Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells.
Lysophosphatidates bound to serum albumin activate membrane currents in Xenopus oocytes and neurite retraction in PC12 pheochromocytoma cells.
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DOI：
10.1016/s0021-9258(19)36618-9
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发表时间：
1992-10
期刊：
影响因子：
--
通讯作者：
Gabor Tigyi;Ricardo Miledi
中科院分区：
文献类型：
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作者：
Gabor Tigyi;Ricardo Miledi
血清中含有一种因子，可与白蛋白共同纯化，并引起PC 12细胞中的神经突收缩，在体外抑制肿瘤细胞的增殖，并激活爪蟾卵母细胞和其他细胞中的磷脂酰肌醇/Ca 2+第二信使系统。血清白蛋白的活性取决于与白蛋白结合的几种溶血磷脂。用甲醇从血清白蛋白中提取的脂质的薄层色谱分析显示了十几种成分，其中几种引起了卵母细胞中的振荡电流。与血清白蛋白相反，这些脂质中的大多数在血浆中不存在，其缺乏生物活性。最丰富的天然存在的活性成分被确定为硬脂酰溶血磷脂酸。合成制备的溶血磷脂再现了天然血清因子的生物活性。将合成溶血磷脂酸添加到不含脂肪酸的无活性白蛋白中，使白蛋白恢复活性，使活性因子对水性溶剂不可透析，并防止各种脂肪酶消化。由于生物活性溶血磷脂酸在血液凝固过程中产生，在血小板的存在下，溶血磷脂酸已被证明以前激活血小板，我们建议溶血磷脂酸可能发挥重要作用，连接血小板活化受体介导的组织再生。
Serum contains a factor that co-purifies with albumin and causes neurite retraction in PC12 cells, inhibits the proliferation of tumor cells in vitro, and activates the phosphatidylinositol/Ca2+ second messenger system in Xenopus oocytes and other cells. The activity of serum albumin depends on several lysophospholipids bound to albumin. Thin layer chromatographic analysis of the lipids extracted by methanol from serum albumin revealed over a dozen components, several of which evoked oscillatory currents in oocytes. In contrast to serum albumin, most of these lipids were absent in plasma, which lacks the biological activity. The most abundant naturally occurring active component was identified as stearoyl-lysophosphatidic acid. Synthetically prepared lysophosphatidates reproduced the biological activities of the natural serum factor. Adding synthetic lysophosphatidates to inactive fatty acid-free albumin restored activity to the albumin, making the active factor nondialyzable against aqueous solvents and protecting against digestion by various lipases. Since the biologically active lysophosphatidates were produced during blood clotting, in the presence of platelets, and lysophosphatidates have been shown previously to activate platelets, we propose that lysophosphatidates may play an important role in linking platelet activation to receptor-mediated tissue regeneration.