Golgi phosphoprotein 4 (GPP130) is a sensitive and selective cellular target of manganese exposure
Version of Record online: 8 FEB 2013
Copyright © 2012 Wiley Periodicals, Inc.
Volume 67, Issue 5, pages 205–215, May 2013
How to Cite
Masuda, M., Braun-Sommargren, M., Crooks, D. and Smith, D. R. (2013), Golgi phosphoprotein 4 (GPP130) is a sensitive and selective cellular target of manganese exposure. Synapse, 67: 205–215. doi: 10.1002/syn.21632
- Issue online: 19 MAR 2013
- Version of Record online: 8 FEB 2013
- Accepted manuscript online: 26 DEC 2012 01:12AM EST
- Manuscript Accepted: 13 DEC 2012
- Manuscript Received: 11 SEP 2012
- National Institutes of Health. Grant Numbers: R01ES018990, R01ES019222
- AF5 cells;
Chronic elevated exposure to manganese (Mn) is associated with neurocognitive and fine motor deficits in children. However, relatively little is understood about cellular responses to Mn spanning the transition between physiologic to toxic levels of exposure. Here, we investigated the specificity, sensitivity, and time course of the Golgi Phosphoprotein 4 (GPP130) response to Mn exposure in AF5 GABAergic neuronal cells, and we determined the extent to which GPP130 degradation occurs in brain cells in vivo in rats subchronically exposed to Mn. Our results show that GPP130 degradation in AF5 cells was specific to Mn, and did not occur following exposure to cobalt, copper, iron, nickel, or zinc. GPP130 degradation occurred without measurable increases in intracellular Mn levels and at Mn exposures as low as 0.54 µM. GPP130 protein was detectable by immunofluorescence in only ∼15–30% of cells in striatal and cortical rat brain slices, and Mn-exposed animals exhibited a significant reduction in both the number of GPP130-positive cells, and the overall levels of GPP130 protein, demonstrating the in vivo relevance of this Mn-specific response within the primary target organ of Mn toxicity. These results provide insight into specific mechanism(s) of cellular Mn regulation and toxicity within the brain, including the selective susceptibility of cells to Mn cytotoxicity. Synapse 67:205–215, 2013. © 2012 Wiley Periodicals, Inc.