Vitamin D3-induced Neuroprotection is Dependent on System Xc ActivityAditi Jani1, Stephanie Crockett4, Melinda Clarke1, Brittany Coleman1 and Brian Sims1,2,3*
- *Corresponding Author:
- Brian Sims MD, PhD
Department of Pediatrics
Division of Neonatology, UAB
619 20th Street South
525 New Hillman Building, Birmingham
Alabama 35294, USA
E-Mail: [email protected]
Received date May 07, 2012; Accepted date June 12, 2012; Published date June 14, 2012
Citation: Jani A, Crockett S, Clarke M, Coleman B, Sims B (2012) Vitamin D3- induced Neuroprotection is Dependent on System Xc Activity. J Stem Cell Res Ther 2:122. doi:10.4172/2157-7633.1000122
Copyright: © 2012 Jani A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Vitamin D in the brain has been suggested as a potential neuroprotective agent. For vitamin D to have the greatest effect, its receptor must be regulated or readily available. Vitamin D3 is a pleiotropic hormone but one common neuroprotective pathway studied in our laboratory is glutathione regulation. Our objective was to investigate the intrinsic response of the vitamin D receptor under stress conditions, in in vitro preparations, and determine whether the neuroprotective effect of vitamin D is linked to the cystine-glutamate exchanger System Xc-.
Methods: In vitro, mouse cortical neural stem cells were cultured and exposed to glutamate, as a model of cellular stress, with or without vitamin D supplementation. Western Blot analysis and immunocytochemistry was used to demonstrate the protective effect of Vitamin D3.
Main results: The vitamin D receptor was upregulated under stress conditions, and vitamin D supplementation was neuroprotective for neural stem cells. Vitamin D3-induced neuroprotection was attenuated by the addition of an inhibitor of System Xc-, a protein pivotal in glutathione biosynthesis.
Conclusion: Vitamin D3 causes an increase in glutathione, suggesting that it has a major role in neuroprotection. Our results suggest that Vitamin D3-induced neuroprotection is regulated via System Xc- and glutathione biosynthesis.