29 results on '"Seikwan Oh"'
Search Results
2. Alleviation of Atopic Dermatitis Lesions by a Benzylideneacetophenone Derivative via the MAPK Signaling Pathway
- Author
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Mijin Kim, Seungmin Kang, Bongjun Sur, and Seikwan Oh
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0301 basic medicine ,medicine.medical_specialty ,MAP Kinase Signaling System ,medicine.medical_treatment ,Immunology ,Immunoglobulin E ,Dermatitis, Atopic ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Trimellitic anhydride ,Chalcone ,0302 clinical medicine ,Internal medicine ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Mast Cells ,Lymph node ,Cells, Cultured ,Interleukin 4 ,Propiophenones ,biology ,business.industry ,Atopic dermatitis ,medicine.disease ,030104 developmental biology ,Endocrinology ,Cytokine ,medicine.anatomical_structure ,chemistry ,Phthalic Anhydrides ,030220 oncology & carcinogenesis ,biology.protein ,Phorbol ,Antibody ,business - Abstract
This experiment was conducted to investigate the effects of a benzylideneacetophenone derivative ((2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one (JC3)) on trimellitic anhydride (TMA)-induced atopic dermatitis (AD)-like symptoms in mice. To induce AD, the dorsal skins of mice were treated with 5% TMA on day 0 and both ears were treated with 5% TMA on day 5 and with 2% TMA from day 6 to day 14. JC3 (1, 5, 10 mg/kg, i.p.) was treated once daily from day 9 to day 14 before TMA treatment. Histological analysis was performed and auricular lymph node weights, ear thicknesses, skin water contents, scratching behaviors, and serum immunoglobulin (IgE) and IFN-γ, and interleukin-4 (IL-4) levels in serum and ear tissues were determined. In addition, the anti-AD activity of JC3 was investigated on phorbol 12-myristate 13-acetate (PMA)-stimulated human mast cells (HMC-1 cells) derived from patients. Levels of TNF-α, IL-4, and mitogen-activated protein kinase (MAPK) were investigated after treating cultured cells with JC3. Treating mice with JC3 (10 mg/kg) significantly decreased ear thicknesses, lymph node weights, skin scores, skin water contents, scratching behavior, and IFN-γ, IL-4 cytokine levels, and serum IgE levels. Moreover, treatment with JC3 (10 mg/kg) significantly decreased serum and ear tissues levels of IFN-γ and IL-4 in AD mice. Furthermore, treatment with JC3 at 10 μg/ml reduced TNF-α and IL-4 levels and decreased MAPK phosphorylation in the HMC-1 cells. The results of this study provide a molecular basis for developing new therapeutics for the treatment of various inflammatory diseases, such as, eczema, asthma, and AD.
- Published
- 2019
3. Morphine Dependence is Attenuated by Treatment of 3,4,5-Trimethoxy Cinnamic Acid in Mice and Rats
- Author
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Taddesse Yayeh, Seungmin Kang, Heeyeon Shin, Bongjun Sur, Seikwan Oh, and Sohyeon Moon
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Male ,0301 basic medicine ,medicine.medical_specialty ,Striatum ,Nucleus accumbens ,Biochemistry ,Rats, Sprague-Dawley ,Mice ,Random Allocation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Internal medicine ,Conditioning, Psychological ,medicine ,Animals ,Cells, Cultured ,Cerebral Cortex ,Dose-Response Relationship, Drug ,Chemistry ,General Medicine ,Conditioned place preference ,Rats ,Mice, Inbred C57BL ,Blot ,Treatment Outcome ,030104 developmental biology ,Endocrinology ,Cinnamates ,Morphine ,NMDA receptor ,Licking ,Morphine Dependence ,030217 neurology & neurosurgery ,medicine.drug ,FOSB - Abstract
The effect of 3, 4, 5-trimethoxy cinnamic acid (TMCA) against morphine-induced dependence in mice and rats was investigated. Mice were pretreated with TMCA and then morphine was injected intraperitoneally; whereas rats were treated with TMCA (i.p.) and infused with morphine into the lateral ventricle of brain. Naloxone-induced morphine withdrawal syndrome and conditioned place preference test were performed. Moreover, western blotting and immunohistochemistry were used to measure protein expressions. Number of naloxone-precipitated jumps and conditioned place preference score in mice were attenuated by TMCA. Likewise, TMCA attenuated morphine dependent behavioral patterns such as diarrhea, grooming, penis licking, rearing, teeth chattering, and vocalization in rats. Moreover, the expression levels of pNR1and pERK in the frontal cortex of mice and cultured cortical neurons were diminished by TMCA. In the striatum, pERK expression was attenuated despite unaltered expression of pNR1 and NR1. Interestingly, morphine-induced elevations of FosB/ΔFosB+ cells were suppressed by TMCA (50, 100 mg/kg) in the nucleus accumbens sub-shell region of mice. In conclusion, TMCA could be considered as potential therapeutic agent against morphine-induced dependence.
- Published
- 2019
4. Inhibition of Carrageenan/Kaolin-Induced Arthritis in Rats and of Inflammatory Cytokine Expressions in Human IL-1β-Stimulated Fibroblast-like Synoviocytes by a Benzylideneacetophenone Derivative
- Author
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Seungmin Kang, Seikwan Oh, Mijin Kim, and Bongjun Sur
- Subjects
0301 basic medicine ,medicine.drug_class ,medicine.medical_treatment ,Interleukin-1beta ,Immunology ,Anti-Inflammatory Agents ,Arthritis ,Pharmacology ,Carrageenan ,Benzylidene Compounds ,Anti-inflammatory ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Humans ,Immunology and Allergy ,Fibroblast-like synoviocytes ,Prostaglandin E2 ,Kaolin ,Inflammation ,Analgesics ,Propiophenones ,Chemistry ,Benzylideneacetophenone derivative ,Interleukin ,medicine.disease ,Arthritis, Experimental ,Synoviocytes ,Rats ,030104 developmental biology ,Cytokine ,030220 oncology & carcinogenesis ,Cytokines ,Original Article ,Tumor necrosis factor alpha ,medicine.drug - Abstract
The benzylideneacetophenone derivative JC3 [(2E)-3-(4-hydroxy-3-methoxyphenyl)phenylpro-2-en-l-one] (JC3) was synthesized by modifying yakuchinone B obtained from the seeds of Alpinia oxyphylla, a member of the ginger family (Zingiberaceae), which are widely used as a folk remedy and as an anti-inflammatory. The aim of this study was to investigate the anti-arthritic effects of JC3 in rat models of carrageenan-induced paw pain and carrageenan/kaolin-induced knee arthritis. The anti-nociceptive effect of JC3 was assessed by measuring paw withdrawal pressure thresholds using an analgesy-meter. Arthritic symptoms in our monoarthritic rat model were evaluated using weight distribution ratios (WDR), paw thicknesses, and serum prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and vascular endothelial growth factor (VEGF) levels (determined by ELISA). Histological analyses of knee joints were performed after injecting JC3 intraperitoneally into rats before carrageenan treatment at 5 or 10 mg/kg/day for 6 days. The anti-inflammatory effects of JC3 were investigated in vitro using interleukin-1beta (IL-1β)-stimulated fibroblast-like synoviocytes (FLS) derived from arthritis patients. PGE2, IL-6, and IL-8 levels were measured after treating FLS with JC3. In arthritis-induced rats, JC3 treatment significantly decreased nociceptive and arthritic symptoms at days 5 to 6 after carrageenan/kaolin injection. Histological staining of knee tissue showed that JC3 significantly reduced inflammatory areas in the knee joints. Furthermore, JC3 inhibited the expressions of IL-6 and IL-8 in FLS cells at concentrations of 5–10 μg/ml and decreased PGE2 levels in FLS cells. These findings suggest JC3 has anti-arthritic effects in in vivo and in vitro, and that it might be useful for the treatment of arthritis.
