Alpha 1-adrenoceptor agonists protect against stress-induced death of neural progenitor cells

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• 作者：Hiroki Ohashi ; Kaori Nishikawa ; Koichi Ayukawa ; Yoko Hara ; Mika Nishimoto ; Yoshihisa Kudo ; Toshiaki Abe ; Shunsuke Aoki ; Keiji Wada
• 关键词：α ; ₁-adrenoceptor ; GPCR ; Neural progenitor cell ; Cell death ; Cell stress ; Phenylephrine ; Cirazoline
• 刊名：European Journal of Pharmacology
• 出版年：2007
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：14 November 2007
• 卷：573
• 期：1-3
• 页码：20-28
• 文件大小：845 K

摘要

Here, we show that α₁-adrenoceptor agonists suppress stress-induced death of mouse embryonic brain-derived neural progenitor cells (NPCs). NPCs highly expressed both α_1A- and α_1B-adrenoceptor genes, whereas the gene encoding α_1D-adrenoceptor was expressed at low levels. Application of the α₁-adrenoceptor agonists phenylephrine and cirazoline significantly promoted cell survival of embryonic NPCs that had been exposed to stress, as measured by a lactate dehydrogenase release assay, but had no remarkable effect on differentiation of the NPCs. Both phenylephrine and cirazoline protected NPCs from death induced by growth factor deprivation, N2 nutrient deprivation, tunicamycin treatment or staurosporine treatment. Phenylephrine and cirazoline treatments both maximally reduced stress-induced cell death by 60%but did not change the percentage of undifferentiated cells as measured by nestin staining. Moreover, phenylephrine and cirazoline treatments did not affect the cellular activities of caspase-3 and caspase-7 but markedly reduced propidium iodide penetration into the cytoplasm, suggesting that α₁-adrenoceptor agonists inhibit caspase-3/7-independent death of the embryonic NPCs.