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Mech Ageing Dev. 2007 Nov-Dec;128(11-12):637-49. Epub 2007 Oct 5.

Increased ROS generation in subsets of OGG1 knockout fibroblast cells.

Author information

  • 1Department of Microbiology and Immunology, University of Texas Medical Branch ,Galveston, TX 77555, USA.

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.

PMID:
18006041
[PubMed - indexed for MEDLINE]
PMCID:
PMC2704552
Free PMC Article

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