- Published
- 2018
5. Effects of aromatic ring-substituted phenethylamines on the release of dopamine and serotonin
- Author
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Sooyeun Lee, Minjeong Kim, Chae Ha Yang, Seikwan Oh, Yong Sup Lee, and Choon-Gon Jang
- Subjects
biology ,Chemistry ,010401 analytical chemistry ,Biochemistry (medical) ,Phenethylamines ,Methamphetamine ,Nucleus accumbens ,Pharmacology ,Toxicology ,01 natural sciences ,0104 chemical sciences ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Monoamine neurotransmitter ,Dopamine ,medicine ,biology.protein ,030216 legal & forensic medicine ,Serotonin ,Serotonin transporter ,medicine.drug ,Dopamine transporter - Abstract
Significant disturbances of the classical amphetamines on the dopamine (DA) and serotonin (5-HT) systems have been previously reported. However, few studies have been conducted on the effects of new psychoactive phenethylamines on the release of DA and 5-HT. In the present study, the effects of new psychoactive phenethylamines with a variety of aromatic ring substitutions (5-API, 3-FMA, 5-MAPB, and DMMA) on the release of DA and 5-HT were investigated. Changes of DA, 5-HT and their metabolites in brain microdialysates from rats following exposure to the drugs were examined using a validated liquid chromatography–tandem mass spectrometry method. Their potencies of DA and 5-HT uptake inhibition as well as dopamine transporter (DAT) and serotonin transporter (SERT) binding were also determined. With the exception of DMMA, the drugs markedly affected the extracellular concentration of DA, 5-HT and/or their metabolites in rats and acted as potent inhibitors for DAT and/or SERT. Especially, 5-API potently induced the nonselective release of both DA and 5-HT, which was strongly correlated with a high degree of uptake inhibition and binding affinity to DAT and SERT. The 3-FMA, a methamphetamine analog with a halogen-substituted benzene, induced greater 5-HT release than DA. We found that new psychoactive phenethylamines, with a variety of aromatic ring substitutions, affected the extracellular levels of DA, 5-HT, and/or their metabolites in the nucleus accumbens of rats to varying degrees and in different ways. The current results may assist further research into monoamine neurotransmitter-related mechanisms of new psychoactive phenethylamines.
- Published
- 2018
6. Korean Red Ginseng and Ginsenoside-Rb1/-Rg1 Alleviate Experimental Autoimmune Encephalomyelitis by Suppressing Th1 and Th17 Cells and Upregulating Regulatory T Cells
- Author
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Seung-Yeol Nah, Byung-Joon Chang, Minhee Jang, Seikwan Oh, Byung Soo Chang, Sung-Hoon Kim, Jong Hwan Lee, Yi-Seong Kwak, Min Jung Lee, Do Young Kim, Jonghee Choi, and Ik-Hyun Cho
- Subjects
0301 basic medicine ,Chemokine ,Ginsenosides ,T-Lymphocytes, Regulatory ,Myelin ,0302 clinical medicine ,Medicine ,biology ,Experimental autoimmune encephalomyelitis ,FOXP3 ,Up-Regulation ,Platelet Endothelial Cell Adhesion Molecule-1 ,medicine.anatomical_structure ,Spinal Cord ,Neurology ,Blood-Brain Barrier ,Female ,Chemokines ,Neuroglia ,medicine.medical_specialty ,Encephalomyelitis, Autoimmune, Experimental ,T cell ,Neuroscience (miscellaneous) ,Panax ,Proinflammatory cytokine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Internal medicine ,Animals ,RNA, Messenger ,Inflammation ,Plant Extracts ,business.industry ,Macrophages ,Th1 Cells ,medicine.disease ,Oligodendrocyte ,Fibronectins ,Myelin basic protein ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Rats, Inbred Lew ,Chronic Disease ,Immunology ,biology.protein ,Th17 Cells ,business ,030217 neurology & neurosurgery ,Demyelinating Diseases - Abstract
The effects of Korean red ginseng extract (KRGE) on autoimmune disorders of the nervous system are not clear. We investigated whether KRGE has a beneficial effect on acute and chronic experimental autoimmune encephalomyelitis (EAE). Pretreatment (daily from 10 days before immunization with myelin basic protein peptide) with KRGE significantly attenuated clinical signs and loss of body weight and was associated with the suppression of spinal demyelination and glial activation in acute EAE rats, while onset treatment (daily after the appearance of clinical symptoms) did not. The suppressive effect of KRGE corresponded to the messenger RNA (mRNA) expression of proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin [IL]-1β), chemokines (RANTES, monocyte chemotactic protein-1 [MCP-1], and macrophage inflammatory protein-1α [MIP-1α]), adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and platelet endothelial cell adhesion molecule [PECAM-1]), and inducible nitric oxide synthase in the spinal cord after immunization. Interestingly, in acute EAE rats, pretreatment with KRGE significantly reduced the population of CD4(+), CD4(+)/IFN-γ(+), and CD4(+)/IL-17(+) T cells in the spinal cord and lymph nodes, corresponding to the downregulation of mRNA expression of IFN-γ, IL-17, and IL-23 in the spinal cord. On the other hand, KRGE pretreatment increased the population of CD4(+)/Foxp3(+) T cells in the spinal cord and lymph nodes of these rats, corresponding to the upregulation of mRNA expression of Foxp3 in the spinal cord. Interestingly, intrathecal pretreatment of rats with ginsenosides (Rg1 and Rb1) significantly decreased behavioral impairment. These results strongly indicate that KRGE has a beneficial effect on the development and progression of EAE by suppressing T helper 1 (Th1) and Th17 T cells and upregulating regulatory T cells. Additionally, pre- and onset treatment with KRGE alleviated neurological impairment of myelin oligodendrocyte glycoprotein(35-55)-induced mouse model of chronic EAE. These results warrant further investigation of KRGE as preventive or therapeutic strategies for autoimmune disorders, such as multiple sclerosis.
