Role of mitogen-activated protein kinase in the angiotensin II-induced DNA synthesis in vascular smooth muscle cells.
Role of mitogen-activated protein kinase in the angiotensin II-induced DNA synthesis in vascular smooth muscle cells.
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丝裂原激活蛋白激酶在血管紧张素 II 诱导血管平滑肌细胞 DNA 合成中的作用。
DOI：
10.1161/01.hyp.31.5.1151
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发表时间：
1998
期刊：
影响因子：
8.3
通讯作者：
A. Sachinidis
中科院分区：
文献类型：
--
作者：
S. Seewald;C. Seul;Ralf Kettenhofen;D. Bokemeyer;Y. Ko;Hans Vetter;A. Sachinidis
丝裂原活化蛋白（MAP）激酶的激活和细胞内游离钙浓度（[Ca~（2+）] i）的增加进行了讨论，在参考不同的蛋白激酶的激活和血管平滑肌细胞（VSMCs）的生长。本研究旨在探讨血管紧张素II（Ang II）诱导的[Ca~（2+）] i升高对44-kD/42-kDMAP激酶（p44mapk/p42mapk）激活和DNA合成的作用。实验通过细胞内螯合剂1，2-二-（邻氨基-5-甲基苯氧基）乙烷-N，N，N ′，N ′-四乙酸四乙酰氧基甲酯（MAPTAM）螯合[Ca~（2+）]_i来进行。钙离子测定采用Fura 2法。MAP激酶活性通过蛋白质印迹法测定。通过测量[3H]胸苷掺入细胞DNA来确定DNA合成。用20 μ mol/L MAPTAM处理VSMCs 30分钟，10秒时血管紧张素II诱导的最大增加完全消失。Ang Ⅱ磷酸化p44mapk/p42mapk的作用呈时间依赖性，在3min时达到最大值。在MAPTAM处理的细胞中，MAP激酶亚型的最大磷酸化转移到5分钟，去磷酸化与未处理的细胞相比被延迟。与此结果一致，MAP激酶磷酸酶-1的诱导在MAPTAM处理的细胞中明显受损。在未处理的细胞中，Ang II诱导[3H]胸苷掺入DNA合成增加2.3倍。这种作用在MAPTAM处理的细胞中没有减少。PD98059（10 μ mol/L）对Ang Ⅱ诱导的MAP激酶活性抑制率为85%，但对Ang Ⅱ诱导的DNA合成无抑制作用。总之，血管紧张素II诱导的MAP激酶的刺激是一个Ca 2+依赖性的过程。此外，阻断Ang II诱导的早期细胞内事件的刺激，如[Ca 2 +] i增加或MAP激酶磷酸化，并不伴随着抑制Ang II诱导的DNA合成。
The activation of mitogen-activated protein (MAP) kinase and increase in intracellular free calcium concentration ([Ca2+]i) are discussed in reference to activation of different protein kinases and growth of vascular smooth muscle cells (VSMCs). The aim of the present study was to investigate the role of angiotensin (Ang) II-induced increase in [Ca2+]i for activation of 44-kD/42-kD MAP kinase (p44mapk/p42mapk) and DNA synthesis in VSMCs. Experiments were performed by chelation of [Ca2+]i by the intracellular chelator 1,2-bis-(o-amino-5-methylphenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxymethyl ester (MAPTAM). Ca2+ was measured by the fura 2 method. MAP kinase activation was determined by the Western blotting method. DNA synthesis was determined by measurement of [3H]thymidine incorporation into the cell DNA. Treatment of VSMCs with 20 micromol/L MAPTAM for 30 minutes resulted in a complete abolishment of the maximal Ang II-induced increase at 10 seconds. Ang II phosphorylated the p44mapk/p42mapk in a time-dependent manner, showing a maximum at 3 minutes. In MAPTAM-treated cells, the maximal phosphorylation of MAP kinase isoforms was shifted to 5 minutes, and dephosphorylation was delayed compared with untreated cells. In concordance with this finding, the induction of the MAP kinase phosphatase-1 was markedly impaired in MAPTAM-treated cells. Ang II induced a 2.3-fold increase in [3H]thymidine incorporation into DNA synthesis in untreated cells. This effect was not reduced in MAPTAM-treated cells. Treatment of the cells with PD 98059 (10 micromol/L), a MAP kinase kinase inhibitor, caused 85% inhibition of the Ang II-induced activation of MAP kinases but did not inhibit the Ang II-induced DNA synthesis. In conclusion, the Ang II-induced stimulation of the MAP kinase is a Ca2+-dependent process. Furthermore, blockade of the Ang II-induced stimulation of the early intracellular events, such as increase in [Ca2+]i or phosphorylation of the MAP kinase, is not accompanied by an inhibition of the Ang II-induced DNA synthesis.
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影响因子：
8.3
作者：
BERK, BC;VEKSHTEIN, V;TSUDA, T
通讯作者：
TSUDA, T
Ca2 在正常细胞和转化细胞中血清刺激的 Na 内流中的作用。
DOI：
10.1152/ajpcell.1985.248.3.c288
发表时间：
1985
期刊：
The American journal of physiology
影响因子：
--
作者：
Owen,NE;Villereal,ML
通讯作者：
Villereal,ML
影响因子：
20.1
作者：
Lucchesi, PA;Bell, JM;Berk, BC
通讯作者：
Berk, BC
血管紧张素 II 和精氨酸加压素诱导培养的大鼠主动脉平滑肌细胞中蛋白质合成和含量增加的机制。
影响因子：
20.1
作者：
Turla,MB;Thompson,MM;Corjay,MH;Owens,GK
通讯作者：
Owens,GK
抗高血压药物治疗对自发性高血压大鼠血管平滑肌细胞肥大、超倍体和增生的不同影响。
影响因子：
20.1
作者：
Owens,GK
通讯作者：
Owens,GK