Xu Ning, Zhang Xiao-Ying, Dong Xuan, Ekström Ulf, Ye Qing, Nilsson-Ehle Peter
Department of Clinical Chemistry, University Hospital of Lund, Lund, S-221 85, Sweden.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):944-50. doi: 10.1006/bbrc.2002.6755.
Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL) in plasma, exclusively expressed in liver and in kidney. The function of apoM is yet unknown. The human apoM gene is located in the major histocompatibility complex class III region on chromosome 6. Because many genes located in this region are related to the immune response, we have investigated whether apoM might also be involved in the host inflammatory response. In this study we examined effects of the platelet-activating factor (PAF), tumor necrosis factor (TNF-alpha), and interleukin-1alpha (IL-1alpha) on apoM expression in a hepatoblastoma cell line, HepG2 cells. PAF significantly enhanced the apoM mRNA levels and the secretion of apoM in HepG2 cell cultures. The enhancement of apoM secretion is seen at a low concentration of PAF (2 ng/ml), whereas a high concentration of PAF increases both the apoM mRNA levels and apoM secretion. Neither TNF-alpha nor IL-1alpha influenced apoM mRNA level and secretion. Furthermore, Lexipafant, a PAF-receptor (PAF-R) antagonist significantly suppressed the mRNA level and the secretion of apoM in HepG2 cells in a dose-dependent manner. Neither PAF nor Lexipafant influenced the mRNA levels and the secretion of apoA-I, apoB and apoE in HepG2 cells, indicating that the effects of PAF or Lexipafant on the apoM production on hepatic cells are selective for apoM. The cellular mechanism of the effects of PAF or Lexipafant on apoM metabolism requires further investigations.
载脂蛋白M（apoM）是一种最近发现的人类载脂蛋白，主要存在于血浆中的高密度脂蛋白（HDL）中，仅在肝脏和肾脏中表达。apoM的功能尚不清楚。人类apoM基因位于6号染色体上的主要组织相容性复合体III类区域。由于位于该区域的许多基因与免疫反应有关，我们研究了apoM是否也可能参与宿主炎症反应。在本研究中，我们检测了血小板活化因子（PAF）、肿瘤坏死因子（TNF-α）和白细胞介素-1α（IL-1α）对人肝癌细胞系HepG2细胞中apoM表达的影响。PAF显著提高了HepG2细胞培养物中apoM的mRNA水平和apoM的分泌。在低浓度PAF（2 ng/ml）时即可观察到apoM分泌的增加，而高浓度PAF则同时增加apoM的mRNA水平和apoM分泌。TNF-α和IL-1α均未影响apoM的mRNA水平和分泌。此外，PAF受体（PAF-R）拮抗剂来昔帕泛以剂量依赖的方式显著抑制了HepG2细胞中apoM的mRNA水平和分泌。PAF和来昔帕泛均未影响HepG2细胞中apoA-I、apoB和apoE的mRNA水平和分泌，表明PAF或来昔帕泛对肝细胞中apoM产生的影响对apoM具有选择性。PAF或来昔帕泛对apoM代谢影响的细胞机制需要进一步研究。
