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Nicotinic acid affects cytoskeleton remodeling via increasing the activity of gelsolin.
Cytoskeleton ( IF 2.9 ) Pub Date : 2019-10-11 , DOI: 10.1002/cm.21563
Xiang Su 1 , Haizhen Ni 1 , Wenxu Jin 1 , Lemen Pan 1
Affiliation  

Our previous research has demonstrated that nicotinic acid (NA) might suppress the angiogenesis by modulating the expression of angiogenesis factors and promoting the cytoskeleton remodeling. However, the underlying mechanism need to be further elucidated. The intracellular Ca2+ concentration was measured by a [Ca2+] detection kit. The F‐actin depolymerization was shown by immunofluorescence staining. The protein levels of F‐actin and G‐actin were determined by Western blot. The effects of NA treatment on the gelsolin‐PI3Kα (p110α) interaction were investigated by co‐immunoprecipitation (Co‐IP). NA treatment caused an initial drop and then induced a significant increase in [Ca2+] with a time and dose dependent manner. In addition, NA promoted the depolymerization of F‐actin and knockdown of gelsolin substantially rescued the effects caused by NA treatment. NA treatment significantly inhibited the interaction between phosphoinositide 3‐kinase (PI3K) α (p110α) and gelsolin and addition of phosphatidylinositol (3,4,5)‐triphosphate (PIP3) increased the protein level of F‐actin and rescued the F/G‐actin ratio. In conclusion, our results indicated NA treatment could interfere with the ability of PI3Kα (p110α) to inhibit the activity of gelsolin by decomposing PIP2 to produce PIP3, thereby increasing the activity of gelsolin, which ultimately acted on the remodeling of the cytoskeleton and exerted an inhibitory effect on angiogenesis.

中文翻译:

烟酸通过增加凝溶胶蛋白的活性影响细胞骨架的重塑。

我们以前的研究表明烟酸(NA)可能通过调节血管生成因子的表达并促进细胞骨架重塑来抑制血管生成。但是,需要进一步阐明其基本机制。细胞内Ca 2+浓度通过[Ca 2+ ]检测试剂盒测定。免疫荧光染色显示F-肌动蛋白解聚。F-肌动蛋白和G-肌动蛋白的蛋白质水平通过蛋白质印迹法测定。通过共免疫沉淀(Co-IP)研究了NA处理对凝溶胶蛋白-PI3Kα(p110α)相互作用的影响。NA处理导致最初的下降,然后引起[Ca 2+用时间和剂量依赖的方式。此外,NA促进了F-肌动蛋白的解聚,凝溶胶蛋白的敲低基本上挽救了NA治疗所引起的影响。NA处理可显着抑制磷酸肌醇3激酶(PI3K)α(p110α)与凝溶胶蛋白之间的相互作用,添加磷脂酰肌醇(3,4,5)-三磷酸(PIP3)可提高F-肌动蛋白的蛋白水平并拯救F / G -肌动蛋白比率。总之,我们的结果表明,NA处理可能会通过分解PIP2产生PIP3来干扰PI3Kα(p110α)抑制凝溶胶蛋白的活性,从而增加凝溶胶蛋白的活性,从而最终影响细胞骨架的重塑并发挥作用。对血管生成的抑制作用。
更新日期:2019-10-11
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