Potentiation of arachidonic acid release by phorbol myristate acetate in platelets is not due to inhibition of arachidonic acid uptake or incorporation into phospholipids.
Potentiation of arachidonic acid release by phorbol myristate acetate in platelets is not due to inhibition of arachidonic acid uptake or incorporation into phospholipids.
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佛波醇肉豆蔻酸酯乙酸酯在血小板中增强花生四烯酸的释放并不是由于抑制花生四烯酸的摄取或掺入磷脂。
DOI：
10.1016/0167-4889(91)90230-u
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Feinstein,MB
中科院分区：
文献类型：
--
作者：
Banga,HS;Halenda,SP;Feinstein,MB
蛋白激酶C的激活剂，如促进肿瘤的酚酯（如肉豆蔻酸酯）、甲萘醌、(−)-吲哚内酰胺V和1-油基2-乙酰甘油，通过离子载体提高细胞内Ca2+引起花生四烯酸的释放。蛋白激酶c激活剂的这种作用需要蛋白磷酸化，并归因于磷脂酶A2对磷脂的水解增强（Halenda, et al. (1989) Biochemistry 28, 7356-7363）。最近Fuse等人（1989）。医学杂志。化学。264,3890-3895)报道了花生四烯酸释放的明显增强实际上是由于抑制了释放的花生四烯酸的再摄取和再酯化过程。他们将其归因于花生四烯酰基辅酶a合成酶和花生四烯酰基辅酶a溶血磷脂酰基转移酶活性的丧失，这是在从肉豆酸酯处理的血小板中获得的膜中测量的。在本文中，我们发现肉豆蔻酸酯在强烈促进花生四烯酸释放的浓度下，既不抑制花生四烯酸进入血小板的吸收，也不抑制其与特定磷脂的结合。此外，脂肪酸8,11,14-二十碳四烯酸是花生四烯酰基辅酶a合成酶的竞争性底物，完全阻断花生四烯酸进入血小板，但与肉豆蔻酸酯酯不同，它不会增强Ca2+离子载体释放花生四烯酸。由此得出肉豆蔻酸酯佛波酯的作用是促进磷脂酶A2释放花生四烯酸的过程。
Activators of protein kinase C, such as tumor-promoting phorbol esters (e.g., phorbol myristate acetate), mezerein, (−)-indolactam V and 1-oleoyl 2-acetoyl glycerol, potentiate arachidonic acid release caused by elevation of intracellular Ca2+with ionophores. This action of protein kinase C-activators required protein phosphorylation, and was attributed to enhanced hydrolysis of phospholipids by phospholipase A2(Halenda, et al. (1989) Biochemistry 28, 7356–7363). Recently Fuse et al. ((1989)J. Biol. Chem. 264, 3890–3895) reported that the apparent enhanced release of arachidonate was actually due to inhibition of the processes of re-uptake and re-esterification of released arachidonic acid. They attributed this to loss of arachidonyl-CoA synthetase and arachidonyl-CoA lysophosphatide acyltransferase activities, which were measured in membranes obtained from phorbol myristate acetate-treated platelets. In this paper, we show that phorbol myristate acetate, at concentrations that strongly potontiate arachidonic acid release, does not inhibit either arachidonic acid uptake into platelets or its incorporation into specific phospholipids. Furthermore, the fatty acid 8,11,14-eicosatrionoic acid, a competitive substrate for arachidonyl-CoA synthetase, totally blocks arachidonic acid uptake into platelets, but, unlike phorbol myristate acetate, does not potentiate arachidonic acid release by Ca2+ionophores. We conclude that the action of phorbol myristate acetate is to promote the process of arachidonic acid release by phospholipase A2.