Zhou Z, Luchoomun J, Bakillah A, Hussain M M
Department of Pathology, The Allegheny University of the Health Sciences, MCP Hahnemann School of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Biochim Biophys Acta. 1998 Mar 6;1391(1):13-24. doi: 10.1016/s0005-2760(97)00200-2.
Free fatty acids and lysophosphatidylcholine (lysoPC) are the major lipids bound to human plasma albumin. The effects of fatty acids on the hepatic production of Apolipoprotein B (apo B) have been studied but those of lysoPC have not. In HepG2 cells, lysoPC increased apo B secretion in different experiments by 50-120%, but did not affect the flotation properties of secreted lipoproteins. LysoPC affected neither the cellular protein levels nor apo A-I secretion suggesting that its effect was specific to apo B. Apo B secretion was maximum after incubating cells for 6 h with 0.2 mM lysoPC as equimolar fatty acid free bovine serum albumin (BSA) complexes. LysoPC was metabolized by cells and its fatty acids were used for the synthesis of phosphatidylcholine and triglycerides (TG). Experiments were performed to understand the mechanism of lysoPC action. LysoPC increased the incorporation of 3H-glycerol into newly synthesized cellular (3-fold) and secreted (4-fold) triglycerides, and increased the synthesis (40%) and secretion (4-fold) of phospholipids. LysoPC did not affect apo B synthesis, but inhibited the intracellular degradation of apo B and increased its secretion. Triacsin C (5 microM), an inhibitor of long chain acyl-CoA synthase, completely inhibited the induction of lipid synthesis and abolished the effect of lysoPC on apo B secretion. These studies indicated that lysoPC increased apo B secretion by inducing lipid synthesis; newly synthesized lipids probably protected apo B from intracellular degradation and enhanced secretion. These studies are consistent with the hypothesis that physiologic concentrations of lysoPC can be an important modulator for hepatic apo B secretion.
游离脂肪酸和溶血磷脂酰胆碱（lysoPC）是与人类血浆白蛋白结合的主要脂质。脂肪酸对载脂蛋白B（apo B）肝脏生成的影响已得到研究，但lysoPC的影响尚未研究。在HepG2细胞中，在不同实验中lysoPC使apo B分泌增加了50%-120%，但不影响分泌型脂蛋白的漂浮特性。lysoPC既不影响细胞蛋白水平，也不影响apo A-I分泌，表明其作用对apo B具有特异性。用0.2 mM lysoPC作为等摩尔无脂肪酸牛血清白蛋白（BSA）复合物孵育细胞6小时后，apo B分泌达到最大值。lysoPC被细胞代谢，其脂肪酸用于磷脂酰胆碱和甘油三酯（TG）的合成。进行实验以了解lysoPC的作用机制。lysoPC使3H-甘油掺入新合成的细胞内甘油三酯（3倍）和分泌的甘油三酯（4倍）增加，并增加磷脂的合成（40%）和分泌（4倍）。lysoPC不影响apo B合成，但抑制apo B的细胞内降解并增加其分泌。长链酰基辅酶A合酶抑制剂三辛素C（5 microM）完全抑制脂质合成的诱导，并消除lysoPC对apo B分泌的影响。这些研究表明，lysoPC通过诱导脂质合成增加apo B分泌；新合成的脂质可能保护apo B免受细胞内降解并增强分泌。这些研究与以下假设一致，即生理浓度的lysoPC可能是肝脏apo B分泌的重要调节剂。
