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At least 19 recordsLinked to original sources
PubMed2026

Oxidative Damage Fine-Tunes G-Quadruplex Structures in Human Gene Promoters.

Oxidative damage can convert guanine (G) into 8-oxoguanine (O8G), resulting in altered gene expression and genome instability. However, the underlying molecular mechanisms remain poorly understood. Herein, we show that the NEIL3 gene proximal promoter sequence forms a mixture of parallel and hybrid G-quadruplex structures (NEIL3-G4s), exhibiting intrinsic structural polymorphism. Strikingly, site-specific O8G modifications significantly reduce this polymorphism, promoting the stabilization of either the parallel or the (3+1) hybrid-1 G4 topology. A single G-to-O8G substitution is sufficient to trigger a clear structural transition from the parallel to the (3+1) hybrid-1 G4, highlighting the profound impact of O8G on G4-mediated epigenetic regulation. We have determined the NMR solution structures of both native and O8G-modified NEIL3-G4s, providing mechanistic insights into how O8G induces specific G4 structural rearrangements. Functional analysis demonstrates that both forms of NEIL3-G4s can form in extended DNA contexts and inhibit DNA polymerase activity. Under oxidative stress, the formation of NEIL3-G4s correlates with elevated NEIL3 gene expression, suggesting that they play a role as sensors of oxidative damage and function as molecular switches for gene upregulation. Collectively, these findings underscore the crucial role of O8G-induced G4 structural plasticity in the cellular response to oxidative stress and in regulating gene expression.

G-Quadruplexes↗
PubMed2026

CaCl2 Priming Boosts Salinity-Alkalinity Tolerance in Germinating Soybean by Reducing DNA Oxidative Damage and Enhancing Ca2+ -ROS Signaling Crosstalk.

Soybean (Glycine max) seed germination is highly sensitive to saline-alkaline stress. Seed priming represents an effective strategy to mitigate its detrimental effects. However, the optimal priming conditions (agent, concentration, duration) and the underlying molecular mechanisms remain poorly understood. This study investigated the effects of priming with distilled water (Control), calcium chloride (CaCl2), melatonin (MT), and proline (Pro) under saline-alkaline stress on soybean seed germination and the molecular basis of enhanced tolerance. Evaluation of ten germination-related parameters revealed that priming with 100 mM CaCl2 for 12 h significantly enhanced the germination rate. Physiological analyses demonstrated that CaCl2 priming effectively reduced reactive oxygen species (ROS) accumulation by increasing the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), while decreasing malondialdehyde (MDA) content. Furthermore, CaCl2 priming activated the Ca2+ signaling pathway by increasing radicle Ca2+ content and upregulating the expression levels of Ca2+ signaling-related genes (e.g., GmCAM7, GmCNGC2, GmCNGC19, GmMPK2, and GmMKK2). Additionally, CaCl2 priming significantly enhanced DNA damage repair capacity of soybean cultivars with differing saline-alkaline tolerance. This was manifested by reduced DNA oxidative damage and decreased random amplified polymorphic DNA (RAPD) polymorphism, thereby enhancing genomic stability and alleviating cell cycle arrest. These findings deepen our understanding of the complex regulatory role of calcium signaling in plant abiotic stress responses and provide important novel theoretical insights for improving crop resilience.

Glycine max↗
PubMed2025

Transposition element MERVL regulates DNA demethylation through TET3 in oxidative-damaged mouse preimplantation embryos.

Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage and commonly serves as an indicator of embryonic totipotency. However, its precise role in embryo development remains mysterious. We utilized DRUG-seq to investigate the effects of oxidative damage on genes and TEs expression. Our findings revealed that exposure to hydrogen peroxide (H2O2) could induce DNA damage, apoptosis, and incomplete DNA demethylation in embryos, which were potentially associated with MERVL expression. To further explore its function, antisense nucleotides (ASO) targeting MERVL were constructed to knockdown the expression in early embryos. Notably, this knockdown led to the occurrence of DNA damage and apoptosis as early as the 2-cell stage, consequently reducing the number of embryos that could progress to the blastocyst stage. Moreover, we discovered that MERVL exerted an influence on the reprogramming of embryonic DNA methylation. In MERVL-deficient embryos, the activity of the DNA demethylase ten-eleven translocation 3 (TET3) was suppressed, resulting in impaired demethylation when compared to normal development. This impairment might underpin the mechanism that impacts embryonic development. Collectively, our study not only verified the crucial role of MERVL in embryonic development but also probed its regulatory function in DNA methylation reprogramming, thereby laying a solid foundation for further investigations into MERVL's role.

