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Role of the DNA repair glycosylase OGG1 in the activation of murine splenocytes
- Source :
- DNA Repair. 58:13-20
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
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.
- Subjects :
- 0301 basic medicine
Guanine
DNA Repair
DNA repair
p38 mitogen-activated protein kinases
Biology
Biochemistry
DNA Glycosylases
Mice
03 medical and health sciences
Animals
Molecular Biology
Transcription factor
Tumor Necrosis Factor-alpha
Kinase
Activator (genetics)
Macrophages
DNA
Cell Biology
Base excision repair
Molecular biology
030104 developmental biology
Gene Expression Regulation
DNA glycosylase
Tumor necrosis factor alpha
Spleen
DNA Damage
Transcription Factors
Subjects
Details
- ISSN :
- 15687864
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- DNA Repair
- Accession number :
- edsair.doi.dedup.....5e672467687362e47c8f6d563644af49