- Published
- 2015
7. Bergenin decreases the morphine-induced physical dependence via antioxidative activity in mice
- Author
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Jaesuk Yun, Kyunghwa Yun, Seikwan Oh, and Yeonju Lee
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Male ,Antioxidant ,NF-E2-Related Factor 2 ,Narcotic Antagonists ,medicine.medical_treatment ,Prefrontal Cortex ,Physical dependence ,Striatum ,Pharmacology ,medicine.disease_cause ,Antioxidants ,Translocation, Genetic ,Mice ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Benzopyrans ,Naloxone ,Organic Chemistry ,Bergenin ,Glutathione ,Substance Withdrawal Syndrome ,Mice, Inbred C57BL ,Liver ,chemistry ,Polyphenol ,Morphine ,Molecular Medicine ,medicine.symptom ,Morphine Dependence ,Heme Oxygenase-1 ,Oxidative stress ,medicine.drug - Abstract
Oxidative stress plays a role in the development of physical dependence induced by morphine. Bergenin, a polyphenol found in many Asian, African, and South American medicinal plants, is a potent antinarcotic agent with wide spectrum of pharmacological activities including antioxidant action. In the present study, we observed that bergenin decreased the development of physical dependence induced by morphine in mice and the antioxidant activity of bergenin plays a role in the antinarcotic effects through adapting to morphine-induced oxidative stress in the brain. The naloxone-precipitated withdrawal symptom (jumping frequency) was significantly ameliorated (50% of control group) by administration of bergenin (20 mg/kg) in morphine-treated mice. Furthermore, morphine-induced down-regulation of glutathione (GSH) contents was reversed by bergenin administration in the frontal cortex and liver. Bergenin had no effects on the increased levels of nfr2-dependent antioxidant enzyme HO1 and NQO1 in the frontal cortex, striatum, and liver of morphine-treated mice. However, the morphine-induced increase in nrf2 nuclear translocation in the frontal cortex and striatum was inhibited by bergenin treatment. These results suggest that bergenin has a potential antinarcotic effect via regulation of GSH contents and oxidative stress.
- Published
- 2014
8. A simple synthesis of trans-3,4,5-trimethoxycinnamamides and evaluation of their biologic activity
- Author
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Heena Lim, Dongguk Min, Mankil Jung, Sohyeon Moon, Jae Chul Jung, and Seikwan Oh
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Biochemistry ,Chemistry ,Stereochemistry ,Organic Chemistry ,Pharmacology toxicology ,Neurotoxicity ,medicine ,Biologic Evaluation ,General Pharmacology, Toxicology and Pharmaceutics ,Inhibitory postsynaptic potential ,Condensation reaction ,medicine.disease ,Coupling reaction - Abstract
A simple synthesis and biologic evaluation of trans-3,4,5-trimethoxycinnamamides 10a–e and 11 as novel antinarcotic agents is described. The synthetic key strategies involve condensation reaction and coupling reaction to generate trans-3,4,5-trimethoxycinnamamides 10a–e and 11. They were evaluated for free radical scavenging, inhibitory action for neurotoxicity in cultured neurons, and antinarcotic activity in mice. It was found that compounds 10a, 10d, and 10e displayed significant inhibitory action of the glutamate-induced neurotoxicity and 10a–e and 11 showed high antinarcotic activity in mice.
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- 2013
9. Simple synthesis and biological evaluation of flocoumafen and its structural isomers
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Oee Sook Park, Seikwan Oh, Soyong Jang, and Jae-Chul Jung
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chemistry.chemical_compound ,Column chromatography ,chemistry ,Flocoumafen ,Stereochemistry ,Intramolecular force ,Grignard reaction ,Structural isomer ,Knoevenagel condensation ,General Chemistry ,Coupling reaction ,Cis–trans isomerism - Abstract
Simple synthesis and biological properties of flocoumafen 1 and its structural isomers are described. The key synthetic strategies involve Knoevenagel condensation, Grignard reaction, intramolecular ring cyclization and coupling reaction. Flocoumafen 1 was easily separated into cis and trans forms using flash column chromatography. They were then evaluated for suppression of LPS-induced NO generation and anti-excitotoxicity in vitro. It was found that the trans-flocoumafen was potent suppressor of NO generation with the concentration of 10 µM in vitro, while no significant effect for neurotoxicity in cultured cortical neurons.
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- 2010
10. Alteration of sphingolipid metabolism and pSTAT3 expression by dietary cholesterol in the gallbladder of hamsters
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Yeonju Lee, Soyong Jang, Beom Jae Lee, Seikwan Oh, Yunsun Lee, Hyun Woo Shin, Jae Seon Kim, Hwan-Soo Yoo, Heena Lim, and Dong-Hyun Kim
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Male ,STAT3 Transcription Factor ,medicine.medical_specialty ,Nitric Oxide Synthase Type II ,Blood lipids ,Gallstones ,Biology ,Cholesterol, Dietary ,chemistry.chemical_compound ,Cricetinae ,Internal medicine ,Glial Fibrillary Acidic Protein ,Drug Discovery ,medicine ,Animals ,Sphingosine-1-phosphate ,Liver X receptor ,Sphingolipids ,Mesocricetus ,Cholesterol ,Organic Chemistry ,Reverse cholesterol transport ,Fatty liver ,Gallbladder ,medicine.disease ,Sphingolipid ,STAT1 Transcription Factor ,Endocrinology ,chemistry ,Low-density lipoprotein ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) - Abstract
Cholesterol and sphingolipids are major lipid constituents of the plasma membrane and have been implicated in a number of human diseases, such as atherosclerosis, fatty liver, diabetes mellitus, coronary heart disease, and hypertension. However, the relationship between cholesterol and sphingolipid metabolism has not been investigated. The purpose of this study was to determine whether dietary cholesterol would induce the alteration of sphingolipid metabolism in hamsters. Hypercholesterolemia was induced in hamsters by placing them on an experimental diet containing 0.5% cholesterol plus 0.5% choline chloride for 8 and 12 weeks. The serum profile of the hamsters showed that the administration of cholesterol increased the levels of total cholesterol, LDL cholesterol, and triglycerides as well as the activities of GOT and GPT. The levels of ceramide and sphingosine-1-phosphate (So-1-P) were remarkably elevated by 6-fold, respectively, in the bile juice of cholesterol-fed hamsters. Interestingly, the levels of iNOS and GFAP were increased in the gallbladders of cholesterol-fed hamsters. In addition, the immunostaining of pSTAT3 was increased on the gallbladder epithelium after cholesterol feeding. These results suggest that sphingolipid metabolism may be regulated in the bile juice during cholesterol feeding and may be a potential target for the treatment of hypercholesterolemia-induced diseases.
