Alpha 1-adrenoceptor agonists protect against stress-induced death of neural progenitor cells.
Here, we show that alpha(1)-adrenoceptor agonists suppress stress-induced death of mouse embryonic brain-derived neural progenitor cells (NPCs). NPCs highly expressed both alpha(1A)- and alpha(1B)-adrenoceptor genes, whereas the gene encoding alpha(1D)-adrenoceptor was expressed at low levels. Application of the alpha(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 approximately 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 alpha(1)-adrenoceptor agonists inhibit caspase-3/7-independent death of the embryonic NPCs.
Ohashi
Hiroki
H
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
Nishikawa
Kaori
K
Ayukawa
Koichi
K
Hara
Yoko
Y
Nishimoto
Mika
M
Kudo
Yoshihisa
Y
Abe
Toshiaki
T
Aoki
Shunsuke
S
Wada
Keiji
K
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011247:Pregnancy; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013314:Stress, Mechanical; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D061945:Caspase Inhibitors; D003470:Culture Media; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D014415:Tunicamycin; D010656:Phenylephrine; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053179:Caspase 7; D019311:Staurosporine; C014282:cirazoline