首页> 外文期刊>American Journal of Physiology >Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells.
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Cigarette smoke extract induces endothelin-1 via protein kinase C in pulmonary artery endothelial cells.

机译:香烟烟雾提取物通过肺动脉内皮细胞中的蛋白激酶C诱导内皮素-1。

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摘要

We examined the mechanism of endothelin (ET)-1 regulation by cigarette smoke extract (CSE) and the effect of platelets on CSE-induced stimulation of ET-1 gene expression in human and bovine pulmonary artery endothelial cells (PAECs). Our data show that CSE (1%) induces ET-1 gene expression (after 1 h) and ET-1 peptide synthesis (after 4 h) in bovine PAECs. The induction of preproET-1 mRNA level was due to de novo transcription, and new protein synthesis was not required for this induction. The protein kinase C inhibitors staurosporine (10(-8) mol/l) and calphostin C (10(-7) mol/l) abolished the induction of ET-1 gene expression by CSE in bovine and human PAECs. Although a lower concentration of platelets (10(6) cells/ml in bovine PAECs; 10(7) cells/ml in human PAECs) did not significantly alter ET-1 gene expression in PAECs, incubation of platelets with CSE (1%) and PAECs produced a significant increase in preproET-1 mRNA and ET-1 peptide compared with the values in the presence of CSE (1%) alone. CSE (1%) induced platelet aggregation and increased the expression of platelet membrane glycoproteins ex vivo. Thus our data suggest that CSE stimulates ET-1 gene expression via PKC in PAECs. CSE and platelets showed a synergistic effect on ET-1 gene expression, possibly through the activation of platelets by CSE.
机译:我们检查了香烟烟雾提取物(CSE)调节内皮素(ET)-1的机制以及血小板对CSE诱导的人和牛肺动脉内皮细胞(PAECs)ET-1基因表达的刺激作用。我们的数据表明,CSE(1%)在牛PAEC中诱导ET-1基因表达(1小时后)和ET-1肽合成(4小时后)。 preproET-1 mRNA水平的诱导归因于从头转录,并且该诱导不需要新的蛋白质合成。蛋白激酶C抑制剂星形孢菌素(10(-8)mol / l)和钙磷蛋白C(10(-7)mol / l)取消了CSE在牛和人PAEC中对ET-1基因表达的诱导。尽管较低的血小板浓度(牛PAEC中为10(6)个细胞/ ml;人PAEC中为10(7)个细胞/ ml)不会显着改变PAECs中的ET-1基因表达,但将血小板与CSE孵育(1%)与单独存在CSE(1%)时的值相比,PAECs和PAECs显着增加了preproET-1 mRNA和ET-1肽。 CSE(1%)诱导血小板聚集并增加离体血小板膜糖蛋白的表达。因此,我们的数据表明,CSE通过PAEC中的PKC刺激ET-1基因表达。 CSE和血小板可能通过CSE激活血小板而对ET-1基因表达产生协同作用。

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