ArticleProceedings of the National Academy of Sciences of the United States of America2014
Aag-initiated base excision repair promotes ischemia reperfusion injury in liver, brain, and kidney.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting DNA Damage and Repair Pathways in Cerebral Ischemic Stroke: From Bench to Bedside.Translational stroke research · 2026Review
- OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts.Nature communications · 2025Article
- Telomeres and SIRT1 as Biomarkers of Gamete Oxidative Stress, Fertility, and Potential IVF Outcome.International journal of molecular sciences · 2024Review
- Advancing stroke therapy: the potential of MOF-based nanozymes in biomedical applications.Frontiers in bioengineering and biotechnology · 2024Review
- NADJournal of cellular and molecular medicine · 2022Article
- Innovations and Emerging Therapies to Combat Renal Cell Damage: NADAntioxidants & redox signaling · 2021Review
- Article
- Article
- Versatile cell-based assay for measuring DNA alkylation damage and its repair.Scientific reports · 2021Article
- Base excision repair causes age-dependent accumulation of single-stranded DNA breaks that contribute to Parkinson disease pathology.Cell reports · 2021Article
- Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice.Cell reports · 2021Article
- Propofol Mediated Protection of the Brain From Ischemia/Reperfusion Injury Through the Regulation of Microglial Connexin 43.Frontiers in cell and developmental biology · 2021Article
- Article
- Inflammation-induced DNA damage, mutations and cancer.DNA repair · 2019Review
- Mitochondria in the signaling pathways that control longevity and health span.Ageing research reviews · 2019Review
- TFEB-driven lysosomal biogenesis is pivotal for PGC1α-dependent renal stress resistance.JCI insight · 2019Article
- Review
- The impact of oxidative DNA damage and stress on telomere homeostasis.Mechanisms of ageing and development · 2019Review
- De novo NADNature medicine · 2018Article
- Oxidative stress and DNA damage after cerebral ischemia: Potential therapeutic targets to repair the genome and improve stroke recovery.Neuropharmacology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Inflammation is accompanied by the release of highly reactive oxygen and nitrogen species (RONS) that damage DNA, among other cellular molecules. Base excision repair (BER) is initiated by DNA glycosylases and is crucial in repairing RONS-induced DNA damage; the alkyladenine DNA glycosylase (Aag/Mpg) excises several DNA base lesions induced by the inflammation-associated RONS release that accompanies ischemia reperfusion (I/R). Using mouse I/R models we demonstrate that Aag(-/-) mice are significantly protected against, rather than sensitized to, I/R injury, and that such protection is observed across three different organs. Following I/R in liver, kidney, and brain, Aag(-/-) mice display decreased hepatocyte death, cerebral infarction, and renal injury relative to wild-type. We infer that in wild-type mice, Aag excises damaged DNA bases to generate potentially toxic abasic sites that in turn generate highly toxic DNA strand breaks that trigger poly(ADP-ribose) polymerase (Parp) hyperactivation, cellular bioenergetics failure, and necrosis; indeed, steady-state levels of abasic sites and nuclear PAR polymers were significantly more elevated in wild-type vs. Aag(-/-) liver after I/R. This increase in PAR polymers was accompanied by depletion of intracellular NAD and ATP levels plus the translocation and extracellular release of the high-mobility group box 1 (Hmgb1) nuclear protein, activating the sterile inflammatory response. We thus demonstrate the detrimental effects of Aag-initiated BER during I/R and sterile inflammation, and present a novel target for controlling I/R-induced injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.