The Nitric Oxide Donor NOC12 Protects Cultured Astrocytes Against Apoptosis via a cGMP-Dependent Mechanism.

• Takuma Kazuhiro

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University

• Phuagphong Patamawan

  Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University

• Lee Eibai

  Department of Pharmacology, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University

• Enomoto Riyo

  Department of Pharmacology, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University

• Mori Koichi

  Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences and High Technology Research Center, Kobe Gakuin University

• Baba Akemichi

  Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University

• Matsuda Toshio

  Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University

抄録

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.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 89 (1), 64-71, 2002

  公益社団法人 日本薬理学会

キーワード

• Nitric oxide
• NOC12
• Apoptosis
• cGMP
• Astrocyte

詳細情報

• CRID: 1390282679262706048
• NII論文ID: 10008431063
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.89.64
• COI: 1:STN:280:DC%2BD38zktFSmuw%3D%3D
• ISSN: 13473506
• ISSN: 00215198
• NDL書誌ID: 6170938
• PubMed: 12083744
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I6170938
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819301489?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0021519819301489?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2002273765
• 本文言語コード: en
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