• Journal of Life Science
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• v.23 no.2
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• pp.324-331
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• 2013

The addition and removal of N-acetylglucosamine (GlcNAc) molecules on serine or threonine residues of a protein is called O-GlcNAcylation. This post-translational modification occurs on both cytoplasmic and nuclear protein, and is fast and reversible as comparable to phosphorylation. In contrast to the phospho-signaling cycles, this emerging moon-lightening signaling is cycled by only two enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). The simple machinery is a good evolutionary adaptation of a cell for quick accommodation to continuously fluctuating intra- and extracellular microenvironments. Rather than "switching" on or off a specific proteins - this would be done by phosphorylation where numerous specific kinases and phosphatases are involved - O-GlcNAcylation would play a "rheostat" which would be much more delicately increase or decrease the efficacy of signal transductions in response to cellular nutrient and stress conditions. Interestingly, recent evidence indicates that O-GlcNAc is further modified by phosphorylation. The O-GlcNAc-P will upgrade the modulation efficiency of cellular processes to continuous 'analogue' level. So far, only one protein AP180 was reported to have O-GlcNAc-P on Thr310. But, proteomic data from our laboratory indicate that there are multiple O-GlcNAc-P proteins, constituting "O-GlcNAc-P'om". This will focus on the possibility of existence of "O-GlcNAc-P'om".

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.96-112
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• 2002

In the present study, we have investigated the effects of centrally administered ginsenoside Rc or Rgl on the modulation of NMDA receptor and $GABA_A$ receptor binding in rat brain. The NMDA receptor binding was analyzed by quantitative autoradiography using $[^3H]MK-801$ binding, and $GABA_A$ receptor bindings were analyzed by using $[^3H]muscimol\;and\;[^3H]flunitrazepam$ in rat brain slices. Rats were infused with ginsenoside Rc or Rg1 ($10\;{\mu}g/10{\mu}l/hr$, i.c.v.) for 7 days, through pre-implanted cannula by osmotic minipumps (Alzet, model 2ML), The levels of $[^3H]MK-801$ binding were highly decreased in part of cortex and cingulated by ginsenoside Rc and Rgl. The levels of $[^3H]muscimol$ binding were strongly elevated in almost all regions of frontal cortex by the treatment of ginseoside Rc but decreased by ginsenoside Rg 1. However, the $[^3H]flunitrazepam$ binding was not modulated by ginsenoside Rc or ginsenoside Rgl infusion. These results suggest that prolonged infusion of ginsenoside could differentially modulate $[^3H]MK-801\;and\;[^3H]muscimol$ binding in a region-specific manner. Also, we investigated the influence of centrally administered ginsenoside on the regulation of mRNA levels of the family of NMDA receptor subtypes (NR1, NR2A, NR2B, NR2C) by in situ hybridization histochemistry in the rat brain. The level of NR1 mRNA is significantly increased in temporal cortex, caudate putamen, hippocampus, and granule layer of cerebellum in Rgl-infused rats as compared to control group. The level of NR2A mRNA is elevated in the frontal cortex. In contrast, it was decreased in CAI area of hippocampus in Rgl-infused rats. However, there was no significant change of NR1 and NR2A mRNA levels in Rc-infused rats. The level of NR2B mRNA is elevated in cortex, caudate putamen, and thalamus in both Rc- and Rg-infused rats. In contrast, NR2B level is decreased in CA3 in Rgl-infused rats. The level of NR2C mRNA is increased in the granule layer of cerebellum in only Rg1 but not Rc infused rats. These results show that structure difference of ginsenoside may diversely affect the modulation of expression of NMDA receptor subunit mRNA after infusion into cerebroventricle in rats.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.583-590
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• 2021

Background: Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca²⁺]_i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods: C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results: qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion: The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.22 no.4
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• pp.430-440
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• 2021

