8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle

Vladimir Vartanian, Jana Tumova, Pawel Dobrzyn, Agnieszka Dobrzyn, Yusaku Nakabeppu, R. Stephen Lloyd, Harini Sampath

Research output: Contribution to journalArticle

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Abstract

Oxidative stress resulting from endogenous and exogenous sources causes damage to cellular components, including genomic and mitochondrial DNA. Oxidative DNA damage is primarily repaired via the base excision repair pathway that is initiated by DNA glycosylases. 8-oxoguanine DNA glycosylase (OGG1) recognizes and cleaves oxidized and ring-fragmented purines, including 8-oxoguanine, the most commonly formed oxidative DNA lesion. Mice lacking the OGG1 gene product are prone to multiple features of the metabolic syndrome, including high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Here, we report that OGG1-deficient mice also display skeletal muscle pathologies, including increased muscle lipid deposition and alterations in genes regulating lipid uptake and mitochondrial fission in skeletal muscle. In addition, expression of genes of the TCA cycle and of carbohydrate and lipid metabolism are also significantly altered in muscle of OGG1-deficient mice. These tissue changes are accompanied by marked reductions in markers of muscle function in OGG1-deficient animals, including decreased grip strength and treadmill endurance. Collectively, these data indicate a role for skeletal muscle OGG1 in the maintenance of optimal tissue function.

LanguageEnglish (US)
Article numbere0181687
JournalPLoS ONE
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017

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DNA Glycosylases
glycosylases
Lipid Metabolism
Metabolism
Muscle
skeletal muscle
Skeletal Muscle
Lipids
Muscles
muscles
metabolism
mice
DNA
lipids
endogenous sources
Mitochondrial Dynamics
exogenous sources
Purines
Genes
fatty liver

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Vartanian, V., Tumova, J., Dobrzyn, P., Dobrzyn, A., Nakabeppu, Y., Lloyd, R. S., & Sampath, H. (2017). 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. PLoS ONE, 12(7), [e0181687]. DOI: 10.1371/journal.pone.0181687

8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. / Vartanian, Vladimir; Tumova, Jana; Dobrzyn, Pawel; Dobrzyn, Agnieszka; Nakabeppu, Yusaku; Lloyd, R. Stephen; Sampath, Harini.

In: PLoS ONE, Vol. 12, No. 7, e0181687, 01.07.2017.

Research output: Contribution to journalArticle

Vartanian, V, Tumova, J, Dobrzyn, P, Dobrzyn, A, Nakabeppu, Y, Lloyd, RS & Sampath, H 2017, '8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle' PLoS ONE, vol. 12, no. 7, e0181687. DOI: 10.1371/journal.pone.0181687
Vartanian V, Tumova J, Dobrzyn P, Dobrzyn A, Nakabeppu Y, Lloyd RS et al. 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. PLoS ONE. 2017 Jul 1;12(7). e0181687. Available from, DOI: 10.1371/journal.pone.0181687
Vartanian, Vladimir ; Tumova, Jana ; Dobrzyn, Pawel ; Dobrzyn, Agnieszka ; Nakabeppu, Yusaku ; Lloyd, R. Stephen ; Sampath, Harini. / 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. In: PLoS ONE. 2017 ; Vol. 12, No. 7.
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