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p38 and JNK MAPK, but not ERK1/2 MAPK, play important role in colchicine-induced cortical neurons apoptosis.
Yang, Yi; Zhu, Xiaonan; Chen, Yuanbin; Wang, Xuelan; Chen, Ruzhu.
Afiliação
  • Yang Y; Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
Eur J Pharmacol ; 576(1-3): 26-33, 2007 Dec 08.
Article em En | MEDLINE | ID: mdl-17716651
ABSTRACT
Colchicine is a microtubule interfering agent and is able to induce neural apoptosis. However, the intracellular pathway involved in its neurotoxicity is still unclear. In the present study, three of mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase 1/2 (ERK1/2) were investigated in colchicine-induced apoptosis on cortical neurons for the first time. Our results showed that 1 microM colchicine administration in primarily cultured cortical neurons led to typical neuronal apoptosis, and the apoptosis was attenuated by taxol, a microtubule stabilizer. Moreover, activation of p38 MAPK was found for the first time, as well as that of JNK MAPK, but not of ERK1/2 MAPK, after colchicine exposure. Apoptosis was inhibited by p38 MAPK inhibitors, SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole), SB239063 (trans-1-(4-hydroxycyclohexyl)-4-(fluorophenyl)-5-(2-methoxypyrimidin-4-yl) imidazole), and JNK MAPK pathway inhibitors, CEP11004 (9,12-epoxy-1H-diindolo[1,2,3-fg3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid, 2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-5,16-bis[[(1-methylethyl)thio]methyl]-1-oxo-, methyl ester, (9S,10R,12R)-), SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one). However, PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) and U0126 (1,4-diamino-2,3-dicyano-1, 4-bis[2-aminophenylthio]butadiene), ERK1/2 MAPK inhibitors, did not work. Furthermore, better neuronal protective effects were achieved by using JNK and the p38 MAPK inhibitors together as compared to that by using either alone. The results suggested that p38 MAPK, JNK MAPK, but not ERK1/2 MAPK may play pivotal role in colchicine's neurotoxicity in primarily cultured cortical neurons, and the protective effects of the inhibition of p38 or JNK MPAK on cortical neurons were synergistically.
Assuntos
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Base de dados: MEDLINE Assunto principal: Colchicina / Proteínas Quinases Ativadas por Mitógeno / Neurônios Idioma: En Ano de publicação: 2007 Tipo de documento: Article País de afiliação: China
Buscar no Google
Base de dados: MEDLINE Assunto principal: Colchicina / Proteínas Quinases Ativadas por Mitógeno / Neurônios Idioma: En Ano de publicação: 2007 Tipo de documento: Article País de afiliação: China