The purpose of this study was to analyze the degree of depression, cognitive function, communication ability, and the quantitative electroencephalogram (EEG) in elderly individuals with hearing loss and to investigate their inter-relationship. Hearing-impaired elderly participants, aged 60 years or older (37 men and 26 women) who visited the S Hearing Rehabilitation Center in Y City from June 20, 2020, to September 3, 2020, participated voluntarily after a recruitment announcement.The participants' overall characteristics, depression, and cognitive functions were evaluated with a structured questionnaire. The Word Recognition Score (WRS) was evaluated with an audiometer using the Korean Standard Monosyllabic Word Lists for Adults (KS-MWL-A). The quantitative EEG was measured with dry electrodes using a 2-channel EEG on the frontal lobes Fp1 and Fp2. The results are summarized as follows: Communication ability showed a positive correlation with the left-right symmetry of the frontal lobes (**p<.01) and a negative correlation with right-brain mental distraction and stress (*p<.05). In the difference WRS test for each group, the left-right symmetry of the frontal lobes (**p<.01) showed the greatest correlation with communication ability. Our results suggest that the left-right symmetry of the frontal lobes can be a biomarker indicative of the communication ability of older people with hearing impairments.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.434-448
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• 2018

Objective: The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP. Methods: A 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts. Results: The preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression. Conclusion: The recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.398-406
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• 2018

Objective: Hospitalization of patients with delirium after visiting the emergency department (ED) is often required. However, the readmission risk after discharge from the ED should also be considered. This study aimed to explore whether (i) immediate hospitalization influences the readmission risk of patients with delirium; (ii) the readmission risk is affected by various risk factors; and (iii) the healthcare cost differs between groups within 28 days of the first ED visit. Methods: Using the National Health Insurance Research Database, the data of 2,780 subjects presenting with delirium at an ED visit from 2000 to 2008 were examined. The readmission risks of the groups of patients (i.e., patients who were and were not admitted within 24 hours of an ED visit) within 28 days were compared, and the effects of the severities of different comorbidities (using Charlson's comorbidity index, CCI), age, gender, diagnosis and differences in medical healthcare cost were analyzed. Results: Patients without immediate hospitalization had a higher risk of readmission within 3, 7, 14, or 28 days of discharge from the ED, especially subjects with more severe comorbidities ($CCI{\geq}3$) or older patients (${\geq}65years$). Subjects with more severe comorbidities or older subjects who were not admitted immediately also incurred a greater healthcare cost for re-hospitalization within the 28-day follow-up period. Conclusion: Patients with delirium with a higher CCI or of a greater age should be carefully considered for immediate hospitalization from ED for further examination in order to reduce the risk of re-hospitalization and cost of healthcare.

• Clinical Psychopharmacology and Neuroscience
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• v.16 no.4
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• pp.469-480
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• 2018

Objective: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ${\leq}7$ at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by -4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by -2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

• Journal of Korean Neurosurgical Society
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• v.62 no.5
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• pp.594-602
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• 2019

Objective : Although surgical intervention, such as percutaneous vertebroplasty (PVP), is the standard treatment for osteoporotic vertebral compression fractures (OVCFs), its effectiveness and safety are unclear. Therefore, this study compared the safety and efficacy of conservative treatment with that of PVP for acute OVCFs. Methods : Patients with single-level OVCFs who were treated conservatively with a transdermal fentanyl patch (TFP) or with PVP between March 2013 and December 2017 and followed-up for more than 1 year were retrospectively evaluated. Patients with pathologic fractures, fractures of more than two columns, or a history of PVP were excluded. Clinical outcomes (visual analog scale [VAS] scores) and radiographic factors were evaluated, including changes in the compression rate of the corresponding vertebral body at onset and after 12 months, sagittal Cobb angle at onset and after 6 and 12 months, and the incidence of adjacent compression fractures. Results : Of the 131 patients evaluated, 75 were treated conservatively using TFPs and 56 underwent PVP. We divided the patients into TFP and PVP groups. Their baseline characteristics (including sex, level of fracture, and bone mineral density T-scores) were similar, but the TFP group was significantly younger. The overall VAS score for pain showed a greater decrease during the first month (1 week after PVP) in the PVP group but remained similar in the two groups thereafter. The compression rate after 12 months increased in the TFP group but decreased in the PVP group. Five patients in the PVP group, but none in the TFP group, experienced adjacent compression fractures within 12 months. Conclusion : We compared clinical and radiological outcomes between the TFP and PVP groups. The immediate pain reduction effect was superior in the PVP group, but the final clinical outcome was similar. Although the PVP group had a better-preserved compression rate than the TFP group for 1 year, the development of adjacent fractures was significantly higher. Although TFPs seemed to be beneficial in reducing the failure rate of conservative treatment, the possibility of side effects (22.6%, 17 out of 75 patients, in this study) should be carefully monitored.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.209-217
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• 2019

