Increased ROS generation in subsets of OGG1 knockout fibroblast cells.

Abstract

Oxoguanine DNA glycosylase (OGG1) is a major base excision repair protein responsible for excision of the mutagenic 8-oxoguanosine (8-oxoG) lesions from the genome. Despite OGG1's importance, the moderate phenotype of Ogg1-null (Ogg1(-/-)) mice is not well understood. This study addresses a mechanism by which Ogg1(-/-) cells limit accumulation of 8-oxoG in their genome. Our data reveal that a subset of Ogg1(-/-) cells shows higher ROS levels ((H)ROS cells), while approximately 85% of Ogg1(-/-) cells exhibit physiological levels of ROS ((L)ROS cells). Ogg1(-/-) cells were sorted based on their DCF fluorescence intensity to obtain (L)ROS and (H)ROS cell cultures. (L)ROS cultures proliferated at a rate comparable to Ogg1(+/+) and gradually accumulated cells exhibiting increased ROS and 8-oxoG levels. (L)ROS cells show a 2.8-fold increase in 8-oxoG level vs. (H)ROS cells (7-27-fold). Mitochondria of (H)ROS cells released more H(2)O(2) than (L)ROS and Ogg1(+/+) cells and were eliminated by apoptotic-like processes. These findings suggest that in the absence of OGG1, a surveillance system is activated that removes cells with extreme 8-oxoG levels from Ogg1(-/-) cultures. Whether similar mechanisms exists in tissues of Ogg1(-/-) mice is the focus of future investigations.

050100200920102011201220132014201520162017
Citations per Year

202 Citations

Semantic Scholar estimates that this publication has 202 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Bacsi2007IncreasedRG, title={Increased ROS generation in subsets of OGG1 knockout fibroblast cells.}, author={Attila Bacsi and Grzegorz Chodaczek and Tapas K Hazra and David A . Konkel and Istvan Boldogh}, journal={Mechanisms of ageing and development}, year={2007}, volume={128 11-12}, pages={637-49} }