Animals↗
PubMedDate not supplied

Oxidative damage to the erythrocyte induced by sodium chlorite, in vitro.

The ability of sodium chlorite to react with constituents of the erythrocyte, in vitro, was examined and compared to that of nitrite. The oxidative damage resulting from chlorite is fundamentally different from that of nitrite. Nitrite is slightly more potent as an oxidant of hemoglobin, while chlorite appears to be less specific in its oxidation of cellular constituents. Unlike nitrite, chlorite was found to deplete erythrocyte glutathione, which was accompanied by an increase in hydrogen peroxide generation. Chlorite also produced substantial changes in erythrocyte membrane morphology. These effects of chlorite are characteristic of compounds that produce oxidant-induced hemolytic anemia in vivo.

Anaerobiosis↗
PubMed2026

iMSC-derived extracellular vesicles and their miRNA cargo influence inflammation and oxidative damage in an in vitro osteoarthritis model.

Osteoarthritis is a multifactorial chronic joint disease characterized by progressive cartilage degradation and inflammation. Since there is no effective cure, emerging therapeutic approaches, such as mesenchymal stromal cells (MSCs) transplantation, are currently under investigation. However, the clinical translation of MSC-based therapies is hampered by several limitations, such as donor-dependent variability and heterogeneity related to tissue sources. To address these issues, MSCs derived from induced pluripotent stem cells (iMSCs) have been proposed as a more standardized and scalable alternative. Due to the risks of cell-based therapy, extracellular vesicles (EVs), particularly iMSC-EVs (iEVs), could represent a promising cell-free approach for OA treatment. The present study aimed at characterizing iMSC-derived EVs and evaluating their functional role in modulating inflammatory responses and redox balance in an in vitro OA model. Notably, recent evidence highlights the central role of EV-encapsulated microRNAs (EV-miRNAs) in mediating these effects. EVs isolated from iMSC conditioned media were characterized, and their miRNA content was analyzed at different culture passages. Selected miRNAs were subsequently assessed for their biological activity in an in vitro OA model, with a focus on their impact on inflammatory mediators and oxidative stress parameters. Specifically, six miRNAs such as hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-29a-3p, hsa-miR-29b-3p, and hsa-miR-29c-3p differentially reflect the anti-inflammatory and antioxidant effects of iMSCs-EVs treatment, suggesting possible synergistic effects. Their combined effect in the in vitro model confirmed their potential modulation in the expression of pro-inflammatory cytokines. Furthermore, their treatment markedly reduced ROS accumulation and oxidative damage, while restoring antioxidant defense systems. These findings support the therapeutic potential of iMSC-derived EVs as a cell-free strategy for OA treatment. The miRNA cargo encapsulated within iEVs appears to play a pivotal role in modulating inflammation and oxidative stress, emphasizing their promise as a novel, minimally invasive approach for disease modification in OA.

MicroRNAs↗
PubMed1975

Excision-repair of 4-nitroquinolin-1-oxide damage responsible for killing, mutation, and cancer.

Excision-repair of DNA base damage produced by 4-nitroquinoline-1-oxide (4NQO) was compared in Escherichia coli, human cells, and mouse cells. Paper chromotography of acid hydrolysates of DNA extracted from cells treated with 3H-labeled 4NQO revealed four peaks; two kinds of 4NQO-guanine adduct, one kind of 4NQO-adenine adduct, and free 4-aminoquinoline-1-oxide (4AQO). About 80% of the initially formed 4NQO-purine adducts were excised from DNA in E. coli uvrA+ cells during 60 min postincubation, but not at all in uvrA- (excisionless for uv damage) cells. Normal human cells excised about 60% of 4NQO-purine adducts during 24 hr postincubation, but xeroderma pigmentosum (excisionless) cells did not. A mouse cell line susceptible to repair of 4NQO-induced pretransformational damage also showed excision-repair ability for the 4NQO adducts. From these and other results, we conclude that the 4NQO-purine adducts and unstable 4NQO-guanine products (which release 4AQO) are, like pyrimidine dimers, repairable by excision-repair universal among E. coli, mouse, and human being, and that unexcised ones are probably the major cause of killing, mutation, and cancer.

