Melatonin Induces Neuroprotection via System Xc Regulation in Neural Stem CellsMelinda Clarke1, Stephanie Crockett1 and Brian Sims1,2,3*
- *Corresponding Author:
- Brian Sims MD, PhD
Departments of Pediatrics
Division of Neonatology, UAB
619 20th Street South, 525 New Hillman Building
Birmingham, Alabama 35294, USA
E-mail: [email protected]
Received date: April 04, 2012; Accepted date: May 02, 2012; Published date: May 04, 2012
Citation: Clarke M, Crockett S, Sims B (2012) Melatonin Induces Neuroprotection via System Xc Regulation in Neural Stem Cells. J Stem Cell Res Ther 2:120. doi:10.4172/2157-7633.1000120
Copyright: © 2012 Clarke M, 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.
Hypoxic-brain injury is a major cause of neonatal morbidity and mortality. However, melatonin (N-acetyl-5- methoxytryptamine) has been identified as an indirect anti-oxidant and direct free radical scavenger that could possibly reduce the injurious effects of hypoxic-ischemic brain injury in neonatal infants. Hypoxia-ischemia leads to multiple consequences such as an increase in extracellular glutamate. Yet the many mechanisms involved in melatonin-induced neuroprotection are still under investigation. We have hypothesized that melatonin could induce neuroprotection by increasing levels of cystine glutamate exchanger (xCT), an amino acid transporter as shown in previous work in our laboratory. Mouse neural stem cells were used for all in vitro studies for western blot analysis. In dose-response studies, melatonin increases xCT expression by 2.43 ± 0.81, 3.58 ± 0.6, 3.21 ± 1.13, 3.30 ± 0.96 and 3.48 ± 0.30 (p < 0.01) folds at 1 nM, 10 nM, 100 nM, 1 µM and 10 µM concentrations respectively in neural stem cells. In time-course studies, melatonin increases xCT by 2.60 ± 0.97, 2.65 ± 0.27, 3.29 ± 0.40, and 3.57 ± 0.60 fold at 4 hours, 8 hours, 12 hours, and 24 hours. Melatonin increases cystine uptake. System Xc inhibition decreased cell viability. These results suggest that melatonin may induce neuroprotection by increasing xCT expression and activity.