Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells
Phospholipase D mediates matrix metalloproteinase-9 secretion in phorbol ester-stimulated human fibrosarcoma cells
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DOI：
10.1074/jbc.274.2.735
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发表时间：
1999-01-08
影响因子：
4.8
通讯作者：
Exton, JH
中科院分区：
文献类型：
--
作者：
Williger, BT;Ho, WT;Exton, JH
磷脂酶D(PLD)与高尔基体的囊泡运输有关，因此与细胞分泌有关。在本研究中，我们发现佛波醇12-肉豆蔻酸酯13-乙酸酯以时间和剂量依赖的方式刺激HT1080人纤维肉瘤细胞分泌基质金属蛋白酶-9，其中包括蛋白激酶C。佛波酯还增加了细胞内PLD的活性。通过观察短链磷脂酸(PA)对基质金属蛋白酶-9(MMP9)分泌的刺激作用，以及用短链二酰甘油抑制正丙醇对MMP9分泌的抑制，提供了PLD参与刺激MMP9分泌的证据。我们排除了MMP9的分泌是由PA经磷脂酸磷酸酶生成的二酰甘油诱导的可能性。此外，该酶的抑制剂普萘洛尔对佛波醇12-肉豆蔻酸酯13-醋酸酯或PA诱导的分泌均无影响。这些数据表明，蛋白激酶C的激活增加了HT1080细胞的基质金属蛋白酶-9的分泌，并与PLD和PA的形成有关。
Phospholipase D (PLD) has been implicated in vesicle trafficking in the Golgi and hence secretion. In this study, we show that the secretion of matrix metalloproteinase-9 (MMP-9) from HT 1080 human fibrosarcoma cells was stimulated by phorbol 12-myristate 13-acetate in a time- and dose dependent manner that involved protein kinase C. The phorbol ester also increased PLD activity in the cells. Evidence that PLD was involved in the stimulation of MMP-9 secretion was provided by the observations that the secretion of MMP-9 was stimulated by the introduction of short-chain phosphatidic acid (PA) into the growth medium and that inhibition of PA production by 1-propanol inhibited secretion, Using a short-chain diacylglycerol we excluded the possibility that MMP-9 secretion was induced by diacylglycerol formed from PA by phosphatidic acid phosphatase. Furthermore, propranolol, an inhibitor of this enzyme, had no effect on secretion induced by either phorbol 12-myristate 13-acetate or PA. The data presented here indicate that activation of protein kinase C increases MMP-9 secretion in HT 1080 cells and implicate PLD and PA formation in the effect.