Li Jie, Liu Ying, Ru Binggen
National Key Laboratory of Protein Engineering, College of Life Sciences, Peking University, Beijing 100871, China.
Cell Biol Int. 2005 Oct;29(10):843-8. doi: 10.1016/j.cellbi.2005.05.008.
Metallothioneins (MTs) are thought to participate in a wide variety of physiological roles, but the mechanisms involved are still unclear. The study was designed to examine the possible factors related to these mechanisms. Methods, including transfection, MTT assay and flow cytometry, were used to investigate the effect of MTs on cell viability and their interactions with cadmium and zinc in HEK293 cells. The results showed that transient overexpression of human MT1A, MT2 and MT3 genes dynamically affected cell viability, and the effect was influenced by zinc and cadmium ions. Overexpressed MTs with added zinc showed a greater inhibitory effect on cell viability. Overexpressed MTs protected cells against low concentrations of cadmium ions (10 microM), but increased cell death in response to high concentrations (20-50 microM). Out of the three MTs, MT1A was more efficient than MT2 and MT3 in its resistance to cadmium (10 microM), and MT3 together with zinc showed more cell growth inhibition than MT1 and MT2. These results indicate that both of the divalent metal ions that could bind MTs, as well as the individual MT isoforms, affect the role of MTs on cell viability, which may explain in part why the comprehensive effect of MTs on the cells was elusive.
金属硫蛋白（MTs）被认为参与多种生理功能，但其涉及的机制仍不清楚。本研究旨在探究与这些机制相关的可能因素。采用转染、MTT 法和流式细胞术等方法，研究 MTs 对 HEK293 细胞活力的影响及其与镉和锌的相互作用。结果表明，人 MT1A、MT2 和 MT3 基因的瞬时过表达动态影响细胞活力，且该效应受锌和镉离子影响。添加锌的过表达 MTs 对细胞活力的抑制作用更大。过表达的 MTs 可保护细胞免受低浓度镉离子（10 microM）的影响，但在高浓度（20 - 50 microM）时会增加细胞死亡。在这三种 MTs 中，MT1A 在抵抗镉（10 microM）方面比 MT2 和 MT3 更有效，并且 MT3 与锌共同作用时比 MT1 和 MT2 表现出更强的细胞生长抑制作用。这些结果表明，能够结合 MTs 的二价金属离子以及单个 MT 异构体均会影响 MTs 对细胞活力的作用，这可能部分解释了为何 MTs 对细胞的综合作用难以捉摸。
