首页> 外文期刊>Endothelium: Journal of endothelial cell research >Mechanisms of endothelial survival under shear stress.
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Mechanisms of endothelial survival under shear stress.

机译:剪切应力作用下内皮细胞存活的机制。

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Endothelial cells (ECs) are exposed to cytotoxic reactive oxygen species and oxidation products of NO, yet they are characterized by low apoptotic rates and have an average life span of many years. EC exposure to flow has been shown to downregulate cell cycle-related genes and cause cytoskeletal rearrangement. We hypothesized that exposure to flow also causes molecular and physiological changes that induce antioxidant properties in ECs. We used cDNA array expression profiling and protein analysis to study the responses of human ECs exposed to flow in a hollow fiber apparatus or the same ECs grown under static conditions. Our results show that shear-induced synchronized expression of processes control oxidant production; these changes included upregulation of NADH-producing enzymes (Krebs cycle dehydrogenases and glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) accompanied by simultaneous decrease in NADH-depleting pathways (e.g., lactate dehydrogenase [LDH]) and diminished production of lactate. Exposure to flow upregulated cytoskeletal genes. Our results suggest that, in addition to inhibition of cell cycle, exposure to flow influences ECs by controlling expression of enzymes involved in the generation of antioxidant intermediates and in adaptive control of cell shape. These changes may explain longevity and antioxidant efficiency of ECs and may provide insight in mechanisms leading to pathological conditions such as arteriosclerosis.
机译:内皮细胞(ECs)暴露于细胞毒性的活性氧和NO的氧化产物中,但其凋亡率低,平均寿命长达数年。已经表明,EC暴露于血流中会下调细胞周期相关基因并引起细胞骨架重排。我们假设暴露于流动也会引起分子和生理变化,从而诱发EC的抗氧化特性。我们使用cDNA阵列表达谱分析和蛋白质分析来研究暴露在中空纤维装置中的人EC或在静态条件下生长的相同EC的响应。我们的结果表明,剪切诱导的过程同步表达控制着氧化剂的产生。这些变化包括上调产生NADH的酶(克雷布斯循环脱氢酶和3-磷酸甘油醛脱氢酶[GAPDH]),同时减少NADH的消耗途径(例如乳酸脱氢酶[LDH])和减少乳酸的产生。暴露于流量上调的细胞骨架基因。我们的结果表明,除了抑制细胞周期外,暴露于流动还会通过控制参与抗氧化剂中间体的产生和细胞形状适应性控制的酶的表达来影响EC。这些变化可以解释EC的寿命和抗氧化效率,并且可以提供导致诸如动脉硬化等病理状况的机制的见解。

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