FUNCTIONAL EXPRESSION OF HUMAN AND MOUSE PLASMA PHOSPHOLIPID TRANSFER PROTEIN - EFFECT OF RECOMBINANT AND PLASMA PLTP ON HDL SUBSPECIES

FUNCTIONAL EXPRESSION OF HUMAN AND MOUSE PLASMA PHOSPHOLIPID TRANSFER PROTEIN - EFFECT OF RECOMBINANT AND PLASMA PLTP ON HDL SUBSPECIES
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DOI:
10.1016/0005-2760(95)00091-p
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发表时间:
1995-08-24
期刊:
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子:
--
通讯作者:
TU, AY
TU, AY
中科院分区:
其他
文献类型:
--
作者:
ALBERS, JJ;WOLFBAUER, G;TU, AY

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本文介绍了小鼠血浆磷脂转移蛋白(PLTP)的分子克隆和小鼠与人PLTP互补DNA的真核细胞表达。小鼠PLTP与人类PLTP有83%的氨基酸序列相同。PLTP在幼鼠肾细胞中产生。表达PLTP的BHK细胞条件培养基具有磷脂转移活性和高密度脂蛋白(HDL)转化活性。Northern blot检测的16个人体组织中均检测到PLTP mRNA,其中卵巢、胸腺和胎盘的水平最高。在8个小鼠组织中也检测了PLTP mRNA,其中肺、脑和心脏的PLTP mRNA水平最高。研究了纯化的人血浆源性PLTP和重组人PLTP (rPLTP)对人血浆HDL亚种Lp(A-I)和Lp(A-I/A-II)的影响。等离子体PLTP或rPLTP将Lp(a - i)的两个不同大小的亚种转化为大种、中间种和小种。Lp(A-I/A-II)颗粒在等离子体或rPLTP的作用下,具有多个大小亚种的Lp(A-I/A-II)颗粒发生了显著变化,最大但不太突出的亚种成为优势亚种,最小的亚种浓度增加。因此,PLTP促进了Lp(A-I)和Lp(A-I/A-II)向较大和较小颗粒群体的转化。此外,人类PLTP和小鼠rPLTP都能够将人类或小鼠HDL转化为更大或更小的颗粒。这些观察结果表明,PLTP可能在细胞外磷脂转运和HDL颗粒调节中发挥关键作用。
The molecular cloning of mouse plasma phospholipid transfer protein (PLTP) and the eukaryotic cell expression of complementary DNA for mouse and human PLTP are described. Mouse PLTP was found to share 83% amino acid sequence identity with human PLTP. PLTP was produced in baby hamster kidney cells. Conditioned medium from BHK cells expressing PLTP possessed both phospholipid transfer activity and high density lipoprotein (HDL) conversion activity. PLTP mRNA was detected in all 16 human tissues examined by Northern blot analysis with the ovary, thymus, and placenta having the highest levels. PLTP mRNA was also examined in eight mouse tissues with the highest PLTP mRNA levels found in the lung, brain, and heart. The effect of purified human plasma-derived PLTP and human recombinant PLTP (rPLTP) on the two human plasma HDL subspecies Lp(A-I) and Lp(A-I/A-II) was evaluated. Plasma PLTP or rPLTP converted the two distinct size subspecies of Lp(A-I) into a larger species, an intermediate species, and a smaller species. Lp(A-I/A-II) particles containing multiple size subspecies were significantly altered by incubation with either plasma or rPLTP with the largest but less prominent subspecies becoming the predominant one, and the smallest subspecies increasing in concentration. Thus, PLTP promoted the conversion of both Lp(A-I) and Lp(A-I/A-II) to populations of larger and smaller particles. Also, both human PLTP and mouse rPLTP were able to convert human or mouse HDL into larger and smaller particles. These observations suggest that PLTP may play a key role in extracellular phospholipid transport and modulation of HDL particles.