Cholesteryl ester transfer protein and phospholipid transfer protein have nonoverlapping functions in vivo
Cholesteryl ester transfer protein and phospholipid transfer protein have nonoverlapping functions in vivo
复制标题
DOI：
10.1074/jbc.m003523200
复制
发表时间：
2000-09-22
影响因子：
4.8
通讯作者：
Jiang, XC
中科院分区：
文献类型：
--
作者：
Kawano, K;Qin, SC;Jiang, XC
血浆磷脂转移蛋白（PLTP）和胆固醇酯转移蛋白（CETP）是介导血浆脂蛋白之间中性脂质和磷脂交换的同源分子。生化实验表明，只有CETP可以转移中性脂质，但PLTP和CETP转移或交换磷脂的能力可能存在重叠。最近开发的PLTP基因敲除（PLTP 0）小鼠具有完全缺乏的血浆磷脂转移活性和显著降低的高密度脂蛋白（HDL）水平。为了观察CETP是否可以在体内补偿PLTP缺陷，我们将CETP转基因（CETPTg）培育到PLTP 0背景中。使用体内试验测量[H-3]PC从VLDL转移到HDL或体外试验测定[H-3] PC从囊泡转移到HDL，我们在PLTP 0或CETPTg/PLTP 0小鼠中均未检测到磷脂转移活性。在普通饮食中，CETPTg/PLTP 0小鼠中的HDL-PL、HDL-CE和HDL-载脂蛋白Al显著低于PLTP 0小鼠（分别为45 +/- 7对79 +/- 9 mg/dl; 9 +/- 2对16 +/- 5 mg/dl;和51 +/- 6对100 +/- 9，任意单位）。在高脂肪、高胆固醇饮食中也得到了类似的结果。这些结果表明1）PLTP和CETP在体内的功能中没有冗余，和2）CETP转基因与PLTP缺陷的组合导致HDL水平的累加性降低，表明人PLTP缺陷状态的表型将包括降低的HDL水平。
Plasma phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are homologous molecules that mediate neutral lipid and phospholipid exchange between plasma lipoproteins, Biochemical experiments suggest that only CETP can transfer neutral lipids but that there could be overlap in the ability of PLTP and CETP to transfer or exchange phospholipids. Recently developed PLTP gene knock-out (PLTP0) mice have complete deficiency of plasma phospholipid transfer activity and markedly reduced high density lipoprotein (HDL) levels. To see whether CETP can compensate for PLTP deficiency in vivo, we bred the CETP transgene (CETPTg) into the PLTP0 background. Using an in vivo assay to measure the transfer of [H-3]PC from VLDL into HDL or an in vitro assay that determined [H-3]PC transfer from vesicles into HDL, we could detect no phospholipid transfer activity in either PLTP0 or CETPTg/PLTP0 mice. On a chow diet, HDL-PL, HDL-CE, and HDL-apolipoprotein Al in CETPTg/PLTP0 mice were significantly lower than in PLTP0 mice (45 +/- 7 versus 79 +/- 9 mg/dl; 9 +/- 2 versus 16 +/- 5 mg/dl; and 51 +/- 6 versus 100 +/- 9, arbitrary units, respectively). Similar results were obtained on a high fat, high cholesterol diet. These results indicate 1) that there is no redundancy in function of PLTP and CETP in vivo and 2) that the combination of the CETP transgene with PLTP deficiency results in an additive lowering of HDL levels, suggesting that the phenotype of a human PLTP deficiency state would include reduced HDL levels.