Selenium: potent stimulator of tyrosyl phosphorylation and activator of MAP kinase.
Selenium: potent stimulator of tyrosyl phosphorylation and activator of MAP kinase.
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DOI：
10.1016/s0167-4889(96)00140-1
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发表时间：
1997-03
期刊：
影响因子：
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通讯作者：
S. Stapleton;Ginny L. Garlock;Lisa A. Foellmi-Adams;R. Kletzien
中科院分区：
文献类型：
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作者：
S. Stapleton;Ginny L. Garlock;Lisa A. Foellmi-Adams;R. Kletzien
硒是一种必需的生物微量元素，是多种酶的重要组成部分，在低浓度时可作为抗氧化剂，在高浓度时可用作抗癌剂，因此近年来作为营养补充剂得到了广泛的应用。据报道，硒在血糖水平的正常化和某些胰岛素介导的代谢过程的调节方面也起到了类似胰岛素的作用。然而，关于这种类似胰岛素的作用发生的途径(S)，工作做得很少。在这项研究中，我们研究了硒在两种不同类型的胰岛素反应细胞，原代大鼠肝细胞和3T3 L1脂肪细胞中表现出类似胰岛素的特性的机制。我们发现，与胰岛素信号级联相关的两种蛋白质，胰岛素受体的β亚单位和胰岛素受体-1，在硒存在的情况下，酪氨酸磷酸化增加。Se激活的第三种信号蛋白，MAP激酶，不仅与胰岛素信号转导有关，而且还与生长因子介导的其他反应有关。用凝胶内MAP激酶活性测定，我们证明了当肝细胞或脂肪细胞在硒的存在下孵育时，P42和P44 MAP激酶都被激活。除了激活这些特定的蛋白质外，我们还发现硒最终也深刻地影响了整个酪氨酸磷酸化。因此，我们的结果表明，硒不仅增加了胰岛素信号级联中识别的蛋白质的磷酸化，而且还影响了细胞的整体磷酸化状态。
Selenium, an essential biological trace element, is an integral component of several enzymes, and its use as a nutritional supplement has been popularized recently due to its potential role in low concentrations as an antioxidant and in higher concentrations as an anticancer agent. Selenium has also been reported to act as an insulin-mimetic agent with regard to normalization of blood glucose levels and regulation of some insulin-mediated metabolic processes. Little work, however, has been done concerning the pathway(s) by which this insulin-mimetic action occurs. In this study, we investigated the mechanism by which selenate exhibits insulin-mimetic properties in two different insulin responsive cell types, primary rat hepatocytes and 3T3 L1 adipocytes. We found that two proteins associated with the insulin signal cascade, the β-subunit of the insulin receptor and IRS-1, increased in tyrosyl phosphorylation in the presence of selenium. The third identified selenium activated signal protein, MAP kinase, has been implicated not only in the insulin signal transduction pathway but also in other growth factor-mediated responses. Using an in-gel activity assay for MAP kinase, we demonstrated that both the p42 and p44 MAP kinases are activated when either hepatocytes or adipocytes are incubated in the presence of selenate. In addition to the activation of these specific proteins, we found that selenium also eventually profoundly affected overall tyrosyl phosphorylation. Our results therefore show that selenium not only increased the phosphorylation of proteins identified in the insulin signal cascade but also affected the overall phosphorylation state of the cell.