Elevation of ceramide in serum lipoproteins during acute phase response in humans and mice: role of serine-palmitoyl transferase
Elevation of ceramide in serum lipoproteins during acute phase response in humans and mice: role of serine-palmitoyl transferase
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DOI：
10.1016/j.abb.2003.08.031
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发表时间：
2003-11-15
影响因子：
3.9
通讯作者：
Nikolova-Karakashian, M
中科院分区：
文献类型：
--
作者：
Lightle, S;Tosheva, R;Nikolova-Karakashian, M
最近的研究表明，在肝脏中产生的神经酰胺作为极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）的组分分泌到血流中。本文研究了宿主急性期炎症反应对脂蛋白神经酰胺水平的影响。在人类中，发现了两种不同的反应模式，一组志愿者在LPS给药后1.5小时血清神经酰胺短暂升高。第二组显示出延长的增加，达到基础水平的10倍以上，并持续长达24小时。仅在VLDL和LDL颗粒中发现神经酰胺增加。LPS给药在小鼠中诱导了类似的增加。这些增加伴随着血清中分泌的鞘磷脂酶和肝脏中丝氨酸棕榈酰转移酶的激活。ASMase敲除小鼠保留了LPS诱导的血清神经酰胺增加，因此表明VLDL和LDL神经酰胺含量的升高至少部分归因于肝脏中神经酰胺从头合成的激活。(C)2003年爱思唯尔公司All rights reserved.
Recent studies have indicated that ceramide generated in the liver is secreted into the bloodstream as component of very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). This manuscript investigates the effect of host acute phase response to inflammation on lipoprotein ceramide levels. In humans, two different patterns of responses were found. One group of volunteers experienced transient increases in serum ceramide at 1.5 h after LPS administration. Second group showed prolonged increases that reached up to 10-fold above the basal level and continued for up to 24 h. Increases in ceramide were found only in VLDL and LDL particles. LPS administration induced similar increases in mice. These increases were accompanied by activation of secreted sphingomyelinase in serum and serine-palmitoyl transferase in liver. ASMase knockout mice retained LPS-induced increases in serum ceramide, thus suggesting that the elevation of VLDL and LDL ceramide content is attributed at least in part to activation of de novo synthesis of ceramide in the liver. (C) 2003 Elsevier Inc. All rights reserved.