TAILIEUCHUNG - Báo cáo khoa học: Hypoxia-driven proliferation of embryonic neural stem ⁄ progenitor cells – role of hypoxia-inducible transcription factor-1a

We recently reported that intermittent hypoxia facilitated the proliferation of neural stem⁄progenitor cells (NPCs) in the subventricule zone and hip-pocampusin vivo. Here, we demonstrate that hypoxia promoted the prolif-eration of NPCsin vitro and that hypoxia-inducible factor (HIF)-1a, which is one of the key molecules in the response to hypoxia, was critical in this process. | ễFEBS Journal Hypoxia-driven proliferation of embryonic neural stem progenitor cells - role of hypoxia-inducible transcription factor-1 a Tong Zhao1 z Cui-ping Zhang1 z Zhao-hui Liu1 Li-ying Wu1 Xin Huang1 Hai-tong Wu1 Lei Xiong1 Xuan Wang2 Xiao-min Wang2 Ling-ling Zhu1 and Ming Fan1 2 1 Department of Brain Protection and Plasticity Institute of Basic MedicalSciences Beijing China 2 Key Laboratory for Neurodegenerative Disorders of the Ministry of Education and Department of Physiology CapitalMedicalUniversity Beijing China Keywords embryonic neural stem or progenitor cells HIF-1a hypoxia proliferation Correspondence L. -l. Zhu Department of Brain Protection and Plasticity Institute of Basic Medical Sciences Beijing China No. 27 Taiping Rd Beijing 100850 China Fax 86 10 6821 3039 Tel 86 6821 0077 ext. 931315 E-mail linglingzhu@ M. Fan Department of Brain Protection and Plasticity Institute of Basic Medical Sciences Beijing China Taiping Rd Beijing 100850 China Fax 86 10 6821 3039 Tel 86 10 6821 4026 E-mail fanming@ These authors contributed equally to this work Received 20 November 2007 revised 3 February 2008 accepted 15 February 2008 doi We recently reported that intermittent hypoxia facilitated the proliferation of neural stem progenitor cells NPCs in the subventricule zone and hippocampus in vivo. Here we demonstrate that hypoxia promoted the proliferation of NPCs in vitro and that hypoxia-inducible factor HIF -1a which is one of the key molecules in the response to hypoxia was critical in this process. NPCs were isolated from the rat embryonic mesencephalon and exposed to different oxygen concentrations 20 O2 10 O2 and 3 O2 for 3 days. The results showed that hypoxia especially 10 O2 promoted the proliferation of NPCs as assayed by bromodeoxyuridine incorporation neurosphere formation and proliferation index. The level of HIF-1a mRNA and protein expression detected by RT-PCR and western blot

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