- Published
- 2009
11. Neuroprotective effect of benzylideneacetophenone derivative on the MPTP model of neurodegeneration in mice
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Jae Chul Jung, Seikwan Oh, Heena Lim, Jun Mo Kang, Soyong Jang, and Heejeong Kim
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Dopamine ,Blotting, Western ,Substantia nigra ,Striatum ,Pharmacology ,Neuroprotection ,Mice ,chemistry.chemical_compound ,Glial Fibrillary Acidic Protein ,Drug Discovery ,medicine ,Animals ,Dopamine transporter ,Neurons ,Dopamine Plasma Membrane Transport Proteins ,Propiophenones ,biology ,Tyrosine hydroxylase ,Chemistry ,MPTP ,Organic Chemistry ,Neurodegeneration ,MPTP Poisoning ,medicine.disease ,Immunohistochemistry ,Neostriatum ,Substantia Nigra ,Neuroprotective Agents ,medicine.anatomical_structure ,nervous system ,Biochemistry ,Cyclooxygenase 2 ,biology.protein ,Molecular Medicine ,Astrocyte - Abstract
In this study, we investigated the neuroprotective effect of a benzylideneacetophenone derivative, JC3, in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD). C57BL/6 mice were treated with MPTP (30 mg/kg, i.p.) for 5 consecutive days. JC3 (10 mg/kg, i.p.) treatment was initiated 2 h after the first administration of MPTP and then at 24-h intervals for 3 consecutive days. The mice were sacrificed for analyses 7 days after the last MPTP injection. Immunohistochemistry and Western blot were used to determine the expression levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), OX-42 (a marker of microglial activation), and glial fibrillary acid protein (GFAP, a marker of astrocyte activation) in the substantia nigra (SN) and striatum (ST). The results of these experiments demonstrated that JC3 restored the decreased TH-immunoreactivity (IR) and DAT and JC3 attenuated the increase in OX-42, GFAP, and COX-2 on the SN and ST on day 7 post-MPTP injection. These results suggest that JC3 can be a neuroprotective agent in an MPTP-induced model of PD.
- Published
- 2008
12. Endogenous sphingolipid metabolites related to the growth inSphingomonas chungbukensis
- Author
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Hwan-Soo Yoo, Youn Sun Lee, Jin Tae Hong, Munkhtsatsral Burenjargal, Yeo Pyo Yun, Young-Chang Kim, Yong-Moon Lee, Seikwan Oh, Youn Bok Chung, Dong Chul Moon, and Jae-Myung Yoo
- Subjects
Sphingolipids ,Time Factors ,biology ,Sphingosine ,Cell growth ,Organic Chemistry ,Hamster ,Endogeny ,Lipid signaling ,Bacterial growth ,biology.organism_classification ,Sphingomonas ,Sphingolipid ,Cell Line ,Cell biology ,chemistry.chemical_compound ,Biochemistry ,chemistry ,Cricetinae ,Insulin-Secreting Cells ,Drug Discovery ,Animals ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) ,Bacteria - Abstract
Sphingolipids are present in animals, plants, fungi, yeasts and some bacteria. In mammalian cells sphingolipids act as lipid mediators for cell growth, differentiation, apoptosis and angiogenesis. In contrast, in bacteria the biological significance of sphingolipids has not been fully elucidated and sphingolipid metabolism has not been investigated. The aim of this study was to compare the pattern of sphingolipid metabolites in HIT-T15 beta cells originating from hamster pancreas to that in the bacterial strain Sphingomonas chungbukensis DJ77, under various culture conditions. It was found that the concentration of cellular sphinganine (Sa) in S. chungbukensis was higher than that of sphingosine (So), while the level of cellular So in HIT-T15 cells was higher than that of Sa. Aeration and shaking during culture increased bacterial growth in S. chungbukensis, and the contents of So and Sa were also elevated. These results indicate that a de novo sphingolipid pathway appeared to be active in bacteria and that bacterial growth may be closely related to Sa levels.
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- 2007
13. Synthesis and evaluation of biological properties of benzylideneacetophenone derivatives
- Author
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Soyong Jang, Inn-Oc Han, Jae Chul Jung, Seikwan Oh, and Donghyun Kim
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Cell Survival ,Pharmacology toxicology ,Grignard reaction ,Glutamic Acid ,Cell Line ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Chalcone ,Picrates ,Diarylheptanoids ,Biological property ,Drug Discovery ,Animals ,Organic chemistry ,Cytotoxicity ,Scavenging ,Nitrites ,Cerebral Cortex ,Neurons ,Biphenyl Compounds ,Organic Chemistry ,Free Radical Scavengers ,In vitro ,Hydrazines ,Neuroprotective Agents ,chemistry ,Molecular Medicine ,Microglia - Abstract
A series of yakuchinone B 1f and its analogs 1a-e was synthesized and evaluated for free radical scavenging, suppression of LPS-induced NO generation, cytotoxicity and anti-excitotoxicity in vitro. Compound 1c exhibited potent anti-excitotoxicity, while all compounds 1a-f showed considerable effects of free radical scavenging, suppression of LPS-induced NO generation, and cytotoxicity in microglia.
