Protection against hypoxia-induced increase in blood-brain barrier permeability:: role of tight junction proteins and NF-κB
Protection against hypoxia-induced increase in blood-brain barrier permeability:: role of tight junction proteins and NF-κB
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DOI：
10.1242/jcs.00264
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发表时间：
2003-02-15
影响因子：
4
通讯作者：
Davis, TP
中科院分区：
文献类型：
--
作者：
Brown, RC;Mark, KS;Davis, TP
与神经胶质细胞和神经胶质条件培养基共培养可以诱导微血管内皮细胞的血脑屏障特性，并防止缺氧引起的血脑屏障破坏。我们检查了两种类型的神经胶质条件培养基对脑微血管内皮细胞通透性和紧密连接蛋白表达的影响，并研究了潜在的作用机制。我们发现，C6 神经胶质瘤条件培养基（而非大鼠星形胶质细胞条件培养基）可以防止因暴露于 1% 氧气 24 小时而引起的通透性增加。这种缺氧应激导致紧密连接蛋白claudin-1和肌动蛋白的表达增加，特别是在用C6条件培养基处理的细胞中。我们发现 C6 条件培养基的碱性成纤维细胞生长因子和血管内皮生长因子水平显着较高。用 C6 条件培养基处理 1 或 3 天可防止缺氧引起的通透性增加，这种保护作用可能是通过终止于转录因子 NFkappaB 的信号转导途径介导的。
Co-culture with glial cells and glia-conditioned media can induce blood-brain barrier properties in microvessel endothelial cells and protect against hypoxia-induced blood-brain barrier breakdown. We examined the effect of two types of glia-conditioned media on brain microvessel endothelial cell permeability and tight junction protein expression, and studied potential mechanisms of action. We found that C6-glioma-conditioned media, but not rat astrocyte-conditioned media, protected against an increase in permeability induced by exposure to 1% oxygen for 24 hours. This hypoxic stress caused an increase in the expression of tight junction proteins claudin-1 and actin, particularly in cells treated with C6-conditioned media. We found that C6-conditioned media has a significantly higher level of both basic fibroblast growth factor and vascular endothelial growth factor. Treatment with C6-conditioned media for 1 or 3 days protects against hypoxia-induced permeability increases, and this protective effect may be mediated by signal transduction pathways terminating at the transcription factor NFkappaB.