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5TH INTERNATIONAL CONFERENCE ON METALLOTHIONEIN SYMPOSIUM PAPERS

Metallothioneins: Mercury Species-Specific Induction and Their Potential Role in Attenuating Neurotoxicity

Michael Aschner^*,1, Tore Syversen, Diogo O. Souza and Joao B.T. Rocha

^* Departments of Pediatrics, Pharmacology, and the Kennedy Center, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Clinical Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway; Departamento de Química, Centro de Ciências da Naturais e Exatas, Universidade Federal de Santa Maria; and Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

To whom requests for reprints should be addressed at ¹ Department of Pediatrics, B-3307 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232-2495. E-mail: michael.aschner{at}vanderbilt.edu

Abstract

Metallothionein (MT) proteins are widespread in bacteria, fungi, plants, and eukaryotic species. They are of low molecular weight (6–7 kDa) and of the 60+ amino acid residues, 20 are cysteines. Functions attributed to MTs include the sequestration and dispersal of metal ions, primarily in zinc and copper homeostasis; regulation of the biosynthesis and activity of zinc metalloproteins, most notably zinc-dependent transcription factors; and cellular cytoprotection from reactive oxygen species, ionizing radiation, electrophilic anticancer drugs and mutagens, and metals. Observations on the abundance of MTs within the central nervous system (CNS) and the identification of a brain-specific isoform, MT-III, suggest that it might have important neurophysiological and neuromodulatory functions. Reinforced by the potential involvement of MT-III in a number of neurodegenerative disorders, the role of MTs in the CNS has become an intense focus of scientific pursuit. This manuscript represents a survey on the ability of MTs to modulate mercury neurotoxicity, a neurotoxin that has been implied to play an etiologic role in Minamata disease, erethism, and autism, just to name a few.

Key Words: metallothionein • mercury • neurotoxicity