- Published
- 2006
14. Protection of LLC-PK1 cells against hydrogen peroxide-induced cell death by modulation of ceramide level
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Hwan-Soo Yoo, Youn Sun Lee, Yeo Pyo Yun, Heon Kyo Choi, Seikwan Oh, Yong-Moon Lee, Jin Tae Hong, and Jae-Myung Yoo
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Ceramide ,Programmed cell death ,Swine ,Biology ,Ceramides ,medicine.disease_cause ,chemistry.chemical_compound ,Desipramine ,Drug Discovery ,medicine ,Animals ,Glutathione Transferase ,Sphingolipids ,Cell Death ,urogenital system ,Organic Chemistry ,Hydrogen Peroxide ,Glutathione ,Cytoprotection ,Molecular biology ,Acetylcysteine ,Cell biology ,Isoenzymes ,Oxidative Stress ,Sphingomyelin Phosphodiesterase ,Glutathione S-Transferase pi ,chemistry ,LLC-PK1 Cells ,Molecular Medicine ,Sphingomyelin ,Oxidative stress ,medicine.drug - Abstract
Oxidative stress has been reported to elevate ceramide level during cell death. The purpose of the present study was to modulate cell death in relation to cellular glutathione (GSH) level and GST (glutathione S-transferase) expression by regulating the sphingolipid metabolism. LLC-PK1 cells were treated with H2O2 in the absence of serum to induce cell death. Subsequent to exposure to H2O2, LLC-PK1 cells were treated with desipramine, sphingomyelinase inhibitor, and N-acetylcysteine (NAC), GSH substrate. Based on comparative visual observation with H2O2-treated control cells, it was observed that 0.5 microM of desipramine and 25 mM of NAC exhibited about 90 and 95% of cytoprotection, respectively, against H2O2-induced cell death. Desipramine and NAC lowered the release of LDH activity by 36 and 3%, respectively, when compared to 71% in H2O2-exposed cells. Cellular glutathione level in 500 microM H2O2-treated cells was reduced to 890 pmol as compared to control level of 1198 pmol per mg protein. GST P1-1 expression was decreased in H2O2-treated cells compared to healthy normal cells. In conclusion, it has been inferred that H2O2-induced cell death is closely related to cellular GSH level and GST P1-1 expression in LLC-PK1 cells and occurs via ceramide elevation by sphingomyelinase activation.
- Published
- 2005
15. Phorbol Ester Differentiates the Levels of [3H]MK-801 Binding in Rats Lines Selected for Differential Sensitivity to the Hypnotic Effects of Ethanol
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Chia-Yu Chang, Ing K. Ho, Seikwan Oh, and Rodney C. Baker
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Male ,Cerebellum ,medicine.medical_specialty ,medicine.drug_class ,Thalamus ,Biochemistry ,Rats, Sprague-Dawley ,Hypnotic ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Autoradiograph ,Species Specificity ,Internal medicine ,Image Interpretation, Computer-Assisted ,Phorbol Esters ,medicine ,Animals ,Hypnotics and Sedatives ,RNA, Messenger ,In Situ Hybridization ,Phorbol 12,13-Dibutyrate ,Protein Kinase C ,Protein kinase C ,Brain Chemistry ,Messenger RNA ,Ethanol ,Central Nervous System Depressants ,Rats, Inbred Strains ,General Medicine ,Rats ,medicine.anatomical_structure ,Endocrinology ,nervous system ,chemistry ,Autoradiography ,NMDA receptor ,Dizocilpine Maleate ,Excitatory Amino Acid Antagonists - Abstract
These studies addressed the possible involvement between sensitivity to the hypnotic action of ethanol and function of the NMDA receptor. The studies were carried out using high-alcohol sensitive (HAS) and low-alcohol sensitive (LAS) rats, two rats having differential sensitivity to the acute hypnotic action of ethanol. The animal models were developed by a selective breeding experiment. Using a quantitative autoradiograph technique, it was demonstrated that [3H]MK-801 binding to the NMDA receptor was highest in hippocampus in both HAS and LAS rats, but significant [3H]MK-801 binding was also detected in cortex, caudate-putamen, and thalamus of HAS and LAS rats. The density of [3H]MK-801 binding was lower only in cerebellar granule layers of untreated HAS rats as compared to the same brain area in untreated LAS rats. Activation of protein kinase C (PKC) by 100 nM PDBu, increased [3H]MK-801 binding in cortex, caudate-putamen, thalamus, central gray, and cerebellum of HAS rats but activation of PKC did not influence [3H]MK-801 binding in LAS rats. These activation of PKC differentiates between [3H]MK-801 binding of HAS and LAS rats in frontal cortex (layer II-IV and cingulate), caudate-putamen, and ventral lateral thalamic nuclei. The basal level of PKC-gamma mRNA was higher in HAS rats than that of LAS rats. These results suggest that the activation of PKC potentiates NMDA receptor function of the rat line which is more sensitive to alcohol (HAS) but does not affect [3H]MK-801 binding of alcohol resistant (LAS) rats.
- Published
- 2005
16. [Untitled]
- Author
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Hwa Kyung Lim, Dong Sup Kim, Soyong Jang, and Seikwan Oh
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medicine.medical_specialty ,Gs alpha subunit ,Forskolin ,Chemistry ,Butorphanol ,Gi alpha subunit ,General Medicine ,In situ hybridization ,Biochemistry ,Adenylyl cyclase ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Opioid ,Cerebral cortex ,Internal medicine ,medicine ,medicine.drug - Abstract
Butorphanol was infused continuously into cerebral ventricle at a constant rate of 26 nmol/μl/h for 3 days, and the withdrawal from opioid was rendered 7 h after the cessation of infusion. The G-protein α-subunit has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of G protein α-subunit mRNA were investigated by using in situ hybridization techniques. In situ hybridization showed marked changes in the levels of Gαs during butorphanol tolerance and withdrawal. Specifically, the level of Gαs mRNA was significantly decreased in almost all areas of brain except hippocampus during the butorphanol withdrawal. It was also decreased in the septum and cerebellar granule layer in butorphanol tolerant rats. The level of Gαi mRNA was significantly decreased only in the cerebral cortex of butorphanol tolerant rat. However, no such change was noted during the withdrawal from butorphanol. The level of Gαo mRNA was not changed either in butorphanol tolerant or in the butorphanol withdrawal rats. No alterations were noted in the level of [3H]forskolin binding to adenylyl cyclase in butorphanol tolerant as well as withdrawing rats. The levels of pCREB were significantly elevated in the hippocampus in the butorphanol withdrawal rats. These results suggest that region-specific changes of G protein α-subunit mRNA and pCREB without marked changes in the level of adenylyl cyclase may underlie the tolerance to and withdrawal from butorphanol.
