Apolipoprotein M affecting lipid metabolism or just catching a ride with lipoproteins in the circulation?

Apolipoprotein M (apoM) is a novel apolipoprotein found mainly in high-density lipoproteins (HDL). Its function is yet to be defined. ApoM (25 kDa) has a typical lipocalin ?-barrel fold and a hydrophobic pocket. Retinoids bind apoM but with low affinity and may not be the natural ligands. ApoM retains its signal peptide, which serves as a hydrophobic anchor to the lipoproteins. This prevents apoM from being lost in the urine. Approximately 5% of HDL carries an apoM molecule. ApoM in plasma (1 μM) correlates strongly with both low-density lipoprotein (LDL) and HDL cholesterol, suggesting a link to cholesterol metabolism. However, in casecontrol studies, apoM levels in patients with coronary heart disease (CHD) and controls were similar, suggesting apoM levels not to affect the risk for CHD in humans. Experiments in transgenic mice suggested apoM to have antiatherogenic properties; possible mechanisms include increased formation of pre-? HDL, enhanced cholesterol mobilization from foam cells, and increased antioxidant properties. Received 28 November 2008; received after revision 15 December 2008; accepted 16 December 2008     

载脂蛋白E定量测定的实验评价及临床应用

目的 :评价定量测定载脂蛋白E免疫比浊法 (液体双试剂 )的实验性能 ,讨论载脂蛋白E在心脑血管疾病及老年性痴呆症发病中的作用。方法 :对测定血清载脂蛋白E免疫比浊法的线性、精密度、回收、对比、重复性试验进行测定。正常对照组 12 0例 ,分 4组 ,每 15周岁为一组 ,每组进行载脂蛋白E的测定 ;心肌梗死、脑梗塞各 2 4例 ,高血压 67例 ,老年性痴呆症 2 0例和正常对照组 12 0例 ,分别检测血清脂蛋白 (a) (Lp(a) )、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL c)、低密度脂蛋白胆固醇 (LDL c)、载脂蛋白A1(apoA1)、载脂蛋白B(apoB)、载脂蛋白E(apoE) ,对检测结果做统计学分析。结果 :免疫比浊法线性范围为 0～ 10mg/dL ,Y =0 .93 87X + 0 .3 4,r =0 .9972 ;三种不同浓度的血清精密度试验批内CV值分别是2 .85 %、2 .0 6%、2 .47% ;批间CV值分别为 4.0 1%、3 .89%、3 .67% ;内加入法平均回收率为 10 0 .14% ,两种试剂对比试验 ,Y =0 .93 4X - 0 .0 75 ,r=0 .988;重复性试验其批内批间CV值分别为 3 .12 %、3 .98%。正常对照组 4组间进行比较 ,P >0 .0 5 ,各组分别与文献报道结果比较 ,P >0 .0 5 ,无显著性差异 ;心梗与脑梗血清中apoE、Lp(a)、TG、apoB均升高 ,与正常对照组间差异显著 ,P <0 .0 5     

Biological activity and pathological implications of misfolded proteins

The physiological metabolism of proteins guarantees that different cellular compartments contain the appropriate concentration of proteins to perform their biological functions and, after a variable period of wear and tear, mediates their natural catabolism. The equilibrium between protein synthesis and catabolism ensures an effective turnover, but hereditary or acquired abnormalities of protein structure can provoke a premature loss of biological function, an accelerated catabolism and diseases caused by the loss of an irreplaceable function. In certain proteins, abnormal structure and metabolism are associated with a strong tendency to self-aggregation into a polymeric fibrillar structure, and in these cases the disease is not principally caused by the loss of an irreplaceable function but by the action of this new biological entity. Amyloid fibrils are an apparently inert, insoluble, mainly extracellular protein polymer that kills the cell without tissue necrosis but by activation of the apoptotic mechanism. We analyzed the data reported so far on the structural and functional properties of four prototypic proteins with well-known biological functions (lysozyme, transthyretin, β2-microglobulin and apolipoprotein AI) that are able to create amyloid fibrils under certain conditions, with the perspective of evaluating whether the achievement of biological function favors or inhibits the process of fibril formation. Furthermore, studying the biological functions carried out by amyloid fibrils reveals new types of protein-protein interactions in the transmission of messages to cells and may provide new ideas for effective therapeutic strategies. Received 9 November 1998; received after revision 15 January 1999; accepted 15 January 1999     

胞嘧啶脱氨基酶APOBEC1研究进展

为全面理解载脂蛋白B mRNA(ApoB mRNA)编辑酶催化多肽-1(APOBEC1)的作用机制,介绍了APOBEC1和ApoB mRNA的蛋白及核酸序列,总结并绘制了APOBEC1与不同的辅助蛋白的结合模型,阐述了APOBEC1催化ApoB mRNA第6 666位的胞嘧啶(C_(6666))脱氨基化分子机制.列举了啮齿动物APOBEC1抑制多种逆转录病毒的研究报道,介绍了兔源APOBEC1结合人类免疫缺陷病毒1(HIV-1)的病毒粒子并编辑病毒基因组的机理.同时介绍了APOBEC1通过编辑胞嘧啶或与AU富集元件(ARE)结合来调控癌症等疾病相关的细胞因子表达.     

高脂血症及冠心病患者载脂蛋白B基因多态性

对１０８例高脂血症患和１２８例正常血脂的载脂蛋白Ｂ基因ＸｂａⅠ多态性进行分析，结果显示：Ｘ＾＋（第２６外显子存在多态切点）基因频率为０．０４，远低于西方高加索人种，Ｘ＾－（无多态切点）基因频率为０．９６。无论正常血脂组或高血脂组，不同基因型（Ｘ＾＋Ｘ＾－）的血浆总胆固醇及甘油三酯水平差别均不显，高血脂组与正常血脂组相比，Ｘ＾＋Ｘ＾－与Ｘ＾－Ｘ＾－的发生频率差别也无显性。冠心病患６９例与对     

The role of apolipoprotein E in lipid metabolism in the central nervous system

The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover, although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004     

载脂蛋白E基因多态性PCR─RFLP方法的建立

目的：建立一种省时、省力的人载脂蛋白E基因多态性的检测方法。方法：采用聚合酶链—限制性片段长度多态性（PCR－RFLP）方法,先扩增出apoE基因第4外显子内的272bp片段,继以限制性内切酶CfoⅠ酶解消化,8％聚丙烯酰胺凝胶电泳,最后银染显带判定基因型。结果：电泳、染色结果清晰、特异、分辨率高。结论：该方法快速、准确、适于临床实验室中广泛开展。     

健身长跑对中老年人血脂代谢的影响

测量和比较45例和对照组44例进行血脂、脂蛋白及载脂蛋白水平的差异.试验结果显示,两组间胆固醇(TC)、甘油三酯(TG)水平无显著差异(P>0.05),健身跑组低密度脂蛋白胆固醇(LDL C)值则显著高于对照组(P<0.05),高密度脂蛋白(LDL C)高于对照组(P<0.05).研究结果表明,经过长跑训练,对血脂异常具有良好的调节作用.