19 results on '"Yasuyoshi H"'
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2. Superior oblique paresis with contralateral relative afferent pupillary defect
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Taguchi, H., Kashii, S., Kikuchi, M., Yasuyoshi, H., and Honda, Y.
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- 2000
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3. Development of a contacting transwell co-culture system for the in vitro propagation of primary central nervous system lymphoma
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Mayuko Nishi, Kensuke Tateishi, Jeremiah Stanleyraj Sundararaj, Yoko Ino, Yusuke Nakai, Yasuyoshi Hatayama, Yutaro Yamaoka, Yusaku Mihana, Kei Miyakawa, Hirokazu Kimura, Yayoi Kimura, Tetsuya Yamamoto, and Akihide Ryo
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PCNSL ,lymphoma ,vitrigel ,pericytes ,HGF ,Pin1 ,Biology (General) ,QH301-705.5 - Abstract
Primary central nervous system lymphoma (PCNSL) is a malignant neoplasm of the central nervous system that is refractory to treatment and has extremely poor prognosis. One factor hindering the development of therapeutic options for PCNSL is its molecular heterogeneity and the extreme difficulty in establishing in vitro cell lines that permit intensive research on this disease. In the present study, we developed a method to propagate PCNSL cells in vitro using a contacting transwell cell culture system involving brain vascular pericytes. The co-culture system was found to recapitulate the tumor microenvironment that is influenced by the biological activity of adjacent pericytes, and to sustain the survival and proliferation of PCNSL cells in vitro. We further delineated the underlying molecular mechanisms and found that the HGF–c-Met axis may be involved in the long-term in vitro culture of PCNSL cells. Moreover, the peptidylprolyl isomerase Pin1 was found to play a key role in PCNSL cell survival and it sustained proliferation through interactions with key transcription factors related to B-cell lymphomagenesis. These results suggest that our in vitro co-culture system is well suited to analyzing the biological and molecular characteristics of PCNSL, and may contribute to the discovery of new therapeutic interventions.
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- 2023
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4. Therapeutic effects of KRM-II-81, positive allosteric modulator for α2/3 subunit containing GABAA receptors, in a mouse model of Dravet syndrome
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Sachiko Nakakubo, Yasuyoshi Hiramatsu, Takeru Goto, Syuhei Kimura, Masashi Narugami, Midori Nakajima, Yuki Ueda, Hideaki Shiraishi, Atsushi Manabe, Dishary Sharmin, James M. Cook, and Kiyoshi Egawa
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Dravet syndrome ,mouse model ,antiseizure ,positive allosteric modulator for α2/3 subunit containing GABA A receptor ,anxiolytics ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Introduction: Dravet syndrome (DS) is an intractable epilepsy syndrome concomitant with neurodevelopmental disorder that begins in infancy. DS is dominantly caused by mutations in the SCN1A gene, which encodes the α subunit of a voltage-gated Na channel. Pre-synaptic inhibitory dysfunction is regarded as the pathophysiological mechanism, but an effective strategy for ameliorating seizures and behavioral problems is still under development. Here, we evaluated the effects of KRM-II-81, a newly developed positive allosteric modulator for α 2/3 subunit containing GABAA receptors (α2/3-GABAAR) in a mice model of DS both in vivo and at the neuronal level.Methods: We used knock-in mice carrying a heterozygous, clinically relevant SCN1A mutation (background strain: C57BL/6 J) as a model of the DS (Scn1aWT/A1783V mice), knock-in mouse strain carrying a heterozygous, clinically relevant SCN1A mutation (A1783V). Seizure threshold and locomotor activity was evaluated by using the hyperthermia-induced seizure paradigm and open filed test, respectively. Anxiety-like behavior was assessed by avoidance of the center region in locomotor activity. We estimated a sedative effect by the total distance traveled in locomotor activity and grip strength. Inhibitory post synaptic currents (IPSCs) were recorded from a hippocampal CA1 pyramidal neuron in an acutely prepared brain slice.Results: KRM-II-81 significantly increased the seizure threshold of Scn1aWT/A1783V mice in a dose-dependent manner. A low dose of KRM-II-81 specifically improved anxiety-like behavior of Scn1aWT/A1783V mice. A sedative effect was induced by relatively high dose of KRM-II-81 in Scn1aWT/A1783V mice, the dose of which was not sedative for WT mice. KRM-II-81 potentiated IPSCs by increasing its decay time kinetics. This effect was more prominent in Scn1aWT/A1783V mice.Discussion: Higher activation of α2/3-GABAAR by KRM-II-81 suggests a compensatory modification of post synaptic inhibitory function against presynaptic inhibitory dysfunction in Scn1aWT/A1783V. The increased sensitivity for KRM-II-81 may be relevant to the distinct dose-dependent effect in each paradigm of Scn1aWT/A1783V mice.Conclusion: Selective activation for α2/3-GABAAR by KRM-II-81 could be potential therapeutic strategy for treating seizures and behavioral problems in DS.
