仙一网 - 文献资料 - 医学书籍 - 动脉粥样硬化

第七节 载脂蛋白H

  人载脂蛋白H(human apolipoprotein H,ApoH)又称为β2糖蛋白Ⅰ(β2-glycoprotein,β2-GI),由Schultze等于1961年首先发现,它是人血浆中作为过氯酸可溶性部分存在的一种50kD糖蛋白。

  ApoH是由326个氨基酸残基组成的单链多肽,其中含量最丰富的是脯氨酸(共31个),半胱氨酸共有22个,与二硫键的形成有关。含有甘氨酸23个,并与胱氨酸共同形成高频β-转角所必需。ApoH分子量为50kD,具有寡聚多糖的结构,含有5个分支糖胺寡聚多糖侧链,糖链占整个蛋白质分子的19%,系由半乳糖,甘露糖、N-乙酰氨基葡萄糖、岩藻糖及N-乙酰神经氨酸组成。所有寡聚多糖均通过糖基受体序列Asn-X-Ser/Thr而连接到天冬酰胺位点上,分别位于143、164、169、174和234残基位置上。受体序列中间位的“X”为色氨酸(Trp),且这两个Trp在蛋白链中都为同源位点。

  因等位基因缺失可引起血清浓度异常,依此提出两个常染色体共显性等位基因-BgN(正常型)和BgD(缺失型)控制ApoH的表达模式:BgNBgN纯合子个体,其ApoH浓度在169~300mg/L;BgNBgD杂合子,血清浓度在60~140mg/L;而BgDBgD纯合子个体则<50mg/L。BgD缺失型等位基因出现频率在先天愚型人群中>20%,比健康人群要高。非遗传因素也可以起血清中ApoH含量的变化。因ApoH基因变异,其结构存在多态性,目前认为编码相关的三个普通等位基因即ApoH1、ApoH2和ApoH3、还有ApoH4的存在。三个常染色体的3个等位基因型决定了六种不同形式的表型,共同基因ApoH2出现频率高达90%。

  在人血浆中占总量60%的ApoH存在于离心后d>1.21g/ml底层部分的游离脂蛋白中,余下部分则主要存在于富含TG的脂蛋白中,是CM、VLDL、LDL和HDL的组成成分,又是LPL的激活剂。有报道,ApoH在ApoCⅡ存在时,能提高LPL活性45±17%,而ApoCⅢ则降低ApoH是ApoCⅡ赋予的LPL活性的77%。ApoH还参与凝血机制,因为ApoH与血小板结合,使磷脂带阴电荷,从而减少凝血因子Xa、Va、Ca++与凝血酶原的结合位点或凝血酶原结合到血小板膜上后,通过调节腺苷酸环化酶活性来抑制ADP介导的血小板凝集,它作为一种血浆抑制因子,抑制内源性凝血旁路的接触激活。

  在肾小管疾病中,ApoH的检测可作为早期肾小管损伤时的诊断指标,然而灵敏度尚不够高。

  健康人血浆中ApoH浓度为193±30mg/L。

(周新 郑芳)

  参 考 文 献

  1.王克勤主编,脂蛋白与动脉粥样硬化,北京:人民卫生出版社,1995

  2.Zannis V,Breslow J,Katz A,et al.Isoprotein of humnan apolipoprotein AI demonstrated in plasma and intestinal organ culture.J Biol Chem,1980,255:8612-8617

  3.Brewer H,et al The amino acid sequence of human Apoa I,an apolipoprotein isolated from high density lipoproteins .Biophy Res Commun,1978,80:623-630

  4.Schaerer E,et al.Human apolipoprotein AI and A Ⅱmetabolism,j Lipid Res,1982,23:850-862

  5.Steinmetz A,Vterman G.Activation of lectithin:cholesterol acyltransferase by human apolipoprotein A Ⅳ.J Biol chem,1985,260:2258-2264

  6. Bojanovski D,Gregg R,Ghiselli G,et al.Human apolipoprotein A I isoprotein metabolism:preapo A I conversion to mature ApoA I.J Lipid Res,1985-193

