Zinc amplifies mSOD1-mediated toxicity in a transgenic mouse model of amyotrophi

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Neurosci Lett. 2003 Dec 11;352(3):175-8.

Zinc amplifies mSOD1-mediated toxicity in a transgenic mouse model of

amyotrophic lateral sclerosis.

Groeneveld GJ, de Leeuw van Weenen J, van Muiswinkel FL, Veldman H, Veldink

JH, Wokke JH, Bar PR, van den Berg LH.

Rudolf Magnus Institute of Neuroscience, Department of Neurology and

Neurosurgery, G.03.228, University Medical Center Utrecht, P.O. Box 85500,

3508 GA, Utrecht, The Netherlands.

Transgenic mice overexpressing the human mutated form (G93A) of

Cu,Zn-superoxide dismutase (mSOD1) develop motor neuron degeneration

resembling amyotrophic lateral sclerosis.

In vitro studies have shown that mSOD1-induced, reactive oxygen

species-mediated apoptosis of motor neurons depends on the presence of

copper and the relative absence of zinc.

Oral intake of zinc sulphate induces the expression of metallothioneins,

enzymes that decrease oxidative stress, and leads to higher serum zinc, and

lower copper levels.

We therefore tested the effect of chronic oral administration of zinc

sulfate (0.075 and 0.375 g/kg) on disease onset and survival of mSOD1

transgenic mice.

We observed that zinc sulfate, rather than prolonging survival, decreased

survival.

We conclude that zinc sulfate amplifies the mSOD1 transgenic mouse

phenotype.

This finding may shed more light on the role of zinc in mSOD1-mediated

toxicity.

PMID: 14625013 [PubMed - in process]

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