ArticleCell death & disease2016
Lithium promotes DNA stability and survival of ischemic retinal neurocytes by upregulating DNA ligase IV.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Lithium as a Potential Senostatic Agent in Central Nervous System Aging and Bipolar Disorder.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Genotype epigenome phenotype integration reveals peripheral immune contributions to type I bipolar disorder.Nature communications · 2026Article
- Anti-Apoptotic and Neurite-Protective Nanomedicine Augments Embryonic Stem Cells-Derived Retinal Ganglion Cell Transplantation in Glaucoma Recovery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PKA prevents the resection of DNA double-strand breaks and favours nonhomologous end-joining.Scientific reports · 2025Article
- Lithium Chloride Exerts Anti-Inflammatory and Neuroprotective Effects by Inhibiting Microglial Activation in LPS-Induced Retinal Injury.Investigative ophthalmology & visual science · 2023Article
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- Gata3 Silencing Is Involved in Neuronal Differentiation and Its Abnormal Expression Impedes Neural Activity in Adult Retinal Neurocytes.International journal of molecular sciences · 2022Article
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- Glycogen synthase kinase-3β inhibitor SB216763 promotes DNA repair in ischemic retinal neurons.Neural regeneration research · 2021Article
- Inhibition of non-homologous end joining of gamma ray-induced DNA double-strand breaks by cAMP signaling in lung cancer cells.Scientific reports · 2020Article
- Crx Is Posttranscriptionally Regulated by Light Stimulation in Postnatal Rat Retina.Frontiers in cell and developmental biology · 2020Article
- Artesunate induces mitochondria-mediated apoptosis of human retinoblastoma cells by upregulating Kruppel-like factor 6.Cell death & disease · 2019Article
- Attenuating the DNA damage response to double-strand breaks restores function in models of CNS neurodegeneration.Brain communications · 2019Article
- Interferon Regulatory Factor 3 Deficiency Induces Age-Related Alterations of the Retina in Young and Old Mice.Frontiers in cellular neuroscience · 2019Article
- GSK3β negatively regulates TRAX, a scaffold protein implicated in mental disorders, for NHEJ-mediated DNA repair in neurons.Molecular psychiatry · 2018Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurons display genomic fragility and show fragmented DNA in pathological degeneration. A failure to repair DNA breaks may result in cell death or apoptosis. Lithium protects retinal neurocytes following nutrient deprivation or partial nerve crush, but the underlying mechanisms are not well defined. Here we demonstrate that pretreatment with lithium protects retinal neurocytes from ischemia-induced damage and enhances light response in rat retina following ischemia-reperfusion injury. Moreover, we found that DNA nonhomologous end-joining (NHEJ) repair is implicated in this process because in ischemic retinal neurocytes, lithium significantly reduces the number of γ-H2AX foci (well-characterized markers of DNA double-strand breaks in situ) and increases the DNA ligase IV expression level. Furthermore, we also demonstrate that nuclear respiratory factor 1 (Nrf-1) and phosphorylated cyclic AMP-response element binding protein-1 (P-CREB1) bind to ligase IV promoter to cause upregulation of ligase IV in neurocytes. The ischemic upregulation of Nrf-1 and lithium-induced increase of P-CREB1 cooperate to promote transcription of ligase IV. Short hairpin RNAs against Nrf-1 and CREB1 could significantly inhibit the increase in promoter activity and expression of ligase IV observed in the control oligos following lithium treatment in retinal neurocytes. More importantly, ischemic stimulation triggers the expression of ligase IV. Taken together, our results thus reveal a novel mechanism that lithium offers neuroprotection from ischemia-induced damage by enhancing DNA NHEJ repair.
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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.