Background: Ginseng is a traditional herbal medicine for human health. Ginseng contains a bioactive ligand named gintonin. The active ingredient of gintonin is lysophosphatidic acid C18:2 (LPA C18:2). We previously developed a method for gintonin-enriched fraction (GEF) preparation to mass-produce gintonin from ginseng. However, previous studies did not show the presence of other bioactive lipids besides LPAs. The aim of this study was to quantify the fatty acids, lysophospholipids (LPLs), and phospholipids (PLs) besides LPAs in GEF. Methods: We prepared GEF from white ginseng. We used gas chromatography-mass spectrometry for fatty acid analysis and liquid chromatography-tandem mass spectrometry for PL analysis, and quantified the fatty acids, LPLs, and PLs in GEF using respective standards. We examined the effect of GEF on insulin secretion in INS-1 cells. Results: GEF contains about 7.5% linoleic (C18:2), 2.8% palmitic (C16:0), and 1.5% oleic acids (C18:1). GEF contains about 0.2% LPA C18:2, 0.06% LPA C16:0, and 0.02% LPA C18:1. GEF contains 0.08% lysophosphatidylcholine, 0.03% lysophosphatidylethanolamine, and 0.13% lysophosphatidylinositols. GEF also contains about 1% phosphatidic acid (PA) 16:0-18:2, 0.5% PA 18:2-18:2, and 0.2% PA 16:0-18:1. GEFmediated insulin secretion was not blocked by LPA receptor antagonist. Conclusion: We determined four characteristics of GEF through lipid analysis and insulin secretion. First, GEF contains a large amount of linoleic acid (C18:2), PA 16:0-18:2, and LPA C18:2 compared with other lipids. Second, the main fatty acid component of LPLs and PLs is linoleic acid (C18:2). Third, GEF stimulates insulin secretion not through LPA receptors. Finally, GEF contains bioactive lipids besides LPAs.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.305-311
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• 2019

Background: Gintonin is a ginseng-derived exogenous ligand of the G protein-coupled lysophosphatidic acid (LPA) receptor. We previously reported that gintonin stimulates gliotransmitter release in primary cortical astrocytes. Astrocytes play key roles in the functions of neurovascular systems. Although vascular endothelial growth factor (VEGF) is known to influence the normal growth and maintenance of cranial blood vessels and the nervous system, there is little information about the effect of gintonin on VEGF regulation in primary astrocytes, under normal and hypoxic conditions. Methods: Using primary cortical astrocytes of mice, the effects of gintonin on the release, expression, and distribution of VEGF were examined. We further investigated whether the gintonin-mediated VEGF release protects astrocytes from hypoxia. Results: Gintonin administration stimulated the release and expression of VEGF from astrocytes in a concentration- and time-dependent manner. The gintonin-mediated increase in the release of VEGF was inhibited by the LPA1/3 receptor antagonist, Ki16425; phospholipase C inhibitor, U73122; inositol 1,4,5- triphosphate receptor antagonist, 2-APB; and intracellular $Ca^{2+}$ chelator, BAPTA. Hypoxia further stimulated astrocytic VEGF release. Gintonin treatment stimulated additional VEGF release and restored cell viability that had decreased due to hypoxia, via the VEGF receptor pathway. Altogether, the regulation of VEGF release and expression and astrocytic protection mediated by gintonin under hypoxia are achieved via the LPA receptor-VEGF signaling pathways. Conclusion: The present study shows that the gintonin-mediated regulation of VEGF in cortical astrocytes might be neuroprotective against hypoxic insults and could explain the molecular basis of the beneficial effects of ginseng on the central nervous system.