Protection of dopaminergic cells by urate requires its accumulation in astrocytes
Article first published online: 22 AUG 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 123, Issue 1, pages 172–181, October 2012
How to Cite
Cipriani, S., Desjardins, C. A., Burdett, T. C., Xu, Y., Xu, K. and Schwarzschild, M. A. (2012), Protection of dopaminergic cells by urate requires its accumulation in astrocytes. Journal of Neurochemistry, 123: 172–181. doi: 10.1111/j.1471-4159.2012.07820.x
- Issue published online: 10 SEP 2012
- Article first published online: 22 AUG 2012
- Accepted manuscript online: 6 JUN 2012 12:07PM EST
- Received May 1, 2012; revised manuscript received June 4, 2012; accepted June 5, 2012.
- cell viability;
- MES 23.5 cells;
Urate is the end product of purine metabolism and a major antioxidant circulating in humans. Recent data link higher levels of urate with a reduced risk of developing Parkinson’s disease and with a slower rate of its progression. In this study, we investigated the role of astrocytes in urate-induced protection of dopaminergic cells in a cellular model of Parkinson’s disease. In mixed cultures of dopaminergic cells and astrocytes oxidative stress-induced cell death and protein damage were reduced by urate. By contrast, urate was not protective in pure dopaminergic cell cultures. Physical contact between dopaminergic cells and astrocytes was not required for astrocyte-dependent rescue as shown by conditioned medium experiments. Urate accumulation in dopaminergic cells and astrocytes was blocked by pharmacological inhibitors of urate transporters expressed differentially in these cells. The ability of a urate transport blocker to prevent urate accumulation into astroglial (but not dopaminergic) cells predicted its ability to prevent dopaminergic cell death. Transgenic expression of uricase reduced urate accumulation in astrocytes and attenuated the protective influence of urate on dopaminergic cells. These data indicate that urate might act within astrocytes to trigger release of molecule(s) that are protective for dopaminergic cells.