Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During gestation, low oxygen environment is a major determinant of early placentation process, while persistent placental hypoxia leads to pregnancy-related complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). PE affects 5%-8% of all pregnancies worldwide and is a cause of maternal and fetal morbidity and mortality. During placental development, persistent hypoxia due to poor trophoblast invasion and reduced uteroplacental perfusion leads to maternal endothelial dysfunction and clinical manifestation of PE. Here we hypothesized that nuclear factor of activated T cells-5 (NFAT5), a well-known osmosensitive renal factor and recently characterized hypoxia-inducible protein, is also activated in vivo in placentas of PE and IUGR complications as well as in the in vitro model of trophoblast hypoxia. In JAR cells, low oxygen tension (1% O2) induced NFAT5 mRNA and increased its nuclear abundance, peaking at 16 h. This increase did not occur in parallel with the earlier HIF1A induction. Real-time PCR and Western blot analysis confirmed up-regulation of NFAT5 mRNA and NFAT5 nuclear content in human preeclamptic placentas and in rabbit placentas of an experimentally induced IUGR model, as compared with the control groups. In vitro lambda protein phosphatase (lambda PPase) treatment revealed that increased abundance of NFAT5 protein in nuclei of either JAR cells (16 h of hypoxia) or PE and IUGR placentas is at least partially due to NFAT5 phosphorylation. NFAT5 downstream targets aldose reductase (AR) and sodium-myo-inositol cotransporter (SMIT; official symbol SLC5A3) were not significantly up-regulated either in JAR cells exposed to hypoxia or in placentas of PE- and IUGR-complicated pregnancies, suggesting that hypoxia-dependent activation of NFAT5 serves as a separate function to its tonicity-dependent stimulation. In conclusion, we propose that NFAT5 may serve as a novel marker of placental hypoxia and ischemia independently of HIF1A.
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PMID:NFAT5 Is Up-Regulated by Hypoxia: Possible Implications in Preeclampsia and Intrauterine Growth Restriction. 2599 71

Nuclear factor of activated T cells (NFAT) is a multifunctional cytokine family. NFAT5 was recently reported to be involved in many neuronal functions, but its specific function remains unclear. In this study, our aim is to investigate whether NFAT5 overexpression can protect astrocytes against oxygen-glucose-serum deprivation/restoration (OGSD/R) damage. In vivo, rats were subjected to ischemia-reperfusion injury, resulting in increased water content, infarct volume, and expression of NFAT5 protein in rat spinal cord. After primary culture for spinal cord astrocytes, the in vitro OGSD/R model was established. The results of the CCK8 assay and flow cytometry showed that, in the OGSD/R group, astrocyte cell viability was downregulated, but astrocyte apoptosis increased. Caspase 3 activity increased as well. Levels of NFAT5, as detected by real-time quantitative PCR and western blot, decreased under OGSD/R, as did SIRT1. Commercial kits for activity assays were used to show that OGSD/R inhibited SIRT1 activation but accelerated SOD activation after OGSD/R. Next, pcDNA-NFAT5 or NFAT5 siRNA was transfected into astrocytes. Overexpression of NFAT5 not only promoted the survival of the astrocytes and SIRT1 activation under OGSD/R but also inhibited cell apoptosis and SOD activation. Moreover, overexpression of NFAT5 apparently diminished histone acetylation and promoted the nuclear transport of Nrf2. Our results show that NFAT5 protects spinal astrocytes in a manner that depends on activation of the SIRT1/Nrf2 pathway. These findings present a novel potential molecular mechanism for NFAT5 therapy in the context of spinal cord injury.
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PMID:NFAT5 protects astrocytes against oxygen-glucose-serum deprivation/restoration damage via the SIRT1/Nrf2 pathway. 2783 21