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Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

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Neuro2a 細胞における神経突起伸長および過酸化水素誘 発細胞毒性に対するカルバゾール誘導体の影響

古川美子 *、澤本篤志 *、山岡美月 *、中屋真希子 *、稗田雄三、町支臣成、

波多江典之 **、奥山 聡 *、中島光業 *、日比野俐

Molecules, 24, 1366-1376 (2019)

Effects of Carbazole Derivatives on Neurite Outgrowth and Hydrogen Peroxide-Induced Cytotoxicity in Neuro2a Cells

Yoshiko Furukawa, Atsushi Sawamoto, Mizuki Yamaoka, Makiko Nakaya, Yuhzo Hieda, Tominari Choshi, Noriyuki Hatae, Satoshi Okuyama,

Mitsunari Nakajima, Satoshi Hibino

ABSTRACT: Many studies have demonstrated that oxidative stress plays an important role in several ailments including neurodegenerative diseases and cerebral ischemic injury.

Previously we synthesized some carbazole compounds that have anti-oxidant ability in vitro. In this present study, we found that one of these 22 carbazole compounds, compound 13 (3-ethoxy-1-hydroxy-8-methoxy-2-methylcarbazole-5-carbaldehyde), had the ability to protect neuro2a cells from hydrogen peroxide-induced cell death. It is well known that neurite loss is one of the cardinal features of neuronal injury. Our present study revealed that compound 13 had the ability to induce neurite outgrowth through the PI3K/Akt signaling pathway in neuro2a cells. These findings suggest that compound 13 might exert a neurotrophic effect and thus be a useful therapy for the treatment of brain injury

抄録 抗酸化作用をもつカルバゾール誘導体の 1 つである化合物13(3-ethoxy-1- hydroxy-8-methoxy-2-methylcarbazole-5-carbaldehyde)が、neuro2a 細胞を過酸化水素か ら保護する能力をもっていることを発見し、neuro2a 細胞の PI3K/Akt シグナル伝達経路 を介して神経突起伸長を誘導する能力を持っていることも明らかにしている。 これらの ことより、化合物13が神経栄養効果を発揮し、脳損傷の治療のための有用な治療法にな る可能性があることを示唆している内容である。

* 松山大学薬学部

  Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences,   Matsuyama University

** 横浜薬科大学薬学部

  Faculty of Pharmaceutical Sciences, Yokohama University of Pharmacy

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