Abstract 1674 Actin dynamics influence the activation of NOX5 superoxide production via phosphorylation

NADPH oxidases (NOXs) are a family of 7 transmembrane signaling proteins that produce reactive oxygen species (ROS).NOX5 is the most recently discovered NOX and the only member of the NOX family that is not present in mice and rats.It creates a superoxide burst in response to an increase in intracellular calcium.Disturbances or irregularities in ROS production can lead to conditions such as cancer and cardiovascular disease.NOX5 is an important signaling enzyme involved in many cellular processes and has been shown to oxidatively modify actin.We have found that changes in actin dynamics, specifically the stabilization of F-actin, promote NOX5 superoxide production in the cell, even in the absence of added intracellular calcium.It has also been shown previously that phosphorylation of NOX5 by kinases including PKCa can stimulate superoxide by NOX5 in the absence of increases in intracellular calcium.Activation of PKCa in conjunction with F-actin stabilization in HEK293 cells stably expressing NOX5 showed an increased rate of superoxide production.However, when PKCa was knocked down in those cells, F-actin stabilization alone slightly increased NOX5 superoxide production.Therefore, we believe that PKCa may be competing with another kinase, such as ABL1, to interact with and activate NOX5, and this interaction is promoted by F-actin stabilization.