• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.293-302
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• 2002

The classical concept for iron uptake into mammalian cells has been the endocytosis of transferrin( $T_{f}$ )-bound F $e^{3+}$ via the $T_{f}$ - $T_{f}$ receptor cycle. In this case, we could not explain the uptake of F $e^{2＋}$ ion and the export of iron from endosome. Studies on iron transport revealed that other transport system exists in epithelial cells of the intestine. One of non- $T_{f}$ -receptor-mediated transport systems is Nramp2/DMT1/DCT1 which transports M $n^{＋＋}$, $Mg^{＋＋}$, Z $n^{＋＋}$, $Co^{＋＋}$, N $i^{＋＋}$ or C $u^{＋＋}$ ion as well as F $e^{+2}$ ion. DMT1 was cloned from intestines of iron-deficient rats and shown to be a hydrogen ion-coupled iron transporter and a protein regulated by absorbed dietary iron. DMT1 is founded in other cells such as cortical and hippocampal glial cells as well as endothelial cells in duodenum. Two F $e^{3+}$ ion bound to transferrin( $T_{f}$ ) are taken up via the $T_{f}$ - $T_{f}$ receptor cycle in the intestinal epithelial cell. F $e^{3+}$ in endosome was converted to F $e^{2＋}$ ion, and then exported to cytosol via DMT1. F $e^{2＋}$ ion is taken up into cytosol via DMT1. Several other transporters such as FET, FRE, CCC2, AFT1, SMF, FTR, ZER, ZIP, ZnT and CTR have been reported recently and dysfunction of the transporters are related with diseases containing Wilson's disease, Menkes disease and hemochromatosis. Evidences from several studies strongly suggest that DMT1 is the major transporter of iron in the intestine and functions critically in transport of other metal ions.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.306-312
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• 2012

Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.

• Journal of Veterinary Science
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• v.23 no.2
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• pp.26.1-26.12
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• 2022

Background: Glutamate is the main excitatory neurotransmitter. Excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal death. Parvalbumin is a calcium-binding protein that regulates calcium homeostasis. Quercetin is a polyphenol found in plant and has neuroprotective effects against neurodegenerative diseases. Objectives: We investigated whether quercetin regulates apoptosis by modulating parvalbumin expression in glutamate induced neuronal damage. Methods: Glutamate was treated in hippocampal-derived cell line, and quercetin or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment and intracellular calcium concentration and parvalbumin expression were examined. Parvalbumin small interfering RNA (siRNA) transfection was performed to detect the relation between parvalbumin and apoptosis. Results: Glutamate reduced cell viability and increased intracellular calcium concentration, while quercetin preserved calcium concentration and neuronal damage. Moreover, glutamate reduced parvalbumin expression and quercetin alleviated this reduction. Glutamate increased caspase-3 expression, and quercetin attenuated this increase in both parvalbumin siRNA transfected and non-transfected cells. The alleviative effect of quercetin was statistically significant in non-transfected cells. Moreover, glutamate decreased bcl-2 and increased bax expressions, while quercetin alleviated these changes. The alleviative effect of quercetin in bcl-2 family protein expression was more remarkable in non-transfected cells. Conclusions: These results demonstrate that parvalbumin contributes to the maintainace of intracellular calcium concentration and the prevention of apoptosis, and quercetin modulates parvalbumin expression in glutamate-exposed cells. Thus, these findings suggest that quercetin performs neuroprotective function against glutamate toxicity by regulating parvalbumin expression.

• Journal of Radiation Protection and Research
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• v.37 no.3
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• pp.123-128
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• 2012

Evidence suggests that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. This study examined whether diethyldithiocarbamate (DDC) could attenuate memory impairment, using passive avoidance and object recognition test, and suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Kiel 67 (Ki-67) and doublecortin (DCX)) in adult mice treated with gamma radiation (0.5 or 2 Gy). DDC was administered intraperitonially at a dosage of 1,000 $mg{\cdot}kg^{-1}$ of body weight at 30 min. before irradiation. In passive avoidance and object recognition memory test, the mice, trained for 1 day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells were significantly decreased. DDC treatment prior to irradiation attenuated the memory defect, and blocked the apoptotic death. DDC may attenuate memory defect in a relatively low-dose exposure of radiation in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis.

• Journal of Life Science
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• v.17 no.12
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• pp.1627-1633
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• 2007

c-Jun N-terminal kinase (JNK)-interacting protein 1 (JIP1), also known as Islet-brain 1 (IB1), is a scaffold protein that is highly expressed in neurons and pancreatic ${\beta}-cells$. In this study subcellular localization of JIP was investigated in cultured rat hippocampal neurons using an antibody that recognize all variants of JIP1, JIP-2 and JIP-3. The overall expression profile of JIP is punctate throughout soma and dendrites. Statistic analysis showed that $54.8{\pm}4.0%\;and\;94.1{\pm}4.5%$ of total JIP immunopuncta overlapped with those of excitatory postsynaptic markers SD-95 and ${\alpha}Camik$, respectively. In contrast, only $8.6{\pm}0.5%\;and\;7.3{\pm}0.5%$ of JIP clusters overlapped with those of inhibitory postsynaptic markers glycine receptor (GlyR) and gephyrin, respectively. JIP clusters overlapped or juxtaposed with SV2 but not GAD, markers for general and inhibitory nerve terminals, respectively. A substantial fraction $(29.3{\pm}1.0%)$ of flotillin immunopuncta, a marker for lipid rafts, clusters overlapped with those of JIP. In addition, JIP was highly expressed in some select ends of dendrites but minimal in axons. These data suggest important roles of JIP in excitatory postsynaptic sites, lipid rafts and dendritic ends.

