Actin stabilization by jasplakinolide affects the function of bone marrow-derived late endothelial progenitor cells.
Actin stabilization by jasplakinolide affects the function of bone marrow-derived late endothelial progenitor cells.
复制标题
jasplakinolide 稳定肌动蛋白会影响骨髓来源的晚期内皮祖细胞的功能。
DOI：
10.1371/journal.pone.0050899
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cheng M
中科院分区：
文献类型：
--
作者：
Zhang X;Cui X;Cheng L;Guan X;Li H;Li X;Cheng M
骨髓来源的内皮祖细胞（EPCs），特别是晚期EPCs，在内皮细胞的维持和修复以及出生后血管生成中起着关键作用。尽管肌动蛋白细胞骨架被认为是控制干细胞功能和调节的调节剂，但其在EPCs，特别是晚期EPCs功能中的作用仍然知之甚少。骨髓来源的晚期EPCs用jasplakinaline处理，jasplakinaline是一种稳定肌动蛋白丝的化合物。随后在体外检测细胞凋亡、增殖、粘附、迁移、管状形成、一氧化氮（NO）产生和内皮NO合酶（eNOS）磷酸化。此外，内皮祖细胞局部注入新鲜球囊损伤的颈动脉，并在14天后评估再内皮化能力。Jasplakinhibitors以浓度和时间依赖的方式影响晚期EPCs的肌动蛋白分布，中等浓度（100 nmol/l）的Jasplakinhibitors直接稳定晚期EPCs的肌动蛋白丝。Jasplakin对内皮细胞的肌动蛋白稳定作用增强了VEGF剥夺诱导的晚期EPC凋亡，并显著抑制了晚期EPC的增殖、粘附、迁移和管腔形成。此外，jasplakin减弱了移植EPCs在体内损伤动脉段的再内皮化能力。然而，eNOS磷酸化和NO的产生增加，在晚期EPCs与jasplakinantine处理。NO供体硝普钠（SNP）挽救了茉莉花内酯应激晚期EPCs的功能活性，而内皮NO合酶抑制剂L-NAME导致茉莉花内酯诱导的晚期EPCs进一步功能障碍。中等浓度的jasplakin导致肌动蛋白丝的积累，增强细胞因子剥夺诱导的凋亡，并在体外和体内损害晚期EPCs的增殖和功能。NO供体逆转这些损伤，表明NO相关机制在茉莉花内酯诱导的EPC下调中的作用。因此，肌动蛋白细胞骨架可能在调节晚期EPC功能中发挥关键作用。
Bone marrow-derived endothelial progenitor cells (EPCs), especially late EPCs, play a critical role in endothelial maintenance and repair, and postnatal vasculogenesis. Although the actin cytoskeleton has been considered as a modulator that controls the function and modulation of stem cells, its role in the function of EPCs, and in particular late EPCs, remains poorly understood. Bone marrow-derived late EPCs were treated with jasplakinolide, a compound that stabilizes actin filaments. Cell apoptosis, proliferation, adhesion, migration, tube formation, nitric oxide (NO) production and endothelial NO synthase (eNOS) phosphorylation were subsequently assayed in vitro. Moreover, EPCs were locally infused into freshly balloon-injured carotid arteries, and the reendothelialization capacity was evaluated after 14 days. Jasplakinolide affected the actin distribution of late EPCs in a concentration and time dependent manner, and a moderate concentration of (100 nmol/l) jasplakinolide directly stabilized the actin filament of late EPCs. Actin stabilization by jasplakinolide enhanced the late EPC apoptosis induced by VEGF deprivation, and significantly impaired late EPC proliferation, adhesion, migration and tube formation. Furthermore, jasplakinolide attenuated the reendothelialization capacity of transplanted EPCs in the injured arterial segment in vivo. However, eNOS phosphorylation and NO production were increased in late EPCs treated with jasplakinolide. NO donor sodium nitroprusside (SNP) rescued the functional activities of jasplakinolide-stressed late EPCs while the endothelial NO synthase inhibitor L-NAME led to a further dysfunction induced by jasplakinolide in late EPCs. A moderate concentration of jasplakinolide results in an accumulation of actin filaments, enhancing the apoptosis induced by cytokine deprivation, and impairing the proliferation and function of late EPCs both in vitro and in vivo. NO donor reverses these impairments, suggesting the role of NO-related mechanisms in jasplakinolide-induced EPC downregulation. Actin cytoskeleton may thus play a pivotal role in regulating late EPC function.
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影响因子：
3.7
作者：
Knecht DA;LaFleur RA;Kahsai AW;Argueta CE;Beshir AB;Fenteany G
通讯作者：
Fenteany G
影响因子：
3.7
作者：
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7.2
作者：
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82.9
作者：
Aicher, A;Heeschen, C;Dimmeler, S
通讯作者：
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影响因子：
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作者：
Funcke, Fabienne;Hoyer, Heike;Bloch, Wilhelm
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