Role of the DNA repair glycosylase OGG1 in the activation of murine splenocytes

• Verfasst von: Seifermann, Marco [VerfasserIn]
• Verfasst von: Niehrs, Christof [VerfasserIn]
• Titel: Role of the DNA repair glycosylase OGG1 in the activation of murine splenocytes
• Verf.angabe: Marco Seifermann, Alexander Ulges, Tobias Bopp, Svetlana Melcea, Andrea Schäfer, Sugako Oka, Yusaku Nakabeppu, Arne Klungland, Christof Niehrs, Bernd Epe
• Umfang: 8 S.
• Fussnoten: Available online 12 August 2017 ; Gesehen am 29.06.2018
• Titel Quelle: Enthalten in: DNA repair
• Jahr Quelle: 2017
• Band/Heft Quelle: 58(2017), S. 13-20
• ISSN Quelle: 1568-7856
• DOI: doi:10.1016/j.dnarep.2017.08.005
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1577045645

Abstract

OGG1 (8-oxoguanine-DNA glycosylase) is the major DNA repair glycosylase removing the premutagenic DNA base modification 8-oxo-7,8-dihydroguanine (8-oxoG) from the genome of mammalian cells. In addition, there is accumulating evidence that OGG1 and its substrate 8-oxoG might function in the regulation of certain genes, which could account for an attenuated immune response observed in Ogg1−/− mice in several settings. Indications for at least two different mechanisms have been obtained. Thus, OGG1 could either act as an ancillary transcription factor cooperating with the lysine-specific demethylase LSD1 or as an activator of small GTPases. Here, we analysed the activation by lipopolysaccaride (LPS) of primary splenocytes obtained from two different Ogg1−/− mouse strains. We found that the induction of TNF-α expression was reduced in splenocytes (in particular macrophages) of both Ogg1−/− strains. Notably, an inhibitor of LSD1, OG-L002, reduced the induction of TNF-α mRNA in splenocytes from wild-type mice to the level observed in splenocytes from Ogg1−/− mice and had no influence in the latter cells. In contrast, inhibitors of the MAP kinases p38 and JNK as well as the antioxidant N-acetylcysteine attenuated the LPS-stimulated TNF-α expression both in the absence and presence of OGG1. The free base 8-oxo-7,8-dihydroguanine had no influence on the TNF-α expression in the splenocytes. The data demonstrate that OGG1 plays a role in an LSD1-dependent pathway of LPS-induced macrophage activation in mice.