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001-es BibID:BIBFORM055557
Első szerző:Luo, Jixian
Cím:8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization / Jixian Luo, Koa Hosoki, Attila Bacsi, Zsolt Radak, Muralidhar L. Hegde, Sanjiv Sur, Tapas K. Hazra, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:2014
ISSN:0891-5849
Megjegyzések:Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. 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 mediates 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 interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates ?-smooth muscle actin (?-SMA) polymerization into stress fibers and increases the level of ?-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Free Radical Biology and Medicine. - 73 (2014), p. 430-438. -
További szerzők:Hosoki, Koa Bácsi Attila (1967-) (immunológus) Radák Zsolt Hegde, Muralidhar L. Sur, Sanjiv Hazra, Tapas K. Brasier, Allan R. Ba, Xueqing Boldogh István
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