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- 2023
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5. An autopsy case of COVID-19-like acute respiratory distress syndrome after mRNA-1273 SARS-CoV-2 vaccination.
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Yukihiro Yoshimura, Hiroaki Sasaki, Nobuyuki Miyata, Kazuhito Miyazaki, Koji Okudela, Yoko Tateishi, Hiroyuki Hayashi, Ai Kawana-Tachikawa, Hiromichi Iwashita, Kazuho Maeda, Yoko Ihama, Yasuyoshi Hatayama, Akihide Ryo, and Natsuo Tachikawa
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COVID-19 ,vaccine ,acute respiratory distress syndrome ,autopsy ,Infectious and parasitic diseases ,RC109-216 - Abstract
We report the first case with COVID-19-like acute respiratory distress syndrome after mRNA-1273 SARS-CoV-2 vaccination. An 88-year-old woman developed dyspnea several hours after vaccination with the second dose of mRNA-1273. She was hospitalized on day nine due to worsening dyspnea. Chest computed tomography showed bilateral ground-glass opacities and consolidations, mainly in the peripheral lung areas. Repeat polymerase chain reaction tests for SARS-CoV-2 were negative, although the serum level of antibodies against spike protein was extremely elevated. Her condition did not improve with high-dose corticosteroids and high-flow nasal cannula oxygen therapy; she died on day 18. Autopsy findings revealed very early-phase diffuse alveolar damage in the whole lung without other lung diseases. The clinical and pathological findings suggested vaccine-induced acute respiratory distress syndrome. Serological and pathological tests might be useful to differentiate the disease from COVID-19.
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- 2022
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6. Generation and Utilization of a Monoclonal Antibody against Hepatitis B Virus Core Protein for a Comprehensive Interactome Analysis
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Yusuke Nakai, Kei Miyakawa, Yutaro Yamaoka, Yasuyoshi Hatayama, Mayuko Nishi, Hidefumi Suzuki, Hirokazu Kimura, Hidehisa Takahashi, Yayoi Kimura, and Akihide Ryo
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Hepatitis B virus ,monoclonal antibody ,antibody-based in situ biotinylation ,interactome analysis ,hypoxia ,Biology (General) ,QH301-705.5 - Abstract
Hepatitis B virus (HBV) core antigen (HBc) is a structural protein that forms the viral nucleocapsid and is involved in various steps of the viral replication cycle, but its role in the pathogenesis of HBV infection is still elusive. In this study, we generated a mouse monoclonal antibody (mAb) against HBc and used it in antibody-based in situ biotinylation analysis in order to identify host proteins that interact with HBc. HBc antigen was produced with a wheat germ cell-free protein synthesis system and used to immunize mice. Among the established hybridoma clones, a single clone (mAb #7) was selected and further characterized for its ability in the antibody-based in situ biotinylation analysis to collect host proteins that are in the vicinity of HBc. Using mass spectrometry, we identified 215 HBc-interacting host proteins, three of which bind HBc most significantly under hypoxic conditions. Our results indicate that mAb #7 can be used to systematically identify host proteins that interact with HBc under pathophysiological conditions, and thus may be useful to explore the molecular pathways involved in HBV-induced cytopathogenesis.