- Published
- 2003
17. [Untitled]
- Author
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Seikwan Oh and Seung Yeol Nah
- Subjects
medicine.medical_specialty ,Messenger RNA ,Cerebellum ,Gs alpha subunit ,Chemistry ,G protein ,Central nervous system ,General Medicine ,In situ hybridization ,Biochemistry ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,medicine.anatomical_structure ,Endocrinology ,Ginsenoside ,Internal medicine ,medicine ,Hippocampus (mythology) - Abstract
We have investigated the effects of centrally administered ginsenoside Rc and Rg1 on the modulation of G protein expression in the central nervous system in rat brain. The effects of continuous infusion of ginsenosides on the modulation of G protein α-subunit mRNA were investigated by using in situ hybridization study. Rats were infused with ginsenoside Rc or Rg1 (10 μg/10 μl/h, i.c.v.) for 7 days, through preimplanted cannula by osmotic minipumps. The level of Gαs mRNA was not changed by the infusion of ginsenoside Rc or Rg1. The level of Gai mRNA was significantly elevated in frontal cortex and hippocampus following treatment with ginsenoside Rc as well as ginsenoside Rg1. However, the level of Gαo mRNA was significantly decreased in part of the hippocampus and cerebellum after the animals had received ginsenoside Rg1 infusion. These results suggest that prolonged infusion of ginsenosides could differentially modulate the expression of G protein α-subunit mRNA in rat brain in a region-specific manner.
- Published
- 2003
18. [Untitled]
- Author
-
So Yong Jang, Younghwa Kim, and Seikwan Oh
- Subjects
Butorphanol ,GABAA receptor ,Glutamate decarboxylase ,Hippocampus ,General Medicine ,Pharmacology ,Biochemistry ,Cortex (botany) ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,nervous system ,Opioid ,Muscimol ,chemistry ,medicine ,Flunitrazepam ,psychological phenomena and processes ,medicine.drug - Abstract
We have investigated the effects of continuous infusion of butorphanol on the modulation of GABAA receptor binding. Butorphanol was infused continuously into intracerebroventricle (ICV) at a constant rate of 26 nmol/μl/h for 3 days, and the withdrawal from opioid was rendered 7 h after the cessation of infusion. The GABAA receptor bindings in rat brain slices were analyzed by quantitative autoradiography using [3H]muscimol and [3H]flunitrazepam. In the rats withdrawn from butorphanol, the levels of [3H]muscimol binding were significantly elevated in cortex, thalamus, and part of the hippocampus. The levels of [3H]flunitrazepam binding were elevated in almost all of brain regions including cortex, caudate putamen, thalamus, hippocampus, brainstem, and cerebellum in the rats withdrawn from butorphanol. The levels of binding of either [3H]muscimol or [3H]flunitrazepam were not changed in the rats tolerant to butorphanol. However, the activity of GABAergic neuron was not found to have been modulated by butorphanol withdrawal, because the level of glutamic acid decarboxylase was not changed markedly either in rats that were tolerant to or withdrawn from butorphanol by Western blot and immunohistochemical data. These results suggest that the withdrawal from butorphanol infusion markedly elevates the binding of [3H]muscimol and [3H]flunitrazepam throughout the brain in a region-specific manner, and that the regulatory mechanisms in butorphanol tolerance and withdrawal may be different.
- Published
- 2002
19. [Untitled]
- Author
-
Seikwan Oh and Younghwa Kim
- Subjects
medicine.medical_specialty ,Messenger RNA ,Pentobarbital ,Chemistry ,G protein ,Alpha (ethology) ,General Medicine ,In situ hybridization ,Pharmacology ,Biochemistry ,Cellular and Molecular Neuroscience ,Endocrinology ,Drug tolerance ,Internal medicine ,medicine ,Systemic administration ,Drug metabolism ,medicine.drug - Abstract
Pentobarbital was continuously infused intracerebroventricularly (i.c.v.) at the rate of 300 micrograms/10 microliters/h for 7 days, and withdrawal from pentobarbital was rendered 24 h after the stopping of the infusion. To eliminate the induction of hepatic metabolism by systemic administration of pentobarbital, an i.c.v. infusion model of tolerance to and withdrawal from pentobarbital was used. Little is known about the functional modulation of the G protein alpha-subunits at the molecular level. The effects of continuous infusion of pentobarbital on the modulation of G protein alpha-subunits mRNA were investigated by using in situ hybridization study. In situ hybridization showed that the level of G alpha s mRNA was increased in the septum and brainstem, and the level of G alpha o mRNA was elevated in the cortex during the pentobarbital withdrawal. The level of G alpha i mRNA was significantly elevated in almost all area of brain during the pentobarbital withdrawal. These results suggest that region-specific changes of G protein alpha-subunit mRNA were involved in the withdrawal from pentobarbital, whereas alpha-subunit is not so highly involved in the pentobarbital tolerance.
- Published
- 2002
20. [Untitled]
- Author
-
Ing Kang Ho, Seikwan Oh, Young Hwa Kim, Hong Serck Choi, Hee Lai Lee, Hack-Seang Kim, and Hoo Jae Hann
- Subjects
medicine.medical_specialty ,Cerebellum ,Dentate gyrus ,Central nervous system ,General Medicine ,Striatum ,In situ hybridization ,Biology ,Biochemistry ,Dizocilpine ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Cerebral cortex ,Internal medicine ,medicine ,NMDA receptor ,medicine.drug - Abstract
The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 μl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.
- Published
- 2001
21. [Untitled]
- Author
-
Seikwan Oh, Ing K. Ho, Joo-Il Kim, and Myeon-Woo Chung
- Subjects
medicine.medical_specialty ,Chemistry ,Butorphanol ,musculoskeletal, neural, and ocular physiology ,Dentate gyrus ,Glutamate receptor ,Hippocampus ,General Medicine ,Granule cell ,Biochemistry ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Cerebral cortex ,Internal medicine ,medicine ,NMDA receptor ,Receptor ,medicine.drug - Abstract
The NMDA receptor has been implicated in opioid tolerance and withdrawal. The effects of continuous infusion of butorphanol on the modulation of NMDA receptor subunit NR1, NR2A, NR2B, and NR2C gene expression were investigated by using in situ hybridization technique. Continuous intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/microl/h) resulted in significant modulations in the NRI, NR2A, and NR2B mRNA levels. The level of NR1 mRNA was significantly decreased in the cerebral cortex, thalamus, and CA1 area of hippocampus in butorphanol tolerant and withdrawal (7 h after stopping the infusion) rats. The NR2A mRNA was significantly decreased in the CA1 and CA3 of hippocampus in tolerant rats and increased in the cerebral cortex and dentate gyrus in butorphanol withdrawal rats. NR2B subunit mRNA was decreased in the cerebral cortex, caudate putamen, thalamus, CA3 of hippocampus in butorphanol withdrawal rats. No changes of NR1, NR2A, NR2C subunit mRNA in the cerebellar granule cell layer were observed in either butorphanol tolerant or withdrawal rats. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased significantly in all brain regions except in the thalamus and hippocampus, at the 7 hr after stopping the butorphanol infusion. These results suggest that region-specific changes of NMDA receptor subunit mRNA (NR1 and NR2) as well as NMDA receptor binding ([3H]MK-801) are involved in the development of tolerance to and withdrawal from butorphanol.
