title: Mitochondrial c-Fos May Increase the Vulnerability of Neuro2a Cells to Cellular Stressors.
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.
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagosima-shi, Kagoshima, 890-8544, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kambe
authors.affiliation: Department of Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagosima-shi, Kagoshima, 890-8544, Japan. amiyata@m3.kufm.kagoshima-u.ac.jp.
authors.forename: Atsuro
authors.initials: A
authors.lastname: Miyata
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012402:Rotenone / Q000633:toxicity
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D012402:Rotenone; D005947:Glucose
keywords: Mitochondria; Neuronal death; c-Fos