HIF-1alpha induced-VEGF在骨髓干细胞过度保护对缺血心肌细胞。

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王戴Y,徐M, Y,帕夏Z,李T,阿什拉夫米

HIF-1alpha induced-VEGF在骨髓干细胞过度保护对缺血心肌细胞。

J摩尔细胞心功能杂志。2007年6月,42 (6):1036 - 44。Epub 2007年4月6日。

PubMed ID

17498737 (在PubMed

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文摘

缺氧诱导factor-1alpha (HIF-1alpha)是一个proangiogenic转录因子稳定并激活在缺氧。它调节众多目标基因的表达,包括血管内皮生长因子(VEGF)和其他cytoprotective蛋白质。在这项研究中,我们假设骨髓干细胞(bmsc)分泌生长因子通过HIF-1alpha通路保护心肌细胞。bmsc来源于转基因老鼠overexpressing绿色荧光蛋白(GFP)。这项研究进行了体外使用bmsc与心肌细胞的共培养。肝癌和LDH释放,吸收、DNA碎片和annexin-V阳性细胞作为细胞损伤标记。HIF-1alpha蛋白质水平以及其活性形式和VEGF通过ELISA测定。HIF-1alpha和VEGF的表达分析了综合定量PCR和细胞定位是由免疫组织化学。LDH释放增加,MTT吸收减少心肌细胞缺氧30 h曝光后,预防的bmsc培养心肌细胞。心肌细胞缺氧诱导细胞凋亡和H (2) O(2)也减少了与企业综合培养。 VEGF release from BMSCs was significantly increased in parallel with high level of HIF-1alpha in BMSCs following anoxia or hypoxia in a time-dependent manner. Although no significant up-regulation could be seen in HIF-1alpha mRNA, HIF-1alpha protein and its activated form were markedly increased and translocated to the nucleus or peri-nuclear area. The increase and translocation of HIF-1alpha in BMSCs were completely blocked by 2-methoxyestradiol (2-ME2; 5 mumol), a HIF-1alpha inhibitor. Moreover, the protection of cardiomyocytes by BMSC and VEGF secretion was abolished by neutralizing HIF-1alpha antibody in a concentration dependent manner (200-3200 ng/ml). Bone marrow stem cells protect cardiomyocytes by up-regulation of VEGF via activating HIF-1alpha.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
2-Methoxyestradiol	低氧诱导因子1α	蛋白质	人类	未知的	不可用	细节