The Nitric Oxide Donor NOC12 Protects Cultured Astrocytes Against Apoptosis via a cGMP-Depentent Mechanism
スポンサーリンク
概要
- 論文の詳細を見る
We examined the effect of 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC12), a nitric oxide (NO) donor, on apoptosis in cultured astrocytes. Reperfusion after hydrogen peroxide (H2O2) exposure caused a decrease in cell viability, loss of mitochondrial membrane potential, caspase-3 activation, DNA ladder formation, and nuclear condensation. NOC12 at 10 – 100 μM significantly attenuated these apoptotic changes, while the NO donor at 1 mM caused cell injury and exacerbated the H2O2-induced cell injury. NOC12 increased intracellular cGMP levels in a dose dependent manner with the maximal effect at 100 μM. The protective effect of NOC12 was mimicked by the NO-independent guanylate cyclase activator 3-(5-hydroxymethyl-2-furyl)-1-benzyl indazole, and was attenuated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cGMP-dependent protein kinase inhibitor KT5823. ODQ and KT5823 did not block but rather exacerbated the cytotoxic effect of NOC12 at 1 mM. These findings demonstrate that lower concentrations of NOC12 inhibit the H2O2-induced apoptosis of astrocytes in a cGMP-dependent way, but higher concentrations of NOC12 show a toxic effect on astrocytes in a cGMP-independent way.
- 社団法人 日本薬理学会の論文
- 2002-05-01
著者
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MORI Koichi
Department of Aerospace Engineering, Nagoya University
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BABA Akemichi
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka Univers
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Baba A
Laboratory Of Molecular Neuropharmacology Graduate School Of Pharmaceutical Sciences Osaka Universit
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Baba Akemichi
Lab. Of Veterinary Pharmacology Graduate School Of Life And Environmental Sci. Osaka Prefecture Univ
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Baba A
Laboratory Of Molecular Neuropharmacology
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Baba Akemichi
Laboratory Of Molecular Neuropharmacology Graduate School Of Pharmaceutical Sciences Osaka Universit
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Baba Akemichi
昭和大学藤が丘病院 循環器内科
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Baba A
昭和大学藤が丘病院 循環器内科
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Baba A
Osaka Univ. Osaka Jpn
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Baba Akemichi
サントリー生物医学研究所
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Matsuda T
Lab. Of Medicinal Pharmacology Graduate School Of Pharmaceutical Sciences Osaka Univ.
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MATSUDA Toshio
Graduate School of Pharmaceutical Sciences, Osaka University
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TAKUMA Kazuhiro
Department of Analytical Chemistry
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PHUAGPHONG Patamawan
Laboratory of Molecular Neuropharmacology
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LEE Eibai
Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
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ENOMOTO Riyo
Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University
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Takuma K
Laboratory Of Molecular Neuropharmacology Graduate School Of Pharmaceutical Sciences Osaka Universit
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Matsuda Toshio
Graduate School Of Pharmaceutical Sciences Osaka University
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Baba Akemichi
Laboratory Of Molecular Neuropharmacology
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Lee E
Faculty Of Pharmaceutical Sciences And High Technology Research Center Kobe Gakuin University
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Enomoto Riyo
Faculty Of Pharmaceutical Sciences And High Technology Research Center Kobe Gakuin University
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Phuagphong Patamawan
Laboratory Of Molecular Neuropharmacology Graduate School Of Pharmaceutical Sciences Osaka Universit
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Mori Koichi
Department Of Analytical Chemistry
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