Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats
Characterization of activation of MAP kinase superfamily in vasculature from diabetic rats
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DOI：
10.5551/jat.e514
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Tominaga, Makoto
中科院分区：
文献类型：
--
作者：
Igarashi, Masahiko;Hirata, Akihiko;Tominaga, Makoto
目的：本研究旨在探讨丝裂原活化蛋白（MAP）激酶超家族在糖尿病中的激活机制，并从大鼠血管平滑肌细胞（VSMCs）中观察MAP激酶超家族的激活情况。结果：糖尿病大鼠胸主动脉中细胞外信号调节蛋白激酶（ERK）-1、c-jun氨基末端蛋白激酶（JNK）-1、-2和p38蛋白表达均较正常大鼠显著增加。相反，ERK-1和-2，JNK-1和p38的磷酸化蛋白水平在糖尿病大鼠中比在正常大鼠中显著升高。在正常大鼠的VSMCs中，高浓度葡萄糖培养3天显著增加ERK和p38的磷酸化蛋白水平，但不增加JNKs，而这些蛋白水平没有任何变化。糖尿病大鼠血清IL-1 β水平明显高于正常大鼠。几种类型的促炎细胞因子剂量依赖性磷酸化的水平的ERK，JNK-1，和p38，但不是JNK-2，在正常大鼠的VSMCs。在糖尿病大鼠的细胞中，ERK和p38的磷酸化蛋白水平被IL-1 β显著升高。此外，干扰素-γ磷酸化水平的ERK在糖尿病细胞比在正常cells.Conclusion：我们的研究结果表明，在糖尿病条件下，MAP激酶超家族被激活的不同途径在血管，即，ERK和p38可能主要被高浓度葡萄糖和几种促炎细胞因子的复合物磷酸化，但JNK-1的磷酸化可能取决于促炎细胞因子如IL-1 β和/或除葡萄糖外的其他未知因子的浓度。
Aim: This study was investigated to characterize the activation mechanism of a mitogen-activated protein (MAP) kinase superfamily in diabetes in aortae and cultured vascular smooth muscle cells (VSMCs) from rats.Methods: Male Sprague-Dawley rats were used for this procedure, and diabetes was induced by streptozotocin injection at 50 mg/kg. After 6 weeks, the thoracic aortae from normal and diabetic rats were removed for detection of the MAP kinase superfamily by immunoblot analysis.Results: In aortae, the protein levels of extracellular signal-regulated protein kinase (ERK)-1, c-jun NH2-terminal protein kinase (JNK)-1 and -2, and p38 increased significantly more in diabetic rats than in normal rats. In contrast, phosphorylated protein levels of ERK-1 and -2, JNK-1, and p38 were significantly more elevated in diabetic rats than in normal rats. In VSMCs from normal rats, a high concentration of glucose cultured for three days significantly increased the phosphorylated protein levels of ERKs and p38, but not JNKs, without any change of these protein levels. Serum interleukin (IL)-1 beta was significantly higher in diabetic rats than in normal rats. Several types of proinflammatory cytokine dose-dependently phosphorylated the levels of ERKs, JNK-1, and p38, but not JNK-2, in VSMCs from normal rats. In cells from diabetic rats, phosphorylated protein levels of ERKs and p38 were significantly elevated by IL-1 beta. In addition, interferon-gamma phosphorylated the levels of ERKs in diabetic cells more than in normal cells.Conclusion: Our results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature; i.e., ERKs and p38 might be mainly phosphorylated by a complex of high concentrations of glucose and of several types of proinflammatory cytokines, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1 beta, and/or additional unknown factors, except glucose.