4-Nitroquinoline-1-oxide↗
PubMed2026

From oxidative damage to actionable lesion: Telomeric 8-oxoGuanine and OGG1 modulation in aging and disease.

Oxidative stress is widely implicated in aging and chronic disease, but current insights have not led to the definition of a lesion state in the progression of disease or to broad guidance of therapy. So far, reactive oxygen species describe a chemical environment rather than a specific molecular entity. In contrast, 8-oxoG represents a defined oxidative DNA lesion with a defined genomic context impacting biological processes. Here, we propose that 8-oxoG and its downstream repair intermediates define a functionally relevant lesion state at telomeres. At chromosome ends, oxidized guanine can impair replication, activate DNA damage signalling, contribute to telomere attrition and drive senescence. Still, persistent lesions and the toxicity of downstream base excision repair intermediates contribute to this process. This distinction has direct therapeutic consequences: OGG1 inhibitors suppress inflammatory and transcriptional responses, whereas activators and organocatalytic switches promote lesion clearance. We propose that going forward, the choice between these strategies should depend on the dominant lesion state rather than global measures of oxidative stress.

Humans↗
PubMed2026

Peroxiredoxin 1 safeguards the nucleolar genome from oxidative damage.

Peroxiredoxin 1 (PRDX1) is a highly conserved, thiol-dependent peroxidase that rapidly scavenges reactive oxygen species to modulate redox signaling. PRDX1-null mice exhibited genomic instability, shortened life span, and accelerated tumorigenesis, including development of lymphomas, sarcomas, and carcinomas. Despite extensive characterization of these phenotypes, the molecular mechanism by which PRDX1 loss causes genomic instability remains poorly understood. Here, we show that PRDX1 deficiency alters nucleolar morphology, impairs RNA polymerase I (POL-I)-dependent transcription of pre-ribosomal RNAs, and triggers nucleolar genomic instability. This oxidative stress-induced nucleolar dysfunction promotes the stability of secondary DNA structures, such as RNA-DNA hybrids and G-quadruplex DNA, contributing to nucleolar genomic instability. We demonstrate that PRDX1 loss reduces nascent ribosomal RNA (rRNA) levels and impairs rRNA processing, further affecting ribosome biogenesis. Mechanistically, we established that PRDX1 loss triggers activation of the nucleolar DNA damage response characterized by activation of the DNA repair kinase ATM and elevated TCOF1 within the nucleolus. In addition, we observed recruitment of the MRE11-RAD50-NBS1 (MRN) complex subunit NBS1 to ribosomal DNA (rDNA) loci and this was further increased under oxidative stress. NBS1 accumulation correlates with the repression of rDNA transcription by POL-I, potentially delaying rRNA synthesis, and safeguarding the nucleolar genome from further oxidative damage. Collectively, these findings uncover a previously unrecognized, but critical role, for PRDX1 in maintaining nucleolar integrity and ribosomal biogenesis through redox-dependent regulation of rDNA transcription and processing machinery.

Oxidative Stress↗
PubMed1979

Oxidative damage to neutrophils in glutathione synthetase deficiency.

