Src tyrosine kinases and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases mediate pressure-induced c-fos expression in cannulated rat mesenteric small arteries.
Src tyrosine kinases and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases mediate pressure-induced c-fos expression in cannulated rat mesenteric small arteries.
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Src 酪氨酸激酶和细胞外信号调节激酶 1/2 丝裂原激活蛋白激酶介导插管大鼠肠系膜小动脉中压力诱导的 c-fos 表达。
DOI：
10.1161/01.hyp.37.3.955
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Prewitt,RL
中科院分区：
文献类型：
--
作者：
Wesselman,JP;Dobrian,AD;Schriver,SD;Prewitt,RL
慢性高血压与小动脉重塑有关。有证据表明，高压本身可能导致这些结构变化，但负责的机制并不清楚。以前，我们表明，压力诱导的c-fos在完整的大鼠肠系膜小动脉插管表达抑制染料木素，一般酪氨酸激酶抑制剂。本研究的目的是进一步揭示潜在的信号转导机制，我们特别测试了src酪氨酸激酶和细胞外信号调节激酶（ERK）的参与。将大鼠肠系膜小动脉插管于双血管室中。在60分钟的平衡期后，一条动脉中的压力增加到140 mm Hg，而另一条动脉保持在90 mm Hg。半定量逆转录-聚合酶链反应用于测定c-fos表达，Western blotting用于检测ERK磷酸化水平。在抑制剂除莠霉素A（1 μmol/L）、PP 1（10 μmol/L）、PP 2（10 μ mol/L）和PD 98059（30 μmol/L）的作用下检测src和ERK的参与。暴露于140 mm Hg一小时使c-fos/亲环蛋白比率增加3.6倍，从0.29±0.07增加到1.06±0.25。所有受试抑制剂均抑制压力诱导的c-fos表达增加。暴露于140 mm Hg 5分钟增加ERK磷酸化，并且在PP 1存在下被消除。结果表明，压力诱导的c-fos表达在完整的大鼠肠系膜小动脉插管可能是介导的，至少部分，由src酪氨酸激酶和ERK。
Chronic hypertension is associated with remodeling of small arteries. There is evidence that the high pressure itself may cause these structural changes, but the responsible mechanisms are not clearly defined. Previously we showed that pressure-induced c-fos expression in intact cannulated rat mesenteric small arteries was inhibited by genistein, a general tyrosine kinase inhibitor. The purpose of this study was to further unravel the underlying signal transduction mechanisms, and we particularly tested the involvement of src tyrosine kinases and extracellular signal–regulated kinase (ERK). Rat mesenteric small arteries were cannulated in a dual-vessel chamber. After a 60-minute equilibration period, the pressure in 1 artery was increased to 140 mm Hg, while the other artery remained at 90 mm Hg. Semiquantitative reverse transcriptase–polymerase chain reaction was used to determine c-fos expression, and Western blotting was used to examine levels of ERK phosphorylation. The involvement of src and ERK was tested with the inhibitors herbimycin A (1 μmol/L), PP1 (10 μmol/L), PP2 (10 μmol/L), and PD98059 (30 μmol/L). One-hour exposure to 140 mm Hg increased the c-fos/cyclophilin ratio 3.6-fold, from 0.29±0.07 to 1.06±0.25. All the tested inhibitors suppressed the pressure-induced increase of c-fos expression. A 5-minute exposure period to 140 mm Hg increased ERK phosphorylation, and this was abolished in the presence of PP1. The results suggest that pressure-induced c-fos expression in intact cannulated rat mesenteric small arteries may be mediated, at least in part, by src tyrosine kinases and ERK.