National Institute for Health and Welfare, Public Health Genomics Research Unit and FIMM, Institute for Molecular Medicine Finland, Helsinki, Finland.
Lipids Health Dis. 2010 Jun 9;9:59. doi: 10.1186/1476-511X-9-59.
phospholipid transfer protein (PLTP) plays important roles in lipoprotein metabolism and atherosclerosis and is expressed by macrophages and macrophage foam cells (MFCs). The aim of the present study was to determine whether the major protein from HDL, apoA-I, affects PLTP derived from MFCs.
as cell model we used human THP-1 monocytes incubated with acetylated LDL, to generate MFC. The addition of apoA-I to the cell media increased apoE secretion from the cells, in a concentration dependent fashion, without affecting cellular apoE levels. In contrast, apoA-I had no effect on PLTP synthesis and secretion, but strongly induced the PLTP activity in the media. ApoA-I also increased phospholipid transfer activity of PLTP isolated from human plasma. This effect was dependent on apoA-I concentration but independent on apoA-I lipidation status. ApoE, ApoA-II and apoA-IV, but not immunoglobulins or bovine serum albumin, also increased PLTP activity. We also report that apoA-I protects PLTP from heat inactivation.
apoA-I enhances the phospholipid transfer activity of PLTP secreted from macrophage foam cells without affecting the PLTP mass.
磷脂转运蛋白(PLTP)在脂蛋白代谢和动脉粥样硬化中起着重要作用,由巨噬细胞和巨噬细胞泡沫细胞(MFC)表达。本研究旨在确定载脂蛋白 A-I(apoA-I)这一 HDL 的主要蛋白是否会影响源自 MFC 的 PLTP。
我们使用经乙酰化 LDL 孵育的人 THP-1 单核细胞作为细胞模型,以生成 MFC。apoA-I 以浓度依赖的方式添加到细胞培养基中,增加了细胞分泌的 apoE,但不影响细胞内 apoE 水平。相比之下,apoA-I 对 PLTP 的合成和分泌没有影响,但强烈诱导了培养基中的 PLTP 活性。apoA-I 还增加了从人血浆中分离的 PLTP 的磷脂转移活性。这种作用依赖于 apoA-I 的浓度,但与 apoA-I 的脂质化状态无关。apoE、apoA-II 和 apoA-IV 也能增加 PLTP 活性,但免疫球蛋白和牛血清白蛋白则不能。我们还报告称,apoA-I 可保护 PLTP 免受热失活。
apoA-I 增强了源自巨噬细胞泡沫细胞分泌的 PLTP 的磷脂转移活性,而不影响 PLTP 的质量。