The role of metallothionein II in neuronal differentiation and survival.
Metallothionein I and II (MT-I+II) are antioxidant and tissue protective factors. We have previously shown that MT-I+II prevent oxidative stress and apoptotic cell death and are of therapeutic value in brain inflammation. However, MT-I+II are expressed in glia and it remains to be elucidated if MT-I+II can affect neurons directly. It is likely that MT isoforms could be beneficial also during neurodegenerative disorders. In this study, we have examined if MT-II affects survival and neurite extension of dopaminergic and hippocampal neurons. We show for the first time that MT-II treatment can significantly stimulate neurite extension from both dopaminergic and hippocampal neurons. Moreover, MT-II treatment significantly increases survival of dopaminergic neurons exposed to 6-hydroxydopamine (6-OHDA) and protects significantly hippocampal neurons from amyloid beta-peptide-induced neurotoxicity. Accordingly, treatment with MT-II may be of therapeutic value in neurodegenerative disorders.
Køhler
Lene B
LB
Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Berezin
Vladimir
V
Bock
Elisabeth
E
Penkowa
Milena
M
D018663:Adrenergic Agents / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008668:Metallothionein / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D018663:Adrenergic Agents; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D016627:Oxidopamine; D008668:Metallothionein; D004298:Dopamine