- Published
- 2000
22. [Untitled]
- Author
-
Ing K. Ho and Seikwan Oh
- Subjects
medicine.medical_specialty ,Pentobarbital ,Cerebellum ,medicine.drug_class ,GABAA receptor ,General Medicine ,Biochemistry ,Hypnotic ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Muscimol ,chemistry ,Barbiturate ,Drug tolerance ,Internal medicine ,medicine ,Receptor ,medicine.drug - Abstract
Effects of continuous pentobarbital administration on binding characteristics of [3H]muscimol were examined by autoradiography, and levels of GABAA receptor β2-subunit mRNA were investigated by in situ hybridization histochemistry in the rat brain. In order to eliminate the induction of hepatic metabolism by systemic administration of pentobarbital, an i.c.v. infusion model of tolerance to and withdrawal from pentobarbital was used. An experimental model of barbiturate tolerance and withdrawal was developed using i.c.v. infusion of pentobarbital (300 μg/10 μl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from pentobarbital. The levels of [3H]muscimol binding were elevated in cingulate of frontal cortex (46%) and granule layer of cerebellum (32%) of rats 24-hr after withdrawal from pentobarbital, while it was only elevated in cingulate (58%) of tolerant rats. The GABAA receptor β2-subunit mRNA was increased in the withdrawal rats only: in the cortex (9–14%), hippocampus (15–21%), inferior colliculus (21%), and granule layer of cerebellum (24%). These results show the involvement of GABAA receptor and its β2-subunit up-regulations in pentobarbital withdrawal rats, and suggest that the levels of [3H]muscimol binding and GABAA receptor β2-subunit mRNA are altered in a region-specific manner during pentobarbital withdrawal.
- Published
- 1999
23. [Untitled]
- Author
-
Choon-Gon Jang, Ing Kang Ho, and Seikwan Oh
- Subjects
medicine.medical_specialty ,Pentobarbital ,medicine.drug_class ,Central nervous system ,Glutamate receptor ,Hippocampus ,General Medicine ,In situ hybridization ,Biology ,Biochemistry ,Hypnotic ,Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Endocrinology ,nervous system ,Internal medicine ,Gene expression ,medicine ,NMDA receptor ,medicine.drug - Abstract
Little is known about the functional modulation of NMDA receptor subunits at the molecular level. Therefore, a series of experiments were conducted to elucidate more fully the role of NMDA receptor subtypes in pentobarbital tolerance and withdrawal. We investigated the influence of centrally administered pentobarbital on the regulation of mRNA levels of the family of NMDA receptor 2 (NR2) subtypes (NR2A, NR2B, and NR2C) by in situ hybridization histochemistry in rat brain. Animals were rendered tolerant by continuous intracerebroventricular (i.c.v.) infusion with pentobarbital (300 μg/10 μl/hr for 6 days) through pre-implanted cannulae connected to osmotic mini-pumps, and dependent, by abrupt withdrawal from pentobarbital. The NR2A subunit mRNA was increased in cortical areas in pentobarbital tolerant and withdrawal rats. In contrast, the NR2B mRNA was decreased in parietal cortex and hippocampus in both tolerance and withdrawal rats. The level of NR2C mRNA was increased in withdrawal rats, while there was no change in tolerant rats. These results indicate that continuous i.c.v. infusion with pentobarbital alters NR2 subunit mRNA expression in the rat brain, suggesting that NR2 subunits may play an important role in the development of tolerance to and withdrawal from pentobarbital.
- Published
- 1998
24. [Untitled]
- Author
-
Susan E. Wellman, Seikwan Oh, and Ing K. Ho
- Subjects
medicine.medical_specialty ,Pentobarbital ,Forskolin ,Chemistry ,medicine.drug_class ,Dentate gyrus ,Adenylate kinase ,Physical dependence ,General Medicine ,Hippocampal formation ,Biochemistry ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Endocrinology ,nervous system ,Barbiturate ,Internal medicine ,medicine ,medicine.symptom ,Protein kinase C ,medicine.drug - Abstract
These studies were designed to examine the effect of chronic administration of pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in the rat brain by autoradiography. Recently, it has been suggested that the phosphorylation of specific proteins may be involved in the development of physical dependence. An experimental model of barbiturate tolerance and dependence was developed using i.c.v. infusion of pentobarbital (300 μg/ 10 μl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from pentobarbital. The levels of [3H]forskolin binding were elevated (28–67%) in cortex, thalamus, dentate gyrus, hippocampal CA3 and cerebellum of the pentobarbital withdrawal animals, while these changes were not observed in tolerant rats. The levels of [3H]phorbol dibutyrate binding were highly elevated (38–65%) in the region of cortex, caudate putamen, septum, thalamus, dentate gyrus, and cerebellum of rats withdrawal from pentobarbital. These results show that the levels of AC and PKC were significantly elevated in pentobarbital withdrawal rats, and suggest that the levels of AC and PKC are altered in a region-specific manner during pentobarbital withdrawal.
- Published
- 1998
25. [Untitled]
- Author
-
Ing Kang Ho, Katsuji Hoshi, and Seikwan Oh
- Subjects
Hyperthermia ,medicine.medical_specialty ,Pentobarbital ,Chemistry ,medicine.drug_class ,Central nervous system ,Glutamate receptor ,General Medicine ,medicine.disease ,Biochemistry ,Cellular and Molecular Neuroscience ,Endocrinology ,medicine.anatomical_structure ,Barbiturate ,Internal medicine ,medicine ,NMDA receptor ,Righting reflex ,Tolerance dependence ,medicine.drug - Abstract
Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK-801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μl/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK-801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.
