Abstract
Although c-Fos expression in mitochondria is known to increase under excitatory injury via kainic acid or N-methyl-d-aspartate injection, the authentic function of c-Fos in mitochondria remains unknown. We found that c-Fos expression in the mitochondria of neuroblastoma Neuro2a cells was augmented by oxygen and glucose deprivation (OGD), which is a common in vitro model for brain ischemia. Then we demonstrated that Neuro2a cells stably expressing c-Fos exclusively in the mitochondria were more vulnerable to stressors such as OGD, rotenone (which is known to induce mitochondrial dysfunction) and hydrogen peroxide (a reactive oxygen species). Since mitochondrial dysfunction and the generation of reactive oxygen species are known to be caused by OGD, our findings indicate that mitochondrial c-Fos increases neuronal vulnerability to brain ischemia. This suggests that mitochondrial c-Fos play a potential role in inducing neuronal death on, and can therefore act as a potential drug target for brain ischemia.
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Acknowledgments
This work was supported by a Grant-in-Aid for Young Scientists (B) (22790256) from The Ministry of Education, Culture, Sports, Science and Technology (MEXT). We thank Drs. Takashi Kurihara and Kazuhiko Inoue for their helpful discussion and advice. We thank Ms. Izumi Fujisima for her technical contribution. We wish to thank the Joint Research Laboratory, Kagoshima University Graduate School of Medical and Dental Sciences, for the use of its facilities and equipment.
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Kambe, Y., Miyata, A. Mitochondrial c-Fos May Increase the Vulnerability of Neuro2a Cells to Cellular Stressors. J Mol Neurosci 59, 106–112 (2016). https://doi.org/10.1007/s12031-015-0710-7
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DOI: https://doi.org/10.1007/s12031-015-0710-7