Enhancement of endogenous production of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor.
Enhancement of endogenous production of 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid in aortic smooth muscle cells by platelet-derived growth factor.
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血小板衍生生长因子增强主动脉平滑肌细胞中 12-L-羟基-5,8,10,14-二十碳四烯酸的内源性产生。
DOI：
10.1016/0024-3205(85)90083-9
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发表时间：
1985
期刊：
影响因子：
6.1
通讯作者：
W. Chang
中科院分区：
文献类型：
--
作者：
J. Nakao;Y. Koshihara;H. Ito;S. Murota;W. Chang
血小板源性生长因子（PDGF）对平滑肌细胞具有趋化作用，这种趋化作用可被脂氧合酶抑制剂咖啡酸抑制。为了研究花生四烯酸的内源性脂氧合酶产物对PDGF的趋化作用的作用，检测了PDGF对平滑肌细胞中脂氧合酶途径的影响。通过高效液相色谱法分析脂氧合酶产物。15-，5-和12-脂氧合酶的活动，在数量级，发现在平滑肌细胞匀浆。然而，当脂氧合酶的产品进行了分析，使用完整的细胞预标记[14 C]花生四烯酸，只有12-L-羟基-5，8，10，14-二十碳四烯酸（HETE）被发现是内源性产生。此外，12-HETE未释放到培养基中。用PDGF处理细胞增加了12-HETE的内源性产生。当每个时间点的对照值被认为是100%时，PDGF处理的细胞中的细胞内12-HETE的量在PDGF处理开始后1、3和10小时分别为126、132和146%。咖啡酸（10− 4 M）完全抑制PDGF对12-HETE产生的作用。然而，PDGF治疗没有显着改变12-脂氧合酶活性。这些结果表明PDGF对12-HETE产生的刺激作用不是由12-脂氧合酶活性的激活介导的。由于12-HETE本身是一种有效的平滑肌细胞的化学引诱剂，目前的数据强烈表明，12-HETE可能是一个重要的细胞内介质的PDGF对主动脉平滑肌细胞的趋化作用。
Platelet-derived growth factor (PDGF) has a chemotactic effect on smooth muscle cells, which is inhibited by lipoxygenase inhibitor caffeic acid. In order to study the role of endogenous lipoxygenase products of arachidonic acid on the chemotactic action of PDGF, effects of PDGF on the lipoxygenase pathway in smooth muscle cells were examined. Lipoxygenase products were analyzed by high-performance liquid chromatography. 15-, 5- and 12-lipoxygenase activities, in order of magnitude, were found in smooth muscle cell homogenate. However, when the lipoxygenase products were analyzed using intact cells prelabelled with [14C] arachidonic acid, only 12-L-hydroxy-5, 8, 10, 14-eicosatetraenoic acid (HETE) was found to be produced endogenously. In addition, 12-HETE was not released into the medium. Treatment of the cells with PDGF increased the endogenous production of 12-HETE. The amounts of intracellular 12-HETE in PDGF-treated cells were 126, 132 and 146% at 1,3, and 10 hr's after the initiation of PDGF treatment, respectively, when control value at each time point was considered as 100%. Caffeic acid (10−4M) completely inhibited the PDGF effect on 12-HETE production. However, PDGF treatment did not significantly alter the 12-lipoxygenase activity. These results suggest that the stimulatory effect of PDGF on 12-HETE production was not mediated by the activation of 12-lipoxygenase activity. Since 12-HETE itself is a potent chemoattractant for smooth muscle cells, the present data strongly suggest that 12-HETE could be an important intracellular mediator of the chemotactic action of PDGF on aortic smooth muscle cells.