Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.

Human platelet-derived growth factor stimulates prostaglandin synthesis by activation and by rapid de novo synthesis of cyclooxygenase.
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人血小板衍生生长因子通过环加氧酶的激活和快速从头合成来刺激前列腺素合成。

DOI:
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发表时间:
1985
影响因子:
15.9
通讯作者:
Ross
Ross
中科院分区:
医学1区
文献类型:
--
作者:
Andreas;J. Habenicht;M. Goerig;Jurgen Grulich;D. Rothe;R. Gronwald;U. Loth;G. Schettler;B. Kommerell;Russell;Ross

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人血小板源性生长因子 (PDGF) 在 Swiss 3T3 细胞的细胞周期中以两个不同的时间间隔刺激前列腺素 (PG) E2 合成,第一个平台期在添加 PDGF 后 10 分钟内,第二个平台期在 2-4 小时内。 4 小时时,PDGF 刺激的培养物中 PGE2 的浓度超过静止对照细胞的 10-15 倍。与高达 16 µM 的外源花生四烯酸 (AA) 一起孵育的静止细胞仅合成少量的 PGE2。相反,添加 PDGF 4 小时后,由外源 AA 合成的 PGE2 浓度超过静止培养物中的浓度 28 倍。如使用 [14C]AA 的实验所示,PDGF 刺激对外源 AA PG 合成的影响不能用生长因子介导的细胞游离 AA 池增加来解释。 PDGF 还刺激外源 AA 合成 PGI2(前列环素)、血栓素和 PGF2 α。虽然10微克/毫升放线菌酮抑制蛋白质合成对PGE2合成的早期增加没有影响,但完全阻止了第二次增加。此外,PDGF 刺激后 6 小时放线菌酮处理导致外源 AA 的 PGE2 合成迅速下降。用 100 microM 阿司匹林预处理并用 PDGF 刺激的静止培养物随后在 180 分钟内从环氧合酶抑制中恢复。我们的结果表明,磷脂酶激活和由此产生的 AA 释放不足以诱导 PDGF 刺激细胞中观察到的 PG 合成爆发。相反,PDGF 通过直接作用于 PG 合成酶系统来刺激 PG 合成,其中一种涉及不依赖于蛋白质合成的机制,另一种则需要环氧合酶的快速翻译。
Human platelet-derived growth factor (PDGF) stimulated prostaglandin (PG) E2 synthesis in the cell cycle of Swiss 3T3 cells at two distinct time intervals, with a first plateau within 10 min and a second plateau within 2-4 h after addition of PDGF. At 4 h, the concentration of PGE2 in PDGF-stimulated cultures exceeded the quiescent control cells by a factor of 10-15. Quiescent cells incubated with up to 16 microM exogenous arachidonic acid (AA) synthesized only small amounts of PGE2. In contrast, 4 h after addition of PDGF, the concentration of PGE2 synthesized from exogenous AA exceeded that in quiescent cultures by a factor of 28. The effect of PDGF stimulation on PG synthesis from exogenous AA could not be explained by growth factor-mediated increase in the cellular free AA pool as shown in experiments using [14C]AA. PDGF also stimulated synthesis of PGI2 (prostacyclin), thromboxane, and PGF2 alpha from exogenous AA. While inhibition of protein synthesis by 10 micrograms/ml cycloheximide had no effect on the early increase in PGE2 synthesis, the second increase was completely prevented. Additionally, cycloheximide treatment at 6 h after PDGF stimulation resulted in rapid decline of PGE2 synthesis from exogenous AA. Quiescent cultures pretreated with 100 microM aspirin and stimulated by PDGF thereafter recovered from cyclooxygenase inhibition within 180 min. Our results suggest that phospholipase activation and resultant AA release is not sufficient to induce the burst of PG synthesis observed in PDGF-stimulated cells. Instead, PDGF stimulates PG synthesis by direct effects on the PG-synthesizing enzyme system, one involving a protein synthesis-independent mechanism and another that requires rapid translation of cyclooxygenase.
血小板摄取和释放花生四烯酸。
DOI: --
发表时间: 1983
期刊: Advances in prostaglandin, thromboxane, and leukotriene research
影响因子: --
作者:
Majerus,PW;Prescott,SM;Hofmann,SL;Neufeld,EJ;Wilson,DB
通讯作者: Wilson,DB