8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho-GTPase activation and smooth muscle α-actin polymerization.

8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho-GTPase activation and smooth muscle α-actin polymerization. Free Radic Biol Med. 2014 Mar 26; Authors: Luo J, Hosoki K, Bacsi A, Radak Z, Hegde ML, Sur S, Hazra TK, Brasier AR, Ba X, Boldogh I Abstract Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-oxo-7,8-dihydro-guanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, while its etiological relevance is unclear. 8-oxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)- initiated DNA base excision repair pathway (BER). OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho-GTPase and mediate changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs, and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting and microscopic imaging. We found that OGG1 physically intercats with Rho-GTPase, and in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediated smooth muscle α-actin (α-SMA) polymerization into stress fiber and increased the level of α-SMA in insoluble cellular...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research