Glutamate Increases In Vitro Survival and Proliferation and Attenuates Oxidative Stress-Induced Cell Death in Adult Spinal Cord-Derived Neural Stem/Progenitor Cells via Non-NMDA Ionotropic Glutamate Receptors

2016 ◽  
Vol 25 (16) ◽  
pp. 1223-1233 ◽  
Author(s):  
Laureen D. Hachem ◽  
Andrea J. Mothe ◽  
Charles H. Tator
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Cell Death ◽  
Glutamate Receptors ◽  
Progenitor Cells ◽  
Ionotropic Glutamate Receptors ◽  
Neural Stem Progenitor Cells ◽  
Adult Spinal Cord ◽  
In Vitro Survival

scholarly journals Characterization of Human Hippocampal Neural Stem/Progenitor Cells and Their Application to Physiologically Relevant Assays for Multiple Ionotropic Glutamate Receptors

2014 ◽  
Vol 19 (8) ◽  
pp. 1174-1184 ◽  
Author(s):  
Kazuyuki Fukushima ◽  
Yoshikuni Tabata ◽  
Yoichi Imaizumi ◽  
Naohiro Kohmura ◽  
Michiko Sugawara ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
Progenitor Cells ◽  
Brain Region ◽  
Long Term Potentiation ◽  
Ionotropic Glutamate Receptors ◽  
Neural Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Neural Stem Progenitor Cells

The hippocampus is an important brain region that is involved in neurological disorders such as Alzheimer disease, schizophrenia, and epilepsy. Ionotropic glutamate receptors—namely, N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs), and kainic acid (KA) receptors (KARs)—are well known to be involved in these diseases by mediating long-term potentiation, excitotoxicity, or both. To predict the therapeutic efficacy and neuronal toxicity of drug candidates acting on these receptors, physiologically relevant systems for assaying brain region–specific human neural cells are necessary. Here, we characterized the functional differentiation of human fetal hippocampus–derived neural stem/progenitor cells—namely, HIP-009 cells. Calcium rise assay demonstrated that, after a 4-week differentiation, the cells responded to NMDA (EC50 = 7.5 ± 0.4 µM; n = 4), AMPA (EC50 = 2.5 ± 0.1 µM; n = 3), or KA (EC50 = 33.5 ± 1.1 µM; n = 3) in a concentration-dependent manner. An AMPA-evoked calcium rise was observed in the absence of the desensitization inhibitor cyclothiazide. In addition, the calcium rise induced by these agonists was inhibited by antagonists for each receptor—namely, MK-801 for NMDA stimulation (IC50 = 0.6 ± 0.1 µM; n = 4) and NBQX for AMPA and KA stimulation (IC50 = 0.7 ± 0.1 and 0.7 ± 0.03 µM, respectively; n = 3). The gene expression profile of differentiated HIP-009 cells was distinct from that of undifferentiated cells and closely resembled that of the human adult hippocampus. Our results show that HIP-009 cells are a unique tool for obtaining human hippocampal neural cells and are applicable to systems for assay of ionotropic glutamate receptors as a physiologically relevant in vitro model.

Abstract 217: Long Non-coding RNA Myocardial Infarction-associated Transcript (MIAT) Protects Cardiac Progenitor Cells From Oxidative Stress-induced Cell Death

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Liu Yang ◽  
Yang Yu ◽  
Baron Arnone ◽  
Chan Boriboun ◽  
Jiawei Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cell Death ◽  
Progenitor Cells ◽  
Cardiac Cells ◽  
Border Zone ◽  
Mouse Heart ◽  
Cardiac Progenitor Cells

Background: Long non-coding RNAs (lncRNAs) are an emerging class of RNAs with no or limited protein-coding capacity; a few of which have recently been shown to regulate critical biological processes. Myocardial infarction-associated transcript (MIAT) is a conserved mammalian lncRNA, and single nucleotide polymorphisms (SNPs) in 6 loci of this gene have been identified to be strongly associated with the incidence and severity of human myocardial infarction (MI). However, whether and how MIAT impacts on the pathogenesis of MI is unknown. Methods & Results: Quantitative RT-PCR analyses revealed that MIAT is expressed in neonatal mouse heart and to a lesser extent in adult heart. After surgical induction of MI in adult mice, MIAT starts to increase in 2 hours, peaks at 6 hours in atria and 12 hours in ventricles, and decreases to baseline at 24 hours. Fluorescent in situ hybridization (FISH) revealed a slight increase in the number of MIAT-expressing cells in the infarct border zone at 12 hours post-MI. Moreover, qRT-PCR analyses of isolated cardiac cells revealed that MIAT is predominantly expressed in cardiosphere-derived cardiac progenitor cells (CPCs). Treatment of CPCs with H 2 O 2 led to a marked upregulation of MIAT, while knockdown (KD) of MIAT resulted in a significantly impaired cell survival in vitro with H 2 O 2 treatment and in vivo after administered in the ischemic/reperfused heart. Notably, bioinformatics prediction and RNA immunoprecipitation identified FUS (fused in sarcoma) as a novel MIAT-interacting protein. FUS-KD CPCs displayed reduced cell viability and increased apoptosis under oxidative stress. Furthermore, MIAT overexpression enhanced survival of WT CPCs but not FUS-KD CPCs, suggesting that the protective role of MIAT is mediated by FUS. Conclusions: MIAT interacts with FUS to protect CPCs from oxidative stress-induced cell death.

scholarly journals Long-distance effects of inflammation on differentiation of adult spinal cord neural stem/progenitor cells

2015 ◽  
Vol 288 ◽  
pp. 47-55 ◽  
Author(s):  
Lisa Arvidsson ◽  
Ruxandra Covacu ◽  
Cynthia Perez Estrada ◽  
Sreenivasa Raghavan Sankavaram ◽  
Mikael Svensson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Progenitor Cells ◽  
Long Distance ◽  
Distance Effects ◽  
Neural Stem Progenitor Cells ◽  
Adult Spinal Cord
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