Nuclear factor of activated T cells 5 deficiency increases the severity of neuronal cell death in ischemic injury

Abstract

Nuclear factor of activated T cells 5 (NFAT5) has been implicated in regulating several genes that are thought to be neuroprotective in ischemic injury. Because of the embryonic lethality of NFAT5 knockout (NFAT5) mice, the heterozygous (NFAT5) mice were used to study the in vivo role of NFAT5 in hypoxia/ischemia (H/I) condition. The NFAT5 mice exhibited more severe neurological deficits, larger infarct area and edema formation associated with increased aquaporin 4 expressions in the brain. Under in vitro H/I condition, increased apoptotic cell death was found in NFAT5-/- neurons. Moreover, SMIT, a downstream to NFAT5, was upregulated in NFAT5 neurons, while the SMIT level could not be upregulated in NFAT5-/- neurons under H/I condition. The elevation of reactive oxygen species generation in NFAT5 -/- neurons under H/I condition further confirmed that NFAT5 -/- neurons were more susceptible to oxidative stress. The present study demonstrated that activation of NFAT5 and its downstream SMIT induction is important in protecting neurons from ischemia-induced oxidative stress. Copyright © 2012 S. Karger AG, Basel.