Dynamin 2 is involved in Angiotensin II‐induced NADPH oxidase activity mediated through cortactin in vascular smooth muscle cells

Abstract

Although the actin cytoskeleton has been implicated in the control of NADPH oxidase activation induced by angiotensin II (Ang II), very little is known about the detailed molecular mechanisms. The dynamin family of large GTPases has been suggested in the formation of nascent vesicles in endocytic pathways. However, there is no report about the role of the large GTPase dynamin 2 (Dyn2) on the activity of NADPH oxidase induced by Ang II in vascular smooth muscle cells (VSMC). In this study we found that Dyn2 was colocalized with cortactin, the actin‐binding protein, by immunofluorencence. By performing immunoprecipitation, Ang II stimulation enhanced the association between Dyn2 and cortactin. Importantly, both cortactin siRNA and Dyn2 siRNA significantly inhibited Ang II‐induced ROS production, whereas cytochalasin D and latrunculin A suppressed the ROS formation by Ang II. Furthermore, Dyn2 siRNA significantly inhibited Ang II‐stimulated redox‐sensitive Akt phosphorylation without affecting redox‐insensitive ERK1/2 phosphorylation. These findings provide the first demonstration that Dyn2 is involved in Ang II‐stimulation NADPH oxidase activation mediated through cortactin, which may play an important role in temple‐spatial role in ROS‐dependent Ang II signaling in vascular smooth muscle cells.