title: The Balance between Life and Death of Cells: Roles of Metallothioneins.
abstract: 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.
authors.affiliation: Section of Neuroprotection, Centre of Inflammation and Metabolism.The Panum Institute, Faculty of Health Sciences, University of Copenhagen, Denmark.
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authors.lastname: Nielsen
authors.forename: Adam
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authors.lastname: Bohr
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
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