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Accumulation of labile zinc in neurons and astrocytes in the spinal cords of G93A SOD-1 transgenic mice.

Authors
Kim, TY | Hwang, JJ | Lee, JY | Shin, JH | Gwag, BJ  | Koh, JY
Citation
Neurobiology of disease, 34(2). : 221-229, 2009
Journal Title
Neurobiology of disease
ISSN
0969-99611095-953X
Abstract
Zinc dyshomeostasis may trigger oxidative stress, which is likely the key mechanism of neuronal death in amyotrophic lateral sclerosis (ALS), including familial forms such as G93A SOD-1 ALS. Since zinc binding by G93A SOD-1 is weaker than by normal SOD-1, we assessed whether labile zinc levels are altered in the spinal cords of G93A SOD-1 transgenic (Tg) mice. Whereas no zinc-containing cells were found in wild-type (WT) mice, neurons and astrocytes with high levels of labile zinc appeared in G93A SOD-1 Tg mice, in correlation with motoneuron degeneration. The level of HNE, an endogenous neurotoxic molecule, was increased around zinc-accumulating cells and mSOD-1 positive cells, suggesting a link between HNE, SOD-1 mutation and zinc accumulation. Moreover, exposure of cultured spinal neurons and astrocytes from G93A SOD-1 Tg mice to HNE increased labile zinc levels, and exposure to zinc increased 4-hydroxynonenal (HNE) levels, to a greater degree than in WT neurons and astrocytes. Administration of the zinc chelator TPEN extended survival in G93A SOD-1 Tg mice. These results indicate that zinc dyshomeostasis occurs in the spinal cords of Tg mice, and that this dyshomeostasis may contribute to motoneuron degeneration.
MeSH

DOI
10.1016/j.nbd.2009.01.004
PMID
19344646
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
곽, 병주
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