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- 2022
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7. Prospective Clinical Evaluation of the Diagnostic Accuracy of a Highly Sensitive Rapid Antigen Test Using Silver Amplification Technology for Emerging SARS-CoV-2 Variants
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Kazuaki Obata, Kei Miyakawa, Toshiki Takei, Atsuhiko Wada, Yasuyoshi Hatayama, Hideaki Kato, Yayoi Kimura, Hisakuni Sekino, Junichi Katada, and Akihide Ryo
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SARS-CoV-2 ,COVID-19 ,rapid antigen test ,diagnostic performance study ,Biology (General) ,QH301-705.5 - Abstract
The COVID-19 pandemic caused by SARS-CoV-2 remains a serious health concern worldwide due to outbreaks of SARS-CoV-2 variants that can escape vaccine-acquired immunity and infect and transmit more efficiently. Therefore, an appropriate testing method for COVID-19 is essential for effective infection control and the prevention of local outbreaks. Compared to reverse-transcription polymerase chain reaction (RT-PCR) tests, antigen tests are used for simple point-of-care testing, enabling the identification of viral infections. In this study, we tested the clinical usefulness of the FUJIFILM COVID-19 Ag test, an antigen test based on silver amplification and immunochromatographic technology. The FUJIFILM COVID-19 Ag test was shown to detect a lower viral concentration as compared to other conventional kits without significant performance loss in detecting prevalent SARS-CoV-2 variants. We tested nasopharyngeal and nasal swabs from a single patient during two different epidemic periods dominated by various SARS-CoV-2 variants. We observed that the sensitivity of the FUJIFILM COVID-19 Ag test was 95.7% and 85.7% in nasopharyngeal and nasal swabs, respectively. These results suggest that the FUJIFILM COVID-19 Ag test is highly sensitive and applicable when RT-PCR testing is unavailable. Furthermore, these results indicate that high-frequency testing using nasal swab specimens may be a valuable screening strategy.
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- 2022
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8. Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy
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Yasuyoshi Hatayama, Yutaro Yamaoka, Takeshi Morita, Sundararaj Stanleyraj Jeremiah, Kei Miyakawa, Mayuko Nishi, Yayoi Kimura, Makoto Mitsunaga, Tadayuki Iwase, Hirokazu Kimura, Naoki Yamamoto, Akifumi Takaori-Kondo, Hideki Hasegawa, and Akihide Ryo
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HTLV-1 ,monoclonal antibody ,near infrared photoimmuno-antimicrobial strategy ,IR700 ,Microbiology ,QR1-502 - Abstract
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, causes adult T-cell leukemia-lymphoma, HTLV-1 associated myelopathy/tropical spastic paraparesis, and HTLV-1 uveitis. Currently, no antiretroviral therapies or vaccines are available for HTLV-1 infection. This study aimed to develop an antibody against the HTLV-1 envelope protein (Env) and apply it to a near-infrared photoimmuno-antimicrobial strategy (NIR-PIAS) to eliminate HTLV-1 infected cells. We established mouse monoclonal antibodies (mAbs) against HTLV-1 Env by immunization with a complex of liposome and the recombinant protein. Detailed epitope mapping revealed that one of the mAbs bound to the proline-rich region of gp46 and exhibited no obvious neutralizing activity to inhibit viral infection. Instead, the mAb was rarely internalized intracellularly and remained on the cell surface of HTLV-1-infected cells. The antibody conjugated to the photosensitive dye IRDye700Dx recognized HTLV-1 infected cells and killed them following NIR irradiation. These results suggest that the novel mAb and NIR-PIAS could be developed as a new targeted therapeutic tool against HTLV-1 infected cells.
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- 2022
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9. Variation of 2-Acetyl-1-Pyrroline Concentration in Aromatic Rice Grains Collected in the Same Region in Japan and Factors Affecting Its Concentration
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Tomio Itani, Masahiko Tamaki, Yasuyoshi Hayata, Tsutomu Fushimi, and Katsumi Hashizume
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Aromatic rice ,Harvest time ,Oryza sativa L. ,2-Acetyl-1-pyrroline ,Temperature ,Variation ,Plant culture ,SB1-1110 - Abstract
Aroma strength of aromatic rice varies with the genetic and environmental conditions. We determined the concentration of 2-acetyl-1-pyrroline (2AP), a key compound of the aroma of aromatic rice, in 62 samples of rice grains (brown rice) from‘Hieri’ produced by 17˜24 farmers in 3 years in the Kubokawa area of Kochi Prefecture, Japan. Many ofthem showed similar values and the standard deviations were 27˜31%. However, a few samples showed extremely high (200%) or low (60%) 2AP concentrations compared to the individual year averages (100%). The influence of harvest time and temperature during ripening on the 2AP concentration in the brown rice was also examined using two cultivars. During grain development in an early-heading cultivar ‘Miyakaori’ , the 2AP concentration in the brown rice reached a peakat 4 or 5 weeks after heading (WAH) and then decreased rapidly to 20% of the maximum at 7 or 8 WAH. In a late-heading cultivar ‘Hieri’, the 2AP concentration peaked at 4 WAH then gradually decreased to 40% of the maximum at 8 WAH.The 2AP concentration was higher in brown rice ripened at a low temperature (day : 25°C/night : 20°C) than that ripened at a high temperature (day: 35°C/night: 30°C) in both a short-grain cultivar ‘Hieri’ and a long-grain cultivar ‘Sari Queen’.
