title: 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.
authors.affiliation: Department of Anatomy, Li Ka Shing Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, SAR, China.
authors.forename: Keri Man Chi
authors.initials: KM
authors.lastname: Mak
authors.forename: Amy Cheuk Yin
authors.initials: AC
authors.lastname: Lo
authors.forename: Amy Ka Man
authors.initials: AK
authors.lastname: Lam
authors.forename: Patrick Ka Kit
authors.initials: PK
authors.lastname: Yeung
authors.forename: Ben Chi Bun
authors.initials: BC
authors.lastname: Ko
authors.forename: Stephen Sum Man
authors.initials: SS
authors.lastname: Chung
authors.forename: Sookja Kim
authors.initials: SK
authors.lastname: Chung
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D015153:Blotting, Western; D002545:Brain Ischemia / Q000235:genetics* / Q000473:pathology*; D016923:Cell Death / Q000235:genetics* / Q000502:physiology*; D002478:Cells, Cultured; D006982:Hypertonic Solutions; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology*; D009997:Osmotic Pressure; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D027981:Symporters / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D006982:Hypertonic Solutions; C492200:Nfat5 protein, mouse; D017382:Reactive Oxygen Species; C508355:SLC5A3 protein, mouse; D027981:Symporters; D014157:Transcription Factors; D007770:L-Lactate Dehydrogenase; D008156:Luciferases