Dissociation between activation of growth-related genes and mitogenic responses of neonatal vascular smooth muscle cells.

Dissociation between activation of growth-related genes and mitogenic responses of neonatal vascular smooth muscle cells.
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生长相关基因的激活与新生儿血管平滑肌细胞的有丝分裂反应之间的分离。

DOI:
10.1016/0006-291x(91)91235-5
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发表时间:
1991
影响因子:
3.1
通讯作者:
Ives,HE
Ives,HE
中科院分区:
生物学4区
文献类型:
--
作者:
Weiss,RH;Ives,HE

文献摘要

被引文献

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在新生儿血管平滑肌(VSM)细胞中,蛋白激酶C的激活可以阻断α-凝血酶对有丝分裂的反应。通过观察细胞周期中的早期转录事件,研究了这种生长抑制的分子机制。凝血酶和phorpol -12-肉豆蔻酸-13-乙酸酯(PMA)均诱导c-myconcogene mRNA表达;暴露于任何一种物质后4-5小时,表达水平达到峰值。当凝血酶和PMA同时加入时,c-myc的表达协同增加;蛋白激酶C的下调抑制了C -霉菌凝血酶的诱导。因此,在这些条件下,c-myc的表达与细胞生长成反比。凝血酶和PMA也在4-7h内诱导PDGF-A链mRNA的表达。对于c-myc,在PMA抑制凝血酶诱导的DNA合成的条件下,PMA和凝血酶协同增加PDGF a链的表达。因此,在pma介导的生长抑制过程中,有丝分裂和早期生长相关基因的表达是分离的。
In neonatal vascular smooth muscle (VSM) cells, activation of protein kinase C can block the mitogenic response to α-thrombin. The molecular mechanism for this growth inhibition was investigated by looking at early transcriptional events in the cell cycle. Both thrombin and phorbol-12-myristate-13-acetate (PMA) induced mRNA for the c-myconcogene; peak levels of expression were found 4–5 h after exposure to either agent. When thrombin and PMA were added together, c-mycexpression was increased synergistically; down-regulation of protein kinase C suppressed induction of c-mycby thrombin. Thus, c-mycexpression varied inversely with cell growth under these conditions. Thrombin and PMA also both induced expression of mRNA for the PDGF-A chain over 4–7h. As for c-myc, PMA and thrombin synergistically increased expression of the PDGF A-chain under conditions where PMA inhibits thrombin-induced DNA synthesis. Thus, mitogenesis and early growth-related gene expresion was dissociated during PMA-mediated growth inhibition.