Several episodes of neutropenia were observed in a child with glutathione synthetase deficiency (5-oxoprolinuria). Studies of the patient's glutathione-deficient neutrophils were undertaken to examine the responses of the cells to oxidative stress associated with phagocytosis. The patient's neutrophils contained 10--20% of normal glutathione content. Circulating neutrophils in infection-free periods appeared less mature than normal by morphologic criteria, suggesting increased cell turnover. The cells ingested particles, responded to chemotactic stimuli, and oxidized 1-14C glucose normally. However, following ingestion of particles, the cells accumulated excess hydrogen peroxide compared with normal cells, and showed impaired protein iodination and bacterial killing. Electron micrographs revealed damage to microtubules and membranous structures in the patient's neutrophils during phagocytosis. The level of glutathione in the cells appears inadequate to protect against peroxide generated during normal cell function, and the cells are thus damaged and rendered less effective in bacterial killing. The data provide evidence for a protective role of glutathione in normal neutrophil function.

Chemotaxis, Leukocyte↗
PubMed2026

Protective effects of seminal exosomes on cryopreserved sperm via inhibiting oxidative damage.

This study aimed to explore the protective effect of seminal plasma exosomes (SPEs) on human sperm structure and function during cryopreservation and its potential mechanism. The samples were divided into two groups: the control group was treated solely with sperm cryoprotectant before freezing, while the exosome group was supplemented with SPEs. After cryopreservation and thawing, sperm progressive motility, normal morphological rate, and survival rate were evaluated. Furthermore, PKH67 labeling experiments were performed, and oxidative stress markers as well as energy metabolism indicators in sperm were detected. Subsequent mechanism exploration was conducted via proteomic analysis and protein validation assays. This work reveals that adding SPEs at a concentration of 1 or 2 mg/ml effectively improves sperm progressive motility after cryopreservation. After supplementing with SPEs, sperm glucose levels are reduced and mitochondrial membrane potential is enhanced. Simultaneously, SPEs alleviate oxidative stress by decreasing reactive oxygen species (ROS) and DNA fragment index (DFI) while increasing superoxide dismutase (SOD) activity. Functional annotation of proteomics reveals that 14 of the differentially expressed proteins (DEPs) are associated with sperm motility. Enriched metabolic pathways related to sperm motility and sperm protein validation experiments indicate that the expression of MAPK, p-MAPK, and p-JNK proteins in sperm is higher in the Exosome group than in the Control group. This study provides important theoretical support for the application of SPEs in mitigating cryopreservation damage to sperm by enhancing antioxidant capacity. The specific mechanism may be mediated by the MAPK/p-JNK pathway.

Male↗
PubMed2026

Polystyrene microplastics induce auditory neurotoxicity in mammals: Integrated multi-omics profiling reveals oxidative damage and synaptic molecular dysregulation.

Microplastics (MPs) are ubiquitous environmental pollutants, yet their neurotoxic effects on the auditory system remain poorly understood. This study develops an integrated multi-level analytical framework combining auditory neurophysiology, behavioral assessment, tissue biochemistry, transcriptomics, and proteomics to investigate polystyrene (PS)-MPs-induced auditory neurotoxicity in rats. PS-MPs infiltrate the auditory system and significantly impair auditory processing, with central dysfunction emerging earlier and more prominently than peripheral alterations. Multi-omics analyses reveal coordinated suppression of glutamatergic synapse and Wnt signaling pathways in the cochlear nucleus. Mechanistically, PS-MPs perturb the crosstalk between glutamatergic synaptic and Wnt signaling, promoting AMPA receptor (AMPAR) internalization and potentially affecting synaptic plasticity-related processes and neuronal responsiveness. In parallel, PS-MPs trigger oxidative stress, apoptosis, and glial activation, reflecting pronounced neuroinflammatory and redox imbalance. In primary cochlear nucleus neurons (PCNNs), these mechanisms were further validated in vitro, where activation of Wnt signaling by Wnt3a significantly alleviated oxidative injury and reduced AMPAR internalization. Collectively, these findings provide comprehensive preclinical evidence for the neurotoxic potential of MPs and reveal a previously unrecognized PS-MPs-induced auditory neurotoxicity, although further studies are needed for human relevance. Results from the rat model further implicate Wnt-mediated signaling as a potential modulatory pathway underlying MPs-induced synaptic molecular alterations and redox dysfunction.

Animals↗
PubMed1978

Superoxide dismutase of the eye: relative functions of superoxide dismutase and catalase in protecting the ocular lens from oxidative damage.