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- 2004
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10. Ultrastructure of cranial nerves of rats inoculated with rabies virus Ultraestrutura de nervos cranianos de ratos inoculados com o vírus da raiva
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Guilberto Minguetti, Robin M. Hofmeister, Yasuyoshi Hayashi, and Juan A. Montaño
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raiva ,nervos cranianos ,microscopia eletrônica ,rabies ,cranial nerves ,electron microscopy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
The V and VII cranial nerves of rats inoculated with rabies virus were studied by electron microscopy. The results were compared with the same cranial nerves of rats inoculated with rabies virus but vaccinated against the disease. The findings are those of axonal degeneration and intense demyelination of the nerves of the group of rats not vaccinated. The vaccinated rats showed some ultrastructural irrelevant alterations when compared with the other group. The degree of ultrastructural alterations found in the group of rats not vaccinated suggests that in rabies severe damage of the cranial nerves occurs and that this may be closely related to the clinical picture of the disease (hydrophobia). Furthermore, as far as the authors know, this has not been considered in the classic descriptions of rabies and it is possible that an immunologic process may take part in the demyelination observed in the present study.Os autores estudaram o quinto e o sétimo nervos cranianos de ratos inoculados com o vírus da raiva. Os resultados foram comparados com os mesmos nervos cranianos de ratos inoculados com o vírus da raiva, porém vacinados contra a doença. Os achados no grupo não vacinado foram de degeneração axonal e intensa desmielinização dos nervos examinados. No grupo vacinado foram encontrados apenas discretas alterações da mielina, sem relevância do ponto de vista patológico. As grandes alterações ultraestruturais encontradas no grupo de ratos não vacinados sugerem que na raiva ocorram acentuadas alterações nos nervos cranianos e que tais alterações devem estar intimamente relacionadas ao quadro clínico da doença (hidrofobia). Além disso, é possível que tais alterações estejam associadas a um processo imunológico responsável também por acometimento sistêmico dos nervos periféricos.
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- 1997
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11. Identification of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel target of bisphenol A.
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Yuki Ito, Takumi Ito, Satoki Karasawa, Teruya Enomoto, Akihiro Nashimoto, Yasuyoshi Hase, Satoshi Sakamoto, Tsuneyo Mimori, Yoshihisa Matsumoto, Yuki Yamaguchi, and Hiroshi Handa
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Medicine ,Science - Abstract
Bisphenol A (BPA) forms the backbone of plastics and epoxy resins used to produce packaging for various foods and beverages. BPA is also an estrogenic disruptor, interacting with human estrogen receptors (ER) and other related nuclear receptors. Nevertheless, the effects of BPA on human health remain unclear. The present study identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a novel BPA-binding protein. DNA-PKcs, in association with the Ku heterodimer (Ku70/80), is a critical enzyme involved in the repair of DNA double-strand breaks. Low levels of DNA-PK activity are previously reported to be associated with an increased risk of certain types of cancer. Although the Kd for the interaction between BPA and a drug-binding mutant of DNA-PKcs was comparatively low (137 nM), high doses of BPA were required before cellular effects were observed (100-300 μM). The results of an in vitro kinase assay showed that BPA inhibited DNA-PK kinase activity in a concentration-dependent manner. In M059K cells, BPA inhibited the phosphorylation of DNA-PKcs at Ser2056 and H2AX at Ser139 in response to ionizing radiation (IR)-irradiation. BPA also disrupted DNA-PKcs binding to Ku70/80 and increased the radiosensitivity of M059K cells, but not M059J cells (which are DNA-PKcs-deficient). Taken together, these results provide new evidence of the effects of BPA on DNA repair in mammalian cells, which are mediated via inhibition of DNA-PK activity. This study may warrant the consideration of the possible carcinogenic effects of high doses of BPA, which are mediated through its action on DNA-PK.
