Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells.
Modulation of the erythropoietin-induced proliferative pathway by cAMP in vascular smooth muscle cells.
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cAMP 对血管平滑肌细胞中促红细胞生成素诱导的增殖途径的调节。
DOI：
10.1152/ajpcell.00143.2002
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Y. Asano
中科院分区：
文献类型：
--
作者：
C. Ito;E. Kusano;Y. Furukawa;Hisashi Yamamoto;Shin;T. Akimoto;O. Iimura;Y. Ando;Y. Asano
我们之前报道过促红细胞生成素（Epo）对大鼠血管平滑肌细胞（VSMC）具有促丝分裂作用，而促丝分裂原激活蛋白激酶（MAPK）级联的激活是Epo诱导的有丝分裂发生的重要介质。细胞内cAMP的增加对VSMC具有抗增殖作用。因此，我们假设cAMP效应物抑制epo诱导的大鼠VSMC中MAPK的激活。当我们将VSMC暴露于重组人Epo （rHuEpo）中时，DNA合成增加。福斯克林（Fsk）或西洛他唑（Cil）降低rHuEpo刺激的DNA合成。与rp - camp三乙胺共孵育消除了Fsk对DNA合成和MAPK活性的抑制。rHuEpo和phorbol 12-肉豆蔻酸酯13-乙酸都上调了MEK和MAPK的磷酸化。Fsk预处理抑制了这些磷酸化。蛋白激酶C抑制剂也抑制MEK和MAPK的磷酸化。此外，Fsk诱导Raf-1丝氨酸-259位点磷酸化。这些结果表明，cAMP抑制epo诱导的MAPK激活，这种抑制可能在上游或Raf-1处受到调节。结果还表明，这些可积累cAMP的药物可能对epo刺激的直接作用具有保护作用。
We previously reported that erythropoietin (Epo) has a mitogenic effect on rat vascular smooth muscle cells (VSMC) and that activation of the mitogen-activated protein kinase (MAPK) cascade is an important mediator for Epo-induced mitogenesis. An increase in intracellular cAMP has an antiproliferative effect on VSMC. We therefore hypothesized that cAMP effectors inhibit Epo-induced MAPK activation in rat VSMC. When we exposed VSMC to recombinant human Epo (rHuEpo), DNA synthesis was increased. Forskolin (Fsk) or cilostazol (Cil) decreased the DNA synthesis stimulated by rHuEpo. Coincubation with Rp-cAMPS triethylamine canceled the suppression of DNA synthesis and MAPK activity by Fsk. Both rHuEpo and phorbol 12-myristate 13-acetate upregulated phosphorylations of MEK and MAPK. Pretreatment with Fsk inhibited these phosphorylations. Protein kinase C inhibitors also suppressed MEK and MAPK phosphorylations. Moreover, Fsk induced phosphorylation of Raf-1 at serine-259. These results indicated that cAMP inhibited Epo-induced MAPK activation and that this suppression might be regulated upstream or at Raf-1. The results also suggested that these agents, which could accumulate cAMP, might be protective for Epo-stimulated direct action.
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促红细胞生成素诱导 Raf-1 激活，而 Raf-1 是促红细胞生成素介导的增殖所必需的。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Carroll,MP;Spivak,JL;McMahon,M;Weich,N;Rapp,UR;May,WS
通讯作者：
May,WS
影响因子：
4.1
作者：
Weber, JD;Raben, DM;Baldassare, JJ
通讯作者：
Baldassare, JJ
DOI：
--
发表时间：
1993-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. Morrison;G. Heidecker;U. Rapp;T. Copeland
通讯作者：
D. Morrison;G. Heidecker;U. Rapp;T. Copeland
影响因子：
20.1
作者：
Lucchesi, PA;Bell, JM;Berk, BC
通讯作者：
Berk, BC
百日咳毒素敏感的三磷酸鸟苷结合蛋白在成红细胞对促红细胞生成素反应中的作用。
影响因子：
20.3
作者：
Miller,BA;Foster,K;Robishaw,JD;Whitfield,CF;Bell,L;Cheung,JY
通讯作者：
Cheung,JY