载脂蛋白M的研究进展

载脂蛋白M(apoM)是一种新发现的载脂蛋白 ,蛋白结构属于Lipocalin超家族 ,分子量约 2 4KD ,有一糖基侧链 ,人类apoM基因定位于人类 6号染色体短臂 ,紧邻MHC Ⅲ ,特异选择地在肝脏细胞和肾脏近曲小管上皮细胞中表达 ,在血液中apoM主要存在于高密度脂蛋白、少量在富含甘油三酯脂蛋白和低密度脂蛋白中。apoM在细胞内的表达调控及其生理、病理功能尚有待进一步研究。     

甲基泼尼松龙对肾癌细胞株786-0载脂蛋白M的影响

目的:研究甲基泼尼松龙对肾癌细胞株786鄄0分泌载脂蛋白M(apoM)的影响。方法:体外培养肾透明细胞癌细胞株786鄄0,以不同浓度的甲强龙作用于对数分裂期的细胞24h,WesternBlot检测细胞培养基中的apoM,分离提纯细胞总RNA,逆转录为cDNA,实时定量多聚酶链反应(RT鄄PCR)检测细胞中apoMmRNA的含量。结果:甲基泼尼松龙浓度为250或375滋g/ml时,能刺激细胞内apoMmRNA转录,促进细胞分泌apoM。结论:甲基泼尼松龙能明显影响细胞株786鄄0apoMmRNA的转录和apoM的分泌。     

Apolipoprotein M: Progress in understanding its regulation and metabolic functions

ApoM is a novel apolipoprotein mainly present in high‐density lipoprotein (HDL). It belongs to the lipocalin protein superfamily and may bind a small but so far unknown lipophilic ligand. It is secreted without cleavage of its hydrophobic signal peptide, which probably anchors apoM in the phospholipid moiety of plasma lipoproteins. Recent studies suggest that apoM may affect HDL metabolism and have anti‐atherogenic functions. The subfraction of human HDL that contains apoM therefore protects LDL from oxidation and mediates cholesterol efflux more efficiently then HDL without apoM. In addition to hepatocytes, apoM is highly expressed in kidney proximal tubule cells. Recent data suggest that apoM is secreted into the pre‐urine from the tubule cells but is normally taken up again in a megalin‐dependent fashion. Further studies of mice with genetically modified apoM expression will be essential to unravel the potential roles of apoM in lipoprotein metabolism, atherosclerosis and kidney biology.     

Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism

Background

Apolipoprotein M (apoM) has been identified as a specific sphingosine-1-phosphate (S1P) binding protein of HDL.

Objectives and methods

To investigate the in vivo effects of disturbed apoM or HDL metabolism we quantified S1P and apoM in plasmas of wild-type, apoM-knock-out, and apoM transgenic mice as well as 50 patients with seven different monogenic disorders of HDL metabolism and their 51 unaffected relatives.

Results

Compared to wild type mice, S1P plasma levels in apoM knock-out and apoM transgenic mice were decreased by 30% and increased by 270%, respectively. Compared to family controls, S1P and apoM levels in apoB-depleted plasma were significantly decreased by in average 34% and 12%, respectively, in heterozygous carriers of mutations in APOA1, LCAT or ABCA1, and by 70% and 48%, respectively, in carriers of two defective alleles in LCAT or ABCA1. Heterozygous mutations in CETP, SCARB1, LIPC, or LIPG did not significantly affect S1P or apoM concentrations. Albumin-corrected molar S1P-to-apoM ratios varied from 0.12 to 0.8 (median 0.3) and were not affected by any mutation. S1P levels in apoB-depleted plasma correlated significantly with HDL-cholesterol and less so with apoM both if apoA-I plasma concentrations were below the median.

Conclusion

In the context of previous data, our findings can be explained by the existence of a specific apoM and S1P containing HDL subclass which contains a considerable molar excess of apoM over S1P and is critically determined by apoA-I up to a threshold concentration around the median found in a Caucasian population.