Nielsen Allan Evald, Bohr Adam, Penkowa Milena
Section of Neuroprotection, Centre of Inflammation and Metabolism.The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Denmark.
Biomark Insights. 2007 Feb 7;1:99-111.
Metallothionein (MT) is a highly conserved, low-molecular-weight, cysteine-rich protein that occurs in 4 isoforms (MT-I to MT-IV), of which MT-I+II are the major and best characterized proteins.This review will focus on mammalian MT-I+II and their functional impact upon cellular survival and death, as seen in two rather contrasting pathological conditions: Neurodegeneration and neoplasms. MT-I+II have analogous functions including: 1) Antioxidant scavenging of reactive oxygen species (ROS); 2) Cytoprotection against degeneration and apoptosis; 3) Stimulation of cell growth and repair including angiogenesis/revascularization, activation of stem/progenitor cells, and neuroregeneration. Thereby, MT-I+II mediate neuroprotection, CNS restoration and clinical recovery during neurodegenerative disorders. Due to the promotion of cell survival, increased MT-I+II levels have been associated with poor tumor prognosis, although the data are less clear and direct causative roles of MT-I+II in oncogenesis remain to be identified.The MT-I+II molecular mechanisms of actions are not fully elucidated. However, their role in metal ion homeostasis might be fundamental in controlling Zn-dependent transcription factors, protein synthesis, cellular energy levels/metabolism and cell redox state.Here, the neuroprotective and regenerative functions of MT-I+II are reviewed, and the presumed link to oncogenesis is critically perused.
金属硫蛋白（MT）是一种高度保守、低分子量、富含半胱氨酸的蛋白质，有4种异构体（MT-I至MT-IV），其中MT-I+II是主要且特征最明确的蛋白质。本综述将聚焦于哺乳动物的MT-I+II及其在细胞存活和死亡方面的功能影响，这在两种截然不同的病理状况中可见：神经退行性变和肿瘤。MT-I+II具有类似的功能，包括：1）清除活性氧（ROS）的抗氧化作用；2）针对变性和凋亡的细胞保护作用；3）刺激细胞生长和修复，包括血管生成/血管再形成、干细胞/祖细胞的激活以及神经再生。因此，MT-I+II在神经退行性疾病中介导神经保护、中枢神经系统恢复和临床康复。由于促进细胞存活，MT-I+II水平升高与肿瘤预后不良相关，尽管数据尚不明确，MT-I+II在肿瘤发生中的直接因果作用仍有待确定。MT-I+II的分子作用机制尚未完全阐明。然而，它们在金属离子稳态中的作用可能在控制锌依赖性转录因子、蛋白质合成、细胞能量水平/代谢和细胞氧化还原状态方面至关重要。在此，对MT-I+II的神经保护和再生功能进行综述，并对其与肿瘤发生的假定联系进行批判性审视。