  7.Avogarpm,et al Aer apolipoproteins better discriminatory than lipids for atherosclerosis.Lancet,1979,1:901

  8.DeBacker G et al.Discriminatory valuc of ilpids and apoproteins in coronary heart disease.Atherosclerosis,1982,42:197

  9. Albers et al Immunoassay of hunan apolipoprotein B.Metab Chin Exp,1975,24:1339

  10.Noma A Plasma lipids and apolipoproteins as discriminators for presnce and severity of angiographically defined coronary artery disease.Atherosclerosis,1983,49:1

  11.周新,张华征,殷以礼等,抗人载脂蛋白B血清的制备及其临床应用,中华心血管病杂专,1986,14:135-137

  12.Yang C,Gu Z,Weng S,et al.Structure of apolipoprotein B100of human low density lipoproteins.Arteriosclerosis,1989,9:96-108

  13.Youg,S,Bertics S,Curtiss L,et al.Monochonal antibody MB19detcts genetic polymorphisn in human apolipoprotein B.Proc Natl Acad Sci USA,1986,83:1101-1105

  14.周新,张华征,韩豫等.人血清载脂蛋白C的分离与定量.科学通报,1984,29:437-440

  15.Brown W,Levy R,Frerickson Det al. Studies of the proteins in human plasma very low density lipoprotein .J Bio Chem,1970,245:6588-6594

  16.Blaufuss M,Cordon J,Schonfeld G et al.Biosynthesis of Apolipoprotein C-Ⅲin rat liver and smart intestinal macosa.J Biol Chem,1984,259:2452

  17.Yasuhisa I,Shunichi K,Hiroshi I,et al .Plasma levels of lipids and Apolipoproteins E phenotypic groups,Nature, 1985,269:605-608

  18.Utermann G,Langenbeck U,Beisiegel V,et al .Genetics of the apolipoprotein E sysem in man ,Am J,Hum Genet,1980,32:339-347

  19.Cristina C,Walden M.Robert A,et al.Apolipoprotein E in hyperlipidemia.Am Intern Med ,1994,120:1026-1036

  20.Dallongeville J.Cacan S,Davignon Jet al.Modulation of plasma triglyceride level by ApoE phenotype:a meta analysis,J Lipids Res ,1992,33:447-454

  21.Utermann G et al Apolipoprotein E polymorphism in health and disease Am Heart J,1987,113:433-440

  22.陈保生,等电点聚焦方法在AopE遗传表型研究中的应用,基础医学与临床,1991,11:57-60

  23.Zannis V,Just P,Breslow J,et al .Human apolipoprotein e isoprotein subclasses are genetiaclly determined Am J Hum Genet,1981,33:11-24

  24.Kurosaka D,Teramoto T,Matsushima T,et al .Apolipoprotein e deficiency with a depressed mRNA of mormal size .Atherosclerosis ,1991, 88:15-20

  25.Kamboh M,Eerrell R,Sepehrnia B,Genetic studies of human apolipoprotein Ⅳ:Structural heterogeneity of apolipoprotein H(β2-glycoprotein I),Am J,Hum Genet ,1988,42:452-457

  26.McNally T,Mackie I,Isenberg D et al.Immunoelectrophoresis and ELISA techniques for assay of plasma β2-glycoprotein –I and the influence of plasma lipids ,Thrombosis Research,1993,72:275-286

  27.McNeil H,Simpson R,Chesteman C,et al.Antiphospholipid antibodies are directed a complex antigen that in cludes a lipid binding inhibitor of coagulation: β2gycoprotein –I(apolipotprotein H)Proc Natl Acad Sci USA,1990,87:4120-4124

  28.Roberto G,Gianluca R,Maurizio Cet al.Apolipoprtein H:a two-step isolation method.J Lipid Res ,1996,37:902-904

  29.Siest G,Pillot T,Regis-Bailly A et al.Apolipoprotein E:An important gene and protein to follow in laboratory medicine Clin Chem,1995,41:1068-1086

  30.杨振华,夏永静译.载脂蛋白E:实验医学研究中的重要基因与蛋白质,交换资料,1995