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- 2012
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12. P-92 - Involvement of NMDA Receptors and Nitric Oxide in Ischemia-Induced Retinal Degeneration in Rats
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Adachi, K., Morizane, C., Yasuyoshi, H., Fujita, Y., Furutani, I., Hanno, Y., Kashii, S., Honda, Y., and Akaike, A.
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- 1997
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13. Inhibition of glutamate-induced nitric oxide synthase activation by dopamine in cultured rat retinal neurons.
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Yamauchi T, Kashii S, Yasuyoshi H, Zhang S, Honda Y, Ujihara H, and Akaike A
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- 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine pharmacology, Animals, Cells, Cultured, Dopamine metabolism, Dopamine Agonists pharmacology, Enzyme Activation, Kainic Acid pharmacology, N-Methylaspartate pharmacology, Nitric Oxide Synthase Type I, Patch-Clamp Techniques, Rats, Rats, Wistar, Receptors, Dopamine D1 physiology, Receptors, N-Methyl-D-Aspartate agonists, Retina cytology, Retina drug effects, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid pharmacology, Dopamine pharmacology, Excitatory Amino Acid Agonists pharmacology, Neurons enzymology, Nitric Oxide Synthase metabolism, Receptors, N-Methyl-D-Aspartate physiology, Retina enzymology
- Abstract
Previously, we showed that dopamine protects cultured retinal neurons from N-methyl-D-aspartate (NMDA) receptor mediated-glutamate excitotoxicity via dopamine D1 receptor. This study has demonstrated for the first time that nitric oxide synthase (NOS) plays a crucial role in dopamine-induced neuroprotection. Our patch clamp study has shown that dopamine does not affect the NMDA-induced whole cell current. Dopamine or SKF38393 (D1 receptor agonist) inhibited ionomycin (calcium ionophore)-induced toxicity, while dopamine did not affect S-nitrosocysteine (NO donor)-induced toxicity. Biochemical analysis on enzymatic activities has shown that dopamine or cAMP (which is generated through D1 receptor stimulation) inhibits glutamate induced-NOS activation. These results suggest that dopamine inhibits glutamate induced-NOS activation via D1 receptor, resulting in the protection of retinal neurons.
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- 2003
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14. Mitochondrial ATP-sensitive potassium channel: a novel site for neuroprotection.
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Yamauchi T, Kashii S, Yasuyoshi H, Zhang S, Honda Y, and Akaike A
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- Animals, Cell Culture Techniques, Cell Survival drug effects, Cytoprotection, Decanoic Acids pharmacology, Glyburide pharmacology, Hydroxy Acids pharmacology, Membrane Potentials physiology, Membrane Proteins antagonists & inhibitors, Mitochondria physiology, Molsidomine toxicity, Neurons cytology, Neurons metabolism, Nitroprusside toxicity, Potassium Channels, Rats, Rats, Wistar, Retina cytology, Retina metabolism, Bradykinin pharmacology, Diazoxide pharmacology, Glutamic Acid toxicity, Membrane Proteins metabolism, Molsidomine analogs & derivatives, Neurons drug effects, Neuroprotective Agents pharmacology, Retina drug effects
- Abstract
Purpose: It has been shown that bradykinin (BK) protects retinal neurons against glutamate excitotoxicity, but it was not clear how BK inhibits glutamate excitotoxicity. The purpose of this study was to investigate the effect of opening the mitochondrial adenosine triphosphate (ATP)-sensitive potassium (Mit K (ATP)) channel on glutamate excitotoxicity and the protective effect of BK using cultured retinal neurons., Methods: Primary cultures were obtained from the retina of fetal rats (gestation days 17-19). Glutamate neurotoxicity was assessed by 10-minute exposure to 1 mM glutamate followed by 1-hour incubation in glutamate-free medium, using the trypan blue exclusion method. BK, diazoxide (the opener of the Mit K (ATP) channel), 5HD, and glibenclamide (blockers of the Mit K (ATP) channel) were applied simultaneously with glutamate. Mitochondrial membrane potential was measured as the ratio of 590:527 nm fluorescence of JC-1., Results: Cell viability was markedly reduced by 10-minute exposure to 1 mM glutamate followed by 1-hour incubation in glutamate-free medium, and glutamate induced mitochondrial depolarization of retinal neurons. BK and diazoxide protected retinal neurons against glutamate excitotoxicity and inhibited glutamate-induced mitochondrial depolarization. These actions of BK and diazoxide were inhibited by the coapplication of 5HD and glibenclamide. Furthermore, diazoxide inhibited the sodium nitroprusside (SNP, NO donor) toxicity, but did not inhibit the 3-morpholinosydnonimine (SIN-1, NO, and superoxide donor) toxicity., Conclusions: These results suggest that BK and diazoxide protect retinal neurons against glutamate excitotoxicity by opening the Mit K (ATP) channel. It is suggested that opening of the Mit K (ATP) channel inhibited glutamate-induced generation of superoxide.
