HIF2来自于星胶,对EPO作用.pptVIP

The Transcriptional Activator Hypoxia Inducible Factor 2 (HIF-2/EPAS-1) Regulates the Oxygen-Dependent Expression of Erythropoietin in Cortical Astrocytes The Journal of Neuroscience, September 13, 2006 ? 许明月 2013.7.4 组织缺氧 HIF-1 缺氧诱导因子 HIFβ HIFα LDH、VEGF、EPO EPO 促进神经干细胞再生、存活，调节血管再生等 Background HIFα HIF1α HIF2α HIF3α 表达最广泛 肝脏，肿瘤细胞，成神经细胞瘤 组织特异性 EPO Methods Neuronal. Astrocyte cultures Differential expression of EPO、HIF1 α、 HIF2 α OGD Connection? siRNA Cre-loxP Confirm? IN VIVO in the hypoxic brain Results 1、Differential expression of EPO and VEGF in neurons and astrocytes 不同细胞分泌量 2、Expression of HIF-1 α, HIF-2 α, and ARNT2 in cultured neurons and astrocytes A B HIF- β Supershift. free probe nonspecific binding Constitutive binding activity 3、Cre recombinase-mediated deletion of HIF-1 α does not affect hypoxia-induced EPO expression in cortical astrocytes 24 h, 0.5% O2 RT-PCR EPO LDH VEGF 4、HIF-2 α knockdown by RNA interference prevents hypoxia-induced EPO expression in cortical astrocytes 5、HIF-2 α binds to the EPO promoter in cultured astrocytes 6、Constitutive activation of HIF-2 α is sufficient to induce EPO expression 过表达： mtHIF-1 α、mtHIF-2 α： 含脯氨酸残基，伴随氧气浓度降低，表达量不断上升 HIF-1–VP16 fusion protein： 缺乏脯氨酸残基 7、HIF-2 α -dependent factors secreted by astrocytes affect the survival of neurons exposed to oxygen-glucose deprivation normoxic Hypoxic 8%，24h EPO-positive astrocytes and capillaries (red). HIF-2-positive nuclei (green 8、HIF-2 α mediates the prosurvival signaling of astrocytes to neurons. Ab：antibody against EPO Hypoxia normoxic Thanks * *