Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase.

J Neurochem 2002 Nov;83(4):984-91

Department of Molecular Pathogenesis, Division of Neurochemistry, UCL, Institute of Neurology, London, UK.

Cultured rat and human astrocytes and rat neurones were shown to release reduced glutathione (GSH). In addition, GSH oxidation was retarded by the concomitant release of a factor from the cells. One possibility is that this factor is extracellular superoxide dismutase (SOD). In support of this, the factor was found to bind heparin, have a molecular mass estimated to be between 50 and 100 kDa, and CuZn-type SOD protein and cyanide sensitive enzyme activity were demonstrated in the cell-conditioned medium. In addition, supplementation of native medium with exogenous CuZn-type SOD suppressed GSH oxidation. We propose that preservation of released GSH is essential to allow for maximal up-regulation of GSH metabolism in neurones. Furthermore, cytokine stimulation of astrocytes increased release of the extracellular SOD, and enhanced stability of GSH. This may be a protective strategy occurring in vivo under conditions of oxidative stress, and suggests that SOD mimetics may be of therapeutic use.

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http://dx.doi.org/10.1046/j.1471-4159.2002.01216.xDOI Listing
November 2002
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References

(Supplied by CrossRef)
Synthesis of the antioxidant glutathione in neurones: supply by astrocytes of cysgly as precursor for neuronal glutathione
Dringen et al.
J. Neurosci. 1999
The reaction of NO with superoxide
Huie et al.
Free Rad. Res. Commun. 1993

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