Increased ROS generation in subsets of OGG1 knockout fibroblast cells

Attila Bacsi, Grzegorz Chodaczek, Tapas K. Hazra, David Konkel, Istvan Boldogh

Research output: Contribution to journalArticle

36 Scopus citations

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 (HROS cells), while ∼85% of Ogg1-/- cells exhibit physiological levels of ROS (LROS cells). Ogg1-/- cells were sorted based on their DCF fluorescence intensity to obtain LROS and HROS cell cultures. LROS cultures proliferated at a rate comparable to Ogg1+/+ and gradually accumulated cells exhibiting increased ROS and 8-oxoG levels. LROS cells show a 2.8-fold increase in 8-oxoG level vs. HROS cells (7-27-fold). Mitochondria of HROS cells released more H2O2 than LROS 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.

Original languageEnglish (US)
Pages (from-to)637-649
Number of pages13
JournalMechanisms of Ageing and Development
Volume128
Issue number11-12
DOIs
StatePublished - Nov 1 2007

Keywords

  • 8-oxoguanine
  • Mitochondria
  • Ogg1 null fibroblast
  • ROS

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

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