Zingg Jean-Marc
Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28, 3012 Bern, Switzerland.
Mol Aspects Med. 2007 Oct-Dec;28(5-6):481-506. doi: 10.1016/j.mam.2006.12.009. Epub 2007 Jan 12.
The ability of vitamin E to modulate signal transduction and gene expression has been observed in numerous studies; however, the detailed molecular mechanisms involved are often not clear. The eight natural vitamin E analogues and synthetic derivatives affect signal transduction with different potency, possibly reflecting their different ability to interact with specific proteins. Vitamin E modulates the activity of several enzymes involved in signal transduction, such as protein kinase C, protein kinase B, protein tyrosine kinases, 5-, 12-, and 15-lipoxygenases, cyclooxygenase-2, phospholipase A2, protein phosphatase 2A, protein tyrosine phosphatase, and diacylglycerol kinase. Activation of some these enzymes after stimulation of cell surface receptors with growth factors or cytokines can be normalized by vitamin E. At the molecular level, the translocation of several of these enzymes to the plasma membrane is affected by vitamin E, suggesting that the modulation of protein-membrane interactions may be a common theme for vitamin E action. In this review the main effects of vitamin E on enzymes involved in signal transduction are summarized and the possible mechanisms leading to enzyme modulation evaluated. The elucidation of the molecular and cellular events affected by vitamin E could reveal novel strategies and molecular targets for developing similarly acting compounds.
在众多研究中已观察到维生素E调节信号转导和基因表达的能力；然而，其中涉及的详细分子机制往往并不清楚。八种天然维生素E类似物和合成衍生物以不同的效力影响信号转导，这可能反映了它们与特定蛋白质相互作用的不同能力。维生素E调节几种参与信号转导的酶的活性，如蛋白激酶C、蛋白激酶B、蛋白酪氨酸激酶、5-、12-和15-脂氧合酶、环氧化酶-2、磷脂酶A2、蛋白磷酸酶2A、蛋白酪氨酸磷酸酶和二酰基甘油激酶。在用生长因子或细胞因子刺激细胞表面受体后，这些酶中的一些酶的激活可被维生素E正常化。在分子水平上，维生素E会影响其中几种酶向质膜的转位，这表明调节蛋白质-膜相互作用可能是维生素E作用的一个共同主题。在这篇综述中，总结了维生素E对参与信号转导的酶的主要影响，并评估了导致酶调节的可能机制。对受维生素E影响的分子和细胞事件的阐明可能会揭示开发具有类似作用的化合物的新策略和分子靶点。
