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

• Published in: European journal of pharmacology 2007-11, Vol.573 (1), p.20-28
• Main Authors: Ohashi, Hiroki, Nishikawa, Kaori, Ayukawa, Koichi, Hara, Yoko, Nishimoto, Mika, Kudo, Yoshihisa, Abe, Toshiaki, Aoki, Shunsuke, Wada, Keiji
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Agonists; Adrenergic alpha-Agonists - pharmacology; Animals; Biological and medical sciences; Caspase 3 - metabolism; Caspase 7 - metabolism; Caspase Inhibitors; Cell death; Cell Death - drug effects; Cell Death - physiology; Cell Differentiation - drug effects; Cell stress; Cells, Cultured; Cirazoline; Culture Media - chemistry; Culture Media - pharmacology; Female; Gene Expression - drug effects; GPCR; Imidazoles - pharmacology; Immunohistochemistry; L-Lactate Dehydrogenase - antagonists & inhibitors; L-Lactate Dehydrogenase - drug effects; L-Lactate Dehydrogenase - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Neural progenitor cell; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Pharmacology. Drug treatments; Phenylephrine; Phenylephrine - pharmacology; Pregnancy; Receptors, Adrenergic, alpha-1 - genetics; Receptors, Adrenergic, alpha-1 - physiology; Reverse Transcriptase Polymerase Chain Reaction; Staurosporine - pharmacology; Stem Cells - cytology; Stem Cells - drug effects; Stem Cells - metabolism; Stress, Mechanical; Telencephalon - cytology; Telencephalon - drug effects; Telencephalon - metabolism; Tunicamycin - pharmacology; α 1-adrenoceptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.06.060

Here, we show that α 1-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 α 1-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 α 1-adrenoceptor agonists inhibit caspase-3/7-independent death of the embryonic NPCs.