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- 2003
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15. New insight into the functional role of acetylcholine in developing embryonic rat retinal neurons.
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Yasuyoshi H, Kashii S, Kikuchi M, Zhang S, Honda Y, and Akaike A
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- Acetylcholine antagonists & inhibitors, Animals, Cells, Cultured, Cholinergic Agonists pharmacology, Cytoprotection drug effects, Dopamine Antagonists pharmacology, Dose-Response Relationship, Drug, Mecamylamine pharmacology, Muscarinic Antagonists pharmacology, Neurons drug effects, Neurons metabolism, Neuroprotective Agents antagonists & inhibitors, Nicotinic Antagonists pharmacology, Rats, Rats, Wistar, Receptors, N-Methyl-D-Aspartate metabolism, Retina drug effects, Retina metabolism, Time Factors, Acetylcholine pharmacology, Cell Survival drug effects, Glutamic Acid toxicity, Neurons cytology, Neuroprotective Agents pharmacology, Retina embryology
- Abstract
Purpose: To examine the effects of acetylcholine (ACh) on glutamate-induced neurotoxicity in embryonic rat retinal neurons., Methods: Primary cultures were obtained from rat retinas at embryonic days 17 to 19. Cultured cells were exposed to glutamate for 10 minutes, followed by incubation in glutamate-free medium for 1 hour. Drugs were added to the incubation medium for 1 to 24 hours until immediately before glutamate exposure and were removed from culture medium during glutamate exposure and the postincubation period. The neurotoxic effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method., Results: Cell viability was markedly reduced by 10-minute exposure to 500 microM glutamate followed by a 1-hour incubation in glutamate-free medium. Incubating the cultures with 1 microM ACh for 12 hours before glutamate exposure reduced glutamate neurotoxicity. A similar effect was induced by application of carbachol (1 microM). The protective effect of ACh against glutamate neurotoxicity was inhibited by a nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine (0.5 microM), whereas a muscarinic acetylcholine receptor (mAChR) antagonist, atropine (0.5 microM) did not affect ACh-induced protection. In addition, a similar protection was induced by application of nicotine (1 microM), but not by muscarine (1 microM). Pretreatment with nicotine induced a protective effect in a time-dependent manner, ranging from 1 to 12 hours. Pretreatment with nicotine at concentrations ranging from 0.001 to 1 microM induced dose-dependent protection against glutamate neurotoxicity. Furthermore, the protective action of nicotine was inhibited by simultaneous application of dopamine D1 receptor antagonist, SCH23390 (1 microM), with nicotine, whereas a dopamine D2 receptor antagonist, domperidone (1 microM), did not affect nicotine-induced protection., Conclusions: These results suggest that pretreatment of cultured rat retinal neurons with ACh or the nAChR agonists, nicotine and carbachol, has a protective action against glutamate neurotoxicity through nAChRs and that the dopamine release induced by nicotinic stimulation subsequently protects the retinal neurons by way of dopamine D1 receptors.
