Naturally occurring human plasminogen, like genetically related apolipoprotein(a), contains oxidized phosphatidylcholine adducts.
Naturally occurring human plasminogen, like genetically related apolipoprotein(a), contains oxidized phosphatidylcholine adducts.
复制标题
DOI：
10.1016/j.bbalip.2010.03.009
复制
发表时间：
2010-07
期刊：
影响因子：
--
通讯作者：
Scanu AM
中科院分区：
文献类型：
--
作者：
Edelstein C;Pfaffinger D;Yang M;Hill JS;Scanu AM
人载脂蛋白（a）（apo（a））在肝脏中合成，含有可能在肝脏部位产生的氧化磷脂酰胆碱（oxPtdPC）加合物。由于纤溶酶原（Plg）也在肝脏中合成，与载脂蛋白（a）具有遗传相关性和结构同源性，因此我们希望确定其是否含有oxPtdPC及其位置。我们使用从新鲜或冷冻的正常人血浆和几种商业制剂中分离的Plg。通过有机溶剂提取，一些游离的非共价结合的脂质。通过免疫印迹分析，所有产物均与T15反应，T15是一种对含磷酸胆碱的氧化磷脂（ox-PL）具有特异性的天然IgM单克隆抗体。这种免疫反应性保留在尿激酶型纤溶酶原激活剂产生的纤溶酶中，并在先前用脂蛋白相关磷脂酶A2（Lp-PLA 2）消化的Plg中被消除，该反应主要产生C16：0溶血磷脂酰胆碱物质，如通过质谱法测定的。Lp-PLA 2裂解与含赖氨酸的五肽化学连接的模型ox-PL后，也产生了Lysodeficients。从无机磷分析，我们发现2摩尔oxPtdPC/摩尔Plg分布在Kringles 1-4和mini-Plg结构域之间。OxPtdPC也存在于从培养的人HepG 2细胞的无血清培养基中分离的Plg中。总之，我们的研究结果提供了强有力的证据表明，天然存在的Plg含有oxPtdPC可能连接的席夫碱，也表明，链接发生在肝脏网站。鉴于oxPtdPCs的心血管致病性的新证据，我们推测它们可能在炎症条件下赋予Plg动脉粥样硬化血栓形成特性。
Human apolipoprotein(a) (apo(a)), synthesized in the liver, contains oxidized phosphatidylcholine (oxPtdPC) adducts probably generated at the hepatic site. Since plasminogen (Plg), also synthesized in the liver, is genetically related and structurally homologous to apo(a), we wanted to determine whether it contains oxPtdPCs and their location. We used Plg isolated from fresh or frozen normal human plasma and several commercial preparations. Some were freed of non-covalently bound lipids by organic solvent extraction. By immunoblot analyses all products reacted against T15, a natural IgM monoclonal antibody specific for phosphorylcholine -containing oxidized phospholipids (ox-PLs). This immunoreactivity was retained in urokinase type plasminogen activator -generated plasmin and was abrogated in Plg previously digested with lipoprotein-associated phospholipase A2 (Lp-PLA2), a reaction that generated that predominantly C16:0 lysophosphatidylcholine species as determined by mass spectrometry. Lysoderivatives were also generated upon the cleavage by Lp-PLA2 of a model ox-PL chemically linked to a lysine-containing pentapeptide. From inorganic phosphorous analyses, we found 2 moles of oxPtdPC/mole of Plg distributed between the kringles 1-4 and mini-Plg domain. OxPtdPCs were also present in the Plg isolated from the serum-free medium of cultured human HepG2 cells. In conclusion, our results provide strong evidence that naturally occurring Plg contains oxPtdPC probably linked by a Schiff base and also suggest that the linkage occurs at the hepatic site. Given the emerging evidence for the cardiovascular pathogenicity of oxPtdPCs we speculate that they may impart athero-thrombogenic properties to Plg under inflammatory conditions.
登录
查看更多内容
影响因子：
64.8
作者：
MCLEAN, JW;TOMLINSON, JE;LAWN, RM
通讯作者：
LAWN, RM
DOI：
10.1016/j.biocel.2008.11.002
发表时间：
2009-06
影响因子：
4
作者：
Ashraf, Mohammad Z.;Kar, Niladri S.;Podrez, Eugene A.
通讯作者：
Podrez, Eugene A.
影响因子：
56.9
作者：
DEUTSCH, DG;MERTZ, ET
通讯作者：
MERTZ, ET
影响因子：
4.8
作者：
Edelstein, Celina;Philips, Binu;Scanu, Angelo M.
通讯作者：
Scanu, Angelo M.
影响因子：
4.8
作者：
Friedman, P;Hörkkö, S;Dennis, EA
通讯作者：
Dennis, EA