Homeostasis and cellular functions of zinc
Homeostasis and cellular functions of zinc
复制标题
DOI：
10.1002/mawe.200290008
复制
发表时间：
2002-12-01
影响因子：
1.1
通讯作者：
Beyersmann, D
中科院分区：
文献类型：
--
作者：
Beyersmann, D
锌是细胞增殖和分化所必需的元素。锌是许多蛋白质的结构成分，包括代谢酶、细胞信号蛋白和转录因子。细胞内锌的总浓度和有效离子的细胞内浓度被仔细地控制。锌的体内平衡是通过调节锌的摄取和消除来维持的，但也通过锌储存囊泡（所谓的锌小体）的细胞内隔离水平和控制核细胞质分布来维持。这些过程的主要工具是锌结合蛋白金属硫蛋白，它在细胞循环和分化过程中充当锌储存蛋白和锌转运蛋白到细胞核。越来越多的证据表明，锌在细胞信号转导的各个层面上都具有直接的信号功能。锌可调节细胞信号接收、第二信使代谢、蛋白激酶和蛋白磷酸酶活性，并可激活或抑制转录因子的DNA结合。锌离子特异性激活转录因子MTF-1，该因子控制金属硫蛋白和锌转运蛋白ZnT-1基因的表达。越来越多的证据表明锌离子是细胞增殖和分化的调节剂。如果锌的细胞外浓度超过锌体内平衡系统的能力，锌就会产生细胞毒性。细胞外锌浓度升高导致质膜锌转运系统的破坏。由此导致的细胞内锌浓度升高引起程序性细胞死亡（凋亡）的激活，而在更高的锌浓度下，细胞坏死是细胞死亡的主要形式。
Zinc is an element that is essential for cell proliferation and differentiation. Zinc is a structural constituent of a great number of proteins including metabolic enzymes, cellular signaling proteins and transcription factors. The total intracellular concentration of zinc and the intracellular concentration of the available ion are carefully controlled. The homeostasis of zinc is maintained by regulation of zinc uptake and elimination but also on the level of intracellular sequestration in zinc storing vesicles, so-called zinco-somes, and by controlled nucleo-cytoplasmic distribution. A major tool of these processes is the zinc binding protein metallothionein which serves as a zinc storing protein and a zinc transporter to the nucleus in the course of cell cycling and differentiation. There is increasing evidence for a direct signaling function of zinc at all levels of cellular signal transduction. Zinc has been found to modulate cellular signal reception, second messenger metabolism, protein kinase and protein phosphatase activities, and it may activate or inhibit the DNA binding of transcription factors. Zinc ions specifically activate the transcription factor MTF-1 which controls the expression of the genes for metallothionein and the zinc transporter protein ZnT-1. There is increasing evidence that zinc ions function as modulators of cell proliferation and differentiation. Zinc becomes cytotoxic if its extracellular concentration exceeds the capacity of the zinc homeostatic system. Elevated extracellular zinc concentrations lead to a breakdown of the zinc transporting system of the plasma membrane. The resulting enhanced intracellular zinc concentration evokes the activation of programmed cell death (apoptosis), whereas at even more elevated zinc concentration, cell necrosis is the dominant form of cell death.