Mechanisms of [2,3-Butanedione Bis(N^4-Dimethylthiosemicarbazone)] zinc(Zn-ATSM_2)-Induced Protection of Cultured Hippocampal Neurons Against N-Methyl-_D-Aspartate Receptor-Mediated Glutamate Cytotoxicity
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概要
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Hyperexcitation of glutamatergic neurons may play a key role in ischemia-related neurodegeneration. Recent studies have suggested that the zinc ion (Zn2+), which is present in the central nervous system, has a modulatory role in glutamatergic neuron activity. Zinc ions block glutamate-induced depolarizing currents and neuronal damage by binding with zinc sites on the NMDA subtypes. Therefore, we examined the usefulness of zinc as a therapeutic agent for the prevention of ischemic neuronal damage in the brain. In our previous study, 2, 3-butanedione bis(N4-dimethylthiosemicarbazonato) zinc complex (Zn-ATSM2), with high brain uptake, showed significant neuroprotective effects against cerebral ischemia in rats when administered systemically. In this study, to elucidate the mechanism of the neuroprotective effect of Zn-ATSM2, we first examined its in vitro protective effects against glutamate-, NMDA- and kainite-induced neurotoxicity in primary cultures of hippocampal neurons. Zn-ATSM2 elicited protective effects against this glutamate- and NMDA-induced neurotoxicity, but did not affect kainite-induced cytotoxicity. In addition, we studied the effects of Zn-ATSM2 on influx of Ca2+, which undergoes modification subsequent to NMDA activation. Zn-ATSM2 significantly decreased glutamate-induced 45Ca2+ uptake. Thus, Zn-ATSM2 protected against glutamate-induced neurotoxicity and its protective effect was, at least in part, due to the blockage of NMDA receptor-mediated Ca2+ influx.
- 社団法人 日本薬理学会の論文
- 2000-11-01
著者
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Saji Hideo
明治鍼灸大学
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Saji Hideo
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Saji Hideo
茨城県立医療大学 放射線技術科学
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Magata Y
Photon Medical Research Center Hamamatsu University School Of Medicine:molecular Imaging Frontier Re
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Magata Yasuhiro
京都大学 医学研究科心臓血管外科学
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Magata Yasuhiro
浜松医科大学附属光量子医学研究センター
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Saji Hideo
Graduate School Of Pharmaceutical Sciences Kyoto University
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IIDA Yasuhiko
Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine
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Magata Y
Laboratory Of Genome-bio Photonics Photon Medical Research Center Hamamatsu University School Of Med
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Yasuhiro Magata
Photon Medical Research Center Hamamatsu University School Of Medicine:molecular Imaging Frontier Re
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Kitamura Youji
Department Of Pharmaceutical Sciences Graduate School Of Medicine And Dentistry And Pharmaceutical S
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MAGATA Yasuhiro
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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KUBOTA Megumi
Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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KAWASHIMA Hideaki
Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Ida Yuko
Department Of Applied Pharmacology Graduate School Of Medicine And Pharmaceutical Sciences Universit
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Ishii Yasushi
Third Division Dept. Of Internal Medicine And Nuclear Medicine
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Kubota Megumi
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kubota Megumi
Department Of Nutritional Science Faculty Of Health And Welfare Science Okayama Prefectural Universi
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Iida Y
Department Of Bioimaging Medical Sciences Gunma University
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Iida Yasuhiko
Department Of Bioimaging Medical Sciences Gunma University
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Iida Yasuhiko
Department Of Radiopharmaceutical Chemistry Faculty Of Pharmaceutical Sciences Kyoto University
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Magata Yasuhiro
Department Of Nuclear Medicine Graduate School Of Medicine
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Sakahara H
Department Of Radiology Hamamatsu University School Of Medicine
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KAWASHIMA Hidekazu
Kyoto University Hospital
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Miyake Yoshinori
Department Of Radiology And Nuclear Medicine National Cardiovascular Center
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Kawashima Hideaki
Kyoto University Hospital
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Yamamuro Masaki
Department Of Diagnostic Imaging And Nuclear Medicine Kyoto University Graduate School Of Medicine
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Saji Hideo
Dep. Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Univ.
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Kuge Yuji
Department Of Tracer Kinetics Hokkaido University School Of Medicine
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Kuge Yuji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kitamura Youji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Sakahara H
Kyoto Univ. School Of Medicine
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Kawashima Hideaki
Graduate School Of Pharmaceutical Sciences Kyoto University
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Saji Hideo
Department Of Cardiology Matsushita Memorial Hosipital
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Kitamura Youji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kawashima H
Kyoto Univ.
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