Estudios científicos

Phosphoinositide 3-kinase is a novel target of piceatannol for inhibiting PDGF-BB-induced proliferation and migration in human aortic smooth muscle cells

Abstract:

AIMS: Abnormal migration and proliferation of human aortic smooth muscle cells (HASMCs) to the intima causes intimal thickening of the aorta, which is strongly related to the development of atherosclerosis. Previous studies have suggested that red wine polyphenols, particularly resveratrol, have great protective effects against cardiovascular diseases. Here, we compared the anti-atherosclerotic effect of piceatannol, a metabolite of resveratrol, and its underlying mechanisms. METHODS AND RESULTS: We demonstrated that piceatannol inhibited platelet-derived growth factor (PDGF)-BB-induced cell migration using a modified Boyden chamber assay and wound healing assay. Western blot analysis showed that PDGF-BB-induced phosphorylation of Akt, p70S6K, and p38 was inhibited by piceatannol, but not resveratrol. In vitro and ex vivo phosphoinositide 3-kinase (PI3K) assays demonstrated that piceatannol suppressed PI3K activity more effectively than resveratrol. PDGF-BB-induced migration and proliferation of HASMCs were inhibited by treatment with a commercial PI3K inhibitor, LY294002. Both in vitro and ex vivo pull-down assays revealed that piceatannol directly binds with sepharose 4B-PI3K beads in an ATP-competitive manner. CONCLUSION: The results of the present study demonstrate that piceatannol directly binds with PI3K in an ATP-competitive manner and suppresses PI3K activity with anti-atherosclerotic effects.

Comentarios divulgativos:

La migración y proliferación de las células musculares aórticas (HASMCs) es una de las principales causas de que la aorta se estreche lo cual está intimamente relacionado con el desarrollo de la aterosclerosis. Estudios previos sugieren que los polifenoles del vino tinto, particularmente el resveratrol tienen un efecto protector contra las enfermedades cardiovasculares. En este estudio se compara el efcto antiesclerotico del picetanol, el cual es un metabolito del resveratrol.

Los resultados muestran que el picetanol se une directamente a PI3K como un competidor del ATP y suprime su actividad y por tanto provocando los efectos antiescleroticos.