Nuclear Factor of Activated T Cells 5 Deficiency Increases the Severity of Neuronal Cell Death in Ischemic Injury

[摘要] 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.

[学科分类] 神经科学

[关键词] Knockout;NFAT5;Ischemia;SMIT;Oxidative stress