• Journal of electromagnetic engineering and science
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• v.15 no.3
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• pp.123-128
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• 2015

Previously, we investigated extremely low-frequency magnetic fields (ELF-MFs) on diverse DNA damage responses, such as phosphorylated H2AX (${\gamma}H2AX$), comet tail moments, and aneuploidy production in several non-tumorigenic epithelial or fibroblast cell lines. However, the effect of ELF-MF on DNA damage responses in neuronal cells may not be well evaluated. Here, we investigated the effects of ELF-MF on the DNA damage responses in HT22 non-tumorigenic mouse neuronal cells. Exposure to a 60-Hz, 2 mT ELF-MF did not produce any increased ${\gamma}H2AX$ expression, comet tail moments, or aneuploidy formation. However, 2 mT ELF-MF transiently increased the cell number. From the results, ELF-MF could affect the DNA damage responses differently, depending on the cell lines.

• The Korean Journal of Zoology
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• v.37 no.3
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• pp.304-310
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• 1994

Using in situ hybridization, we have mapped the anatomical localization of perikarya containing myNA that codes for sonadotropin releasing hormone (GnRH) in the brains of female frogs, R. dybowskii. DNA olisomers, with sequences complementary to the GnRH portion of pro-GnRH myNA sequence, were synthesized and hybridized to paraformaldehvde-fixed, sagittal sections of the whole brain stem. The distribution of the GnRH mRNA containing cell bodies was similar to that described for GnRH peptide by immunohistochemistrv. That is, cells containing GnRH mRNA were observed in the medial septal area, anterior preoptic area, ventromedial hvpothalamus and infundibular regions. However, another cell groups which contains GnRH mRNAs were also detected by in situ hybridization in the bed nucleus of hippocampal commissure, preoptic area, nucleus infundibularis dorsalis, mesencephalic nuclei and intermediolateral cell column of spinal cord areas. These results demonstrate the feasibility of using in situ hybridization as a strategy to study the distribution of GnRH neurons and the detection of GnRH gene expression in the vertebrates.

• Korean Journal of Pharmacognosy
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• v.52 no.3
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• pp.149-156
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• 2021

Excessive glutamate can cause oxidative stress in neuronal cells and this can be the reason for neurodegenerative disease. In this study, we investigated the protective effect of Spirulina maxima hot ethanol extract on mouse hippocampal HT22 cell of which glutamate receptor has no function. HT22 cells were pre-treated with S. maxima sample at a dose dependent manner (1, 10 and 100 ㎍/ml). After an hour, glutamate was treated. Cell viability, reactive oxygen species (ROS) accumulation, Ca²⁺ influx, decrease of mitochondrial membrane potential level and glutathione related assays were followed by then. S. maxima ethanol extract improved the cell viability by suppressing the ROS and Ca²⁺ formation, retaining the mitochondrial membrane potential level and protecting the activity of the antioxidant enzymes compared with group of vehicle-treated controls. These suggest that S. maxima may decelerate the neurodegeneration by attenuating neuronal damage and oxidative stress.

• International Journal of Oral Biology
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• v.49 no.1
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• pp.10-17
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• 2024

Glutamate-mediated oxidative stress causes neuronal cell death by increasing intracellular Ca²⁺ uptake, reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) activation, and translocation of apoptosis-inducing factor (AIF) to the nucleus. In the current study, we demonstrated that corydaline exerts potent neuroprotective effects against glutamate-induced neurotoxicity. Treatment with 5 mmol/L glutamate increased cellular Ca²⁺ influx, ROS generation, MAPK activation, and AIF translocation. In contrast, corydaline treatment decreased cellular Ca²⁺ influx and ROS generation. Western blot analysis revealed that glutamate-mediated MAPK activation was attenuated by corydaline treatment. We further demonstrated that corydaline treatment inhibited the glutamate-mediated translocation of AIF to the nucleus. We propose that corydaline is a promising lead structure for the development of safe and effective neuroprotectants.

• Molecules and Cells
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• v.41 no.5
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• pp.373-380
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• 2018

Synapses and neural circuits form with exquisite specificity during brain development to allow the precise and appropriate flow of neural information. Although this property of synapses and neural circuits has been extensively investigated for more than a century, molecular mechanisms underlying this property are only recently being unveiled. Recent studies highlight several classes of cell-surface proteins as organizing hubs in building structural and functional architectures of specific synapses and neural circuits. In the present minireview, we discuss recent findings on various synapse organizers that confer the distinct properties of specific synapse types and neural circuit architectures in mammalian brains, with a particular focus on the hippocampus and cerebellum.