Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells
Expression, Regulation and Function of Human Metallothioneins in Endothelial Cells
复制标题
DOI：
10.1159/000365550
复制
发表时间：
2014-01-01
影响因子：
1.7
通讯作者：
Thijssen, Victor L.
中科院分区：
文献类型：
--
作者：
Schulkens, Iris A.;Castricum, Kitty C. M.;Thijssen, Victor L.
金属硫蛋白(MTS)是一种富含半胱氨酸的小分子蛋白质，参与金属的动态平衡、金属解毒和抗氧化应激等功能。此外，一些MT已被证明可以调节促血管生成生长因子的表达，如血管内皮生长因子。关于特定MT亚型在内皮细胞(EC)中的表达和调控的详细信息有限。因此，我们在EC中对所有已知的人类MT进行了广泛的mRNA表达谱分析。我们发现基础内皮细胞的表达仅限于MT1E、MT1X、MT2A和MT3。经血清生理性激活的EC可上调MT1E和MT2a的表达，并诱导MT1M的表达。此外，暴露于锌或铜诱导了大多数MT1亚型的表达，而低氧特异性地增加了MT1E、MT1M、MT1X和MT3的表达。最后，内皮细胞中主要的MT亚型MT2a被敲除后，人脐静脉内皮细胞的增殖和发芽减少，迁移增加。总之，这些发现提供了MTS和血管生成之间的联系。(C)2014年S.Karger AG，巴塞尔
Metallothioneins (MTs) are small cysteine-rich proteins which are involved in e.g. metal homeostasis, metal detoxification and protection against oxidative stress. In addition, several MTs have been shown to regulate expression of pro-angiogenic growth factors like vascular endothelial growth factor. Detailed information about the expression and regulation of specific MT isoforms in endothelial cells (EC) is limited. We therefore performed extensive mRNA expression profiling of all known human MTs in EC. We found that the basal endothelial expression is restricted to MT1E, MT1X, MT2A, and MT3. Physiological activation of EC by exposure to serum increased the expression of MT1E and MT2A and induced the expression of MT1M. Furthermore, exposure to zinc or copper induced the expression of most MT1 isoforms, while hypoxia specifically increased the expression of MT1E, MT1M, MT1X, and MT3. Finally, knockdown of the dominant MT isoform in EC, i.e. MT2A, resulted in decreased proliferation and sprouting as well as in increased migration of human umbilical vein EC. Together, these findings provide a link between MTs and angiogenesis. (C) 2014 S. Karger AG, Basel