Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells
Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells
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DOI：
10.1002/jcb.21261
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发表时间：
2007-08-15
影响因子：
4
通讯作者：
Grimm, Daniela
中科院分区：
文献类型：
--
作者：
Infanger, Manfred;Ulbrich, Claudia;Grimm, Daniela
许多太空任务表明，长时间的太空飞行可能会增加心血管疾病的风险。使用三维回转器，我们研究了人类内皮EA.hy926细胞长达10天的条件下模拟微重力（微克），以区分从长期的影响微克和1克的瞬时。所有选择的基因的最大表达发生在10分钟后的旋转。基因表达（骨桥蛋白，Fas，TGF-β（1））下降到轻微上调水平或再次上升（半胱天冬酶-3）后，第四天的旋转。Caspase-3、Bax和Bcl-2蛋白含量在微重力条件下持续10天增加。此外，可检测到I型和III型胶原蛋白的长期积累以及细胞骨架α和β微管蛋白和F-肌动蛋白的改变。在模拟微重力条件下，脑源性神经营养因子、组织因子、血管内皮生长因子和内皮素-1的可溶性因子释放量显著减少，内皮素-1对保持心血管平衡很重要。内皮素-1的基因表达在μ g条件下在第7天和第10天被抑制。血管内皮的改变加上内皮素-1释放的减少可能会对宇航员造成飞行后的健康危害。
Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (mu g) to distinguish transient from long-term effects of mu g and 1 g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha-and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under mu g conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.