醇和其他脂质的能力。这个假设用重组SCP-2和荧光标记的胆固醇、磷脂酰胆碱（PC）和硬脂酸进行了验证。配体- scp -2复合物的缔合常数（K-a）顺序为：nbd -胆固醇> NBD-PC > nbd -硬脂酸。浓度为25 mM的乙醇显著降低了nbd -胆固醇和NBD-PC对SCP-2的亲和力。乙醇对nbd硬脂酸K-a的影响只有在检测的最高浓度（200 mM）时才显著。乙醇显著增加了SCP-2的nbd -胆固醇的B-max，但对NBD-PC的B-max没有显著影响。使用芘标记的胆固醇和PC，乙醇对K(a)s和B(max)s的影响也发现了类似的结果。综上所述，生理浓度为25mm的乙醇抑制了胆固醇和PC与SCP-2的结合。然而，乙醇对脂质与SCP-2结合的影响取决于脂质的类型。体内的乙醇可能干扰脂质与SCP-2的结合并破坏细胞内的脂质运输。(C) 1999 Elsevier Science B.V.版权所有
Sterol carrier protein-2 (SCP-2) is an intracellular lipid carrier protein that binds cholesterol, phospholipids, fatty acids and other ligands. It has been reported that expression of SCP-2 was increased in brain nerve endings or synaptosomes of chronic ethanol-treated mice and it was shown that cholesterol homeostasis was altered in brain membranes of chronic ethanol-treated animals. Ethanol may interfere with the capacity of SCP-2 to bind cholesterol as well as other lipids. This hypothesis was tested using recombinant SCP-2 and fluorescent-labeled cholesterol, phosphatidylcholine (PC), and stearic acid. The association constants (K-a) of the ligand-SCP-2 complex were in the following order: NBD-cholesterol > NBD-PC > NBD-stearic acid. Ethanol, beginning at a concentration of 25 mM, significantly reduced the affinity of NBD-cholesterol and NBD-PC for SCP-2. Effects of ethanol on the K-a of NBD-stearic acid was significant only at the highest concentration that was examined (200 mM). Ethanol significantly increased the B-max of NBD-cholesterol for SCP-2 but did not have a significant effect on the B-max of NBD-PC. Similar results were found for effects of ethanol on the K(a)s and B(max)s using pyrene-labeled cholesterol and PC. In conclusion, ethanol beginning at a physiological concentration of 25 mM inhibited binding of cholesterol and PC to SCP-2. However, effects of ethanol on lipid binding to SCP-2 were dependent on the type of lipid. Ethanol in vivo may interfere with lipid binding to SCP-2 and disrupt lipid trafficking within cells. (C) 1999 Elsevier Science B.V. All rights reserved.