Abstract
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.