- Published
- 2002
16. Protective effects of ifenprodil against glutamate-induced neurotoxicity in cultured retinal neurons.
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Zhang S, Kashii S, Yasuyoshi H, Kikuchi M, Honda Y, Kaneda K, Sato S, and Akaike A
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- Animals, Cell Death, Cell Survival drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Fetus, Neurons cytology, Rats, Retina cytology, Spermidine pharmacology, Excitatory Amino Acid Antagonists pharmacology, Glutamic Acid toxicity, Neurons drug effects, Piperidines pharmacology, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Retina drug effects
- Abstract
Purpose: To examine the effects of ifenprodil on glutamate-induced neurotoxicity in cultured retinal neurons., Methods: Primary cultures obtained from the fetal rat retina (gestation day 17-19) were used for the experiment. Neurotoxicity effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method. The cells were exposed briefly (10 min) to excitatory amino acids (EAA, 1 mM) and then were incubated for 1 h in an EAA-free medium. Ifenprodil (10 mM) was added for the 10-min exposure to EAA and the subsequent 60-min incubation in an EAA-free medium., Results: Ifenprodil dose-dependently prevented cell death induced by glutamate or NMDA, but did not affect that induced by kainate. The protective effects of ifenprodil against glutamate neurotoxicity were significantly reduced by spermidine, a polyamine modulatory site agonist, but not by glycine, a strychnine-insensitive glycine site agonist., Conclusion: The findings suggest that ifenprodil protected the cultured retinal cells we used in this study against glutamate neurotoxicity by its inhibitory action on the polyamine modulatory site of the NMDA receptor.
- Published
- 2000
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17. Protective effect of bradykinin against glutamate neurotoxicity in cultured rat retinal neurons.
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Yasuyoshi H, Kashii S, Zhang S, Nishida A, Yamauchi T, Honda Y, Asano Y, Sato S, and Akaike A
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- Adrenergic beta-Antagonists pharmacology, Animals, Bradykinin Receptor Antagonists, Cell Survival, Cells, Cultured, Dose-Response Relationship, Drug, Electrophoresis, Agar Gel, Ionomycin toxicity, Molsidomine toxicity, Neurons cytology, Neurons metabolism, Nitroprusside toxicity, RNA, Messenger biosynthesis, Rats, Rats, Wistar, Receptor, Bradykinin B2, Receptors, Bradykinin biosynthesis, Receptors, Bradykinin genetics, Retina cytology, Retina metabolism, Reverse Transcriptase Polymerase Chain Reaction, Bradykinin analogs & derivatives, Bradykinin pharmacology, Glutamic Acid toxicity, Molsidomine analogs & derivatives, Neurons drug effects, Neuroprotective Agents pharmacology, Retina drug effects
- Abstract
Purpose: To identify the localization and expression of bradykinin (BK)-B2 receptors in rat retina and examine the effects of BK on glutamate-induced neurotoxicity using cultured rat retinal neurons., Methods: An immunohistochemical study using a specific antibody against BK-B2 receptor was performed with rat retina. Primary cultures were obtained from the retina of fetal rats (gestation day 17-19). Expression of BK-B2 receptor mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR) using total RNA obtained from cultured retinal neurons. Cultured cells were exposed to glutamate (1 mM) for 10 minutes and followed by incubation in glutamate-free medium for 1 hour. The effects of BK were assessed by simultaneous application of BK with glutamate. The neurotoxic effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method., Results: Immunohistochemical study demonstrated that BK-B2 receptors were expressed in the ganglion cell, inner nuclear layers, and outer nuclear layers. Furthermore, BK-B2 receptor mRNA expression was observed in cultured retinal neurons. Cell viability was markedly reduced by 10-minute exposure to 1 mM glutamate followed by a 1-hour incubation in glutamate-free medium. Simultaneous application of BK at concentrations of 0.001 to 1 microM with glutamate demonstrated dose-dependent protection against glutamate neurotoxicity. The protective action of BK (1 microM) was inhibited by simultaneous application of BK-B2 receptor antagonist, Hoe140 (1 microM). Furthermore, 1 microM BK had protective effects on neurotoxicity induced by 1 microM ionomycin, a calcium ionophore, and sodium nitroprusside (SNP, 500 microM), a nitric oxide (NO)-generating agent. However, BK did not inhibit neurotoxicity induced by 3-morpholinosydnonimine (SIN-1, 10 microM), an NO and oxygen radical donor., Conclusions: These results suggest that BK-B2 receptors were distributed in rat retinas and cultured retinal neurons and that BK had a protective action against glutamate neurotoxicity through BK-B2 receptors in cultured retinal neurons. It is suggested that BK-induced protection against glutamate neurotoxicity took place downstream to NO generation and upstream to oxygen radical generation.
- Published
- 2000
18. Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina.