1. Activities of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) have been estimated in eye tissues. In rabbit eye, superoxide dismutase is present in corneal epithelium, corneal endothelium, lens, iris, ciliary body and retina. In lens the activity is in capsule epithelium. 2. Copper chelator diethyldithiocarbamate inhibited lens superoxide dismutase in vitro and in vivo in rabbit. 3. H2O2 caused inhibition of superoxide dismutase activity of lens extract, and this inhibition was potentiated by the catalase inhibitor 3-amino-1H-1,2,4-triazole (3-aminotriazole) or NaN3. 3-Aminotriazole or NaN3 had no effect on lens superoxide dismutase. Thus endogenous catalase of lens affords protection to the lens superoxide dismutase from inactivation by H2O2. 4. In rabbit having early cataract (vacuolar stage) induced by feeding-3-aminotriazole, there was a decrease in superoxide dismutase of lens, a fall in ascorbic acid of ocular humors and lens, and a 2--3-Fold increase in H2O2 of aqueous humor and vitreous humor. We conclude that catalase of eye affords protection to the lens from H2O2 and it also protects superoxide dismutase of lens from inactivation by H2O2. Superoxide dismutase, in turn, protects the lens from the superoxide radical, O2.-. It is likely that inhibition of these enzymes may lead to production of the highly reactive oxidant, the hydroxyl radical, under pathological conditions when H2O2 concentration in vivo exceeds physiological limits as in cataract induced by 3-aminotriazole. A scheme of reaction mechanism has been proposed to explain the relative functions of ocular catalase and superoxide dismutase. Such a mechanism may be involved in cataractogenic process in the human.

Amitrole↗
PubMedDate not supplied

Oxidative damage to the erythrocyte induced by sodium chlorite, in vivo.

Sodium chlorite in drinking water was found to produce a slight but compensated anemia in rats after exposure to up to 500 ppm for 90 days. Decreases in hemoglobin, red cell count, and packed cell volume seen after 30 days exposure had substantially recovered by 90 days of treatment. Signs of adaptation remained in that 2,3-diphosphoglyceric acid concentrations in the red cell remained elevated after 90 days exposure to 50 and 100 ppm CIO2-. However, dose-related decreases in erythrocyte glutathione levels, detected at chlorite levels as low as 50 ppm, remained decreased after 90 days exposure. While no other signs of overt toxicity were observed, the fact that hemolytic anemia was involved was confirmed by an increased turnover of red cells in cats exposed to CIO2-. Chlorite-induced decreases in glutathione in vivo were demonstrated to enhance formation of hydrogen peroxide when treated further with chlorite in vitro. Consequently, before a comprehensive determination of the hazards of chlorite in water can b: made, particular attention must be paid to individuals sensitive to hemolytic anemia.

Animals↗
PubMed1979

Protection of liposomal lipids against radiation induced oxidative damage.

Liposomes were prepared from phospholipids extracted from biological membranes. A comparison was made between the peroxidation rate in handshake liposomes and in sonicated liposomes. The smaller sonicated liposomes were more vulnerable to peroxidation, probably because of the smaller radius of curvature, which results in a less dense packing of lipid molecules in the bilayer and a facilitated action of water radicals produced by the X-irradiation. High oxygen enhancement ratios were obtained, especially at low dose rates, suggesting the operation of slowly progressing chain reactions initiated by ionizing radiation. Three compounds were tested for their ability to protect the liposomal membranes against lipid peroxidation. The naturally occurring compounds reduced glutathione (GSH) and vitamin E(alpha-T) and the powerful radiation protector cysteamine (MEA). All three molecules could protect the liposomes against peroxidation. The membrane-soluble compound vitamin E was by far the most powerful. About 50 per cent protection was achieved by using 5 X 10(-6) M alpha-T, 10(-4) M GSH and 5 X 10(-4) M MEA. The fatty acid composition of the lipids altered drastically as a result of the irradiation. Arachidonic acid and docosahexanoic acid were the most vulnerable of the fatty acids. Very efficient protection of these polyunsaturated fatty acids could be obtained with relatively low concentrations of vitamin E built into the membranes.

Animals↗