- Published
- 1997
26. Effects of oxygen free radicals on extracellular glutamate accumulation in cultured cells
- Author
-
Hack-Seang Kim, Myung Koo Lee, Seikwan Oh, Ki Wan Oh, and Chang Sik Shin
- Subjects
biology ,Chemistry ,Radical ,Organic Chemistry ,Glutamate receptor ,Kainate receptor ,Calcium in biology ,Superoxide dismutase ,chemistry.chemical_compound ,medicine.anatomical_structure ,nervous system ,Biochemistry ,Pyrogallol ,Drug Discovery ,medicine ,biology.protein ,Biophysics ,Molecular Medicine ,NMDA receptor ,Astrocyte - Abstract
Exogenously applied oxygen free radical generating agent, pyrogallol, highly elevated extracellular glutamate accumulation and augmented N-methyl-D-aspartate (NMDA)-induced glutamate accumulation in cerebellar granule neuronal cells, but did not in astrocytes. Superoxide dismutase remarkably decreased the pyrogallol-induced glutamate accumulation, but either NMDA or kainate antagonists did not. In addition, pyrogallol did not affect the NMDA-induced intracellular calcium elevation. Pyrogallol partially blocked glutamate uptake into astrocytes. These results suggest that oxygen free radicals elevate extracellular glutamate accumulation by stimulating the release of glutamate as well as blocking the glutamate uptake.
- Published
- 1996
27. Kainate-induced elevations of intracellular Ca2+ and extracellular glutamate are partially decreased by NMDA receptor antagonists in cultured cerebellar granule neurons
- Author
-
Patrick P. McCaslin, Seikwan Oh, and Shogo Tokuyama
- Subjects
Membrane potential ,medicine.medical_specialty ,Chemistry ,Organic Chemistry ,Granule (cell biology) ,Glutamate receptor ,Kainate receptor ,AMPA receptor ,Endocrinology ,nervous system ,Biochemistry ,Internal medicine ,Drug Discovery ,medicine ,Molecular Medicine ,NMDA receptor ,Receptor ,Intracellular - Abstract
Several lines of evidence indicate that physiological activity of N-methyl-D-aspartate (NMDA) receptor was blocked by physiological concentration of Mg2+ (1.2 mM). However, the activity of NMDA receptor may not be blocked totally with this concentration of Mg2+ under elevated membrane potential by kainate. Here, we described the effect of Mg2+ on NMDA receptor and how much of NMDA receptor functions could be activated by kainate. Effects of NMDA receptor antagonist on kainate-induced elevation of intracellular Ca2+ levels ([Ca2+]i) and extracellular glutamate level were examined in cultured rat cerebellar granule neurons. Kainate-induced elevation of [Ca2+]i was not affected by physiological concentration of Mg2+ though NMDA-induced elevation was blocked by the same concentration of Mg2+. Kainate-induced elevation of [Ca2+]i was decreased by 32% in the presence of NMDA antagonists, MK-801 and CPP (3-[2-carboxypiperazine-4-yl]propyl-1-phosphonic acid), in Mg2+ free buffer. Kainate receptor-activated glutamate release was also decreased (30%) by MK-801 or CPP. These results show that certain extent of elevations of intracellular Ca2+ and extracellular glutamate by kainate is due to coactivation of NMDA receptors.
- Published
- 1995
28. Effects of ginsenosides on the glutamate release and intracellular calcium levels in cultured rat cerebellar neuronal cells
- Author
-
Seikwan Oh, Hack-Seang Kim, and Yeon Hee Seong
- Subjects
Chemistry ,Organic Chemistry ,Drug Discovery ,Granule (cell biology) ,Pharmacology toxicology ,Glutamate receptor ,Molecular Medicine ,NMDA receptor ,Pharmacology ,Neurotransmission ,Homeostasis ,Calcium in biology - Abstract
These studies were designed to examine the effects of ginsenosides on glutamate neurotransmission. In primary cultures of rat cerebellar granule cells, ginsenosides (Rb1, Rc and Rg1, 500 μg/ml) increased glutamate release which was measured by HPLC, but Re did not show an elevation of glutamate release. However, all of these ginsenosides down-regulated N-methyl-D-aspartate (NMDA)-induced glutamate release. Rc strongly increased glutamate release and elevated intracellular calcium concentrations (Ca2+i) which was measured by ratio fluorometry with FURA-2 AM. These, results indicate that ginsenosides have a homeostatic effect on glutamate neurotransmission, and there is a structure-function relationship among the ginsenosides tested.
- Published
- 1995
29. The time course of NMDA-and kainate-induced cGMP elevation and glutamate release in cultured neuron
- Author
-
Seikwan Oh, Chang Sik Shin, and Hack-Seang Kim
- Subjects
Agonist ,medicine.medical_specialty ,Chemistry ,medicine.drug_class ,Organic Chemistry ,Antagonist ,Glutamate receptor ,Kainate receptor ,Receptor antagonist ,chemistry.chemical_compound ,Endocrinology ,Biochemistry ,Internal medicine ,Drug Discovery ,medicine ,DNQX ,Molecular Medicine ,NMDA receptor ,Phencyclidine ,medicine.drug - Abstract
The levels of extracellular glutamate, intracellular Ca2+ ([Ca2+]i) and cGMP were determined for 1 h with the excitatory amino acids, N-methyl-D-aspartate (NMDA) or kainate in cultured cerebellar granule cells. Both NMDA and kainate produced a time-dependent release of glutamate, and kainate was more potent than NMDA in glutamate elevation. The elevation of extracellular glutamate was not purely governed by intracellular Ca2+ concentration. However, in opposite to the time-dependent elevation of glutamate, the elevation of cGMP by NMDA and kainate were at maximum level in short-time (1 min) incubation then remarkably decreased with longer incubation times. Post-applications (30 min after agonist) of EAA antagonst did not block EAAs-induced glutamate elevation. However, NMDA antagonist, phencyclidine (PCP), blocked NMDA-induced cGMP elevation at pre- or post-application, but kainate antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX), paradoxically augmented kainate-induced cGMP elevation for 1 h incubation. These results show that NMDA or kainate induces time-dependent elevations of extracellular glutamate, while the elevations of cGMP by these EAAs are remarkably decreased with longer incubation times. However, NMDA- and kainate-induced glutamate release was blocked by pre-application of each receptor antagonist but not by post-application while EAA-induced [Ca2+]i was blocked by post-application of antagonist. These observations suggest that EAA-induced elevation of [Ca2+]i is not parallel with elevation of glutamate release or cGMP.
- Published
- 1995
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