- Author
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Toriu N, Akaike A, Yasuyoshi H, Zhang S, Kashii S, Honda Y, Shimazawa M, and Hara H
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- Animals, Cells, Cultured, Dizocilpine Maleate therapeutic use, Dose-Response Relationship, Drug, Flunarizine therapeutic use, Male, Neuroprotective Agents therapeutic use, Neurotoxicity Syndromes etiology, Rats, Rats, Sprague-Dawley, Calcium Channel Blockers therapeutic use, Glutamic Acid adverse effects, Neurotoxicity Syndromes drug therapy, Piperazines therapeutic use, Reperfusion Injury prevention & control
- Abstract
We examined the effects of a new Ca2+ channel blocker, lomerizine, on the intraocular hypertension-induced ischemia/reperfusion injury in rat retina and on the glutamate-induced neurotoxicity in rat cultured retinal neurons, and compared its effects with those of a Ca2+ channel blocker (flunarizine) and an N-methyl-D-aspartate receptor antagonist (MK-801). Morphometric evaluation at 7 days after ischemia/reperfusion showed that treatment with lomerizine (0.1 and 1 mg kg(-1), i.v.) prior to ischemia and again immediately after reperfusion dose-dependently reduced the retinal damage. Treatment with MK-801 (1 mg kg(-1), i.v.) before ischemia significantly reduced the resulting retinal damage. Flunarizine (0.1 and 1 mg kg(-1), i.v.) tended to reduce the retinal damage, but its effect did not reach statistical significance. In an in vitro study, pretreatment with lomerizine (0.1 and 1 microM) or flunarizine (1 microM) significantly reduced glutamate-induced neurotoxicity, the effects being concentration dependent. Lomerizine (1 microM) also exhibited protective effects against both the N-methyl-D-aspartate and kainate induced types of neurotoxicity. However, lomerizine (1 microM) had little effect on the neurotoxicity induced by ionomycin (1 microM) application. Glutamate-induced neurotoxicity was abolished by removing Ca2+ from the medium. These results indicate that lomerizine protects neuronal cells against retinal neurotoxicity both in vivo and in vitro, and that this Ca2+ channel blocker may be useful as a therapeutic drug against retinal diseases that cause neuronal injury, such as normal tension glaucoma (NTG).
- Published
- 2000
- Full Text
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19. Protective effects of FK506 against glutamate-induced neurotoxicity in retinal cell culture.
- Author
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Kikuchi M, Kashii S, Mandai M, Yasuyoshi H, Honda Y, Kaneda K, and Akaike A
- Subjects
- Animals, Calcineurin Inhibitors, Calcium metabolism, Cell Culture Techniques, Cell Survival drug effects, Cyclosporine pharmacology, Dose-Response Relationship, Drug, Fetus, Neurons enzymology, Nitric Oxide metabolism, Nitric Oxide Synthase metabolism, Polyenes pharmacology, Rats, Retina enzymology, Sirolimus, Tacrolimus antagonists & inhibitors, Glutamic Acid toxicity, Neurons drug effects, Retina drug effects, Tacrolimus pharmacology
- Abstract
Purpose: To examine the effects of FK506 on glutamate neurotoxicity in cultured retinal neurons., Methods: Experiments were performed with primary retinal cultures obtained from 17- to 19-day-old rat fetuses. To assess the effects of FK506 and other drugs on glutamate neurotoxicity, cultures were treated with a drug beginning 10 minutes before application of glutamate and continuing during the subsequent 10 minutes of glutamate exposure. The treated cells were then incubated for 1 hour in a drug-free and glutamate-free medium. After a 1-hour incubation, cell viability was quantitatively measured by the trypan blue exclusion method., Results: Brief exposure to glutamate markedly decreased cell viability. FK506 protected against glutamate neurotoxicity in a dose-dependent manner. Rapamycin is a competitive inhibitor of FK506 that binds FK506 binding protein. Simultaneous application of rapamycin and FK506 negated the protective effects of FK506. Cyclosporin A, which binds and inhibits calcineurin, mimicked the protective effects of FK506. Treatment with FK506 did not affect the intracellular maximum Ca2+ concentration induced by glutamate application. Although FK506 exhibited protective action against Ca2+ ionophore-induced neurotoxicity, it had no effect on nitric oxide-induced neurotoxicity. Treatment with FK506 reduced the activity of nitric oxide synthase (NOS)., Conclusion: FK506 protected against glutamate neurotoxicity by inhibiting NOS activity in cultured retinal neurons.
- Published
- 1998
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