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1.
Nat Commun ; 15(1): 4061, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744897

ABSTRACT

Transcription stress has been linked to DNA damage -driven aging, yet the underlying mechanism remains unclear. Here, we demonstrate that Tcea1-/- cells, which harbor a TFIIS defect in transcription elongation, exhibit RNAPII stalling at oxidative DNA damage sites, impaired transcription, accumulation of R-loops, telomere uncapping, chromatin bridges, and genome instability, ultimately resulting in cellular senescence. We found that R-loops at telomeres causally contribute to the release of telomeric DNA fragments in the cytoplasm of Tcea1-/- cells and primary cells derived from naturally aged animals triggering a viral-like immune response. TFIIS-defective cells release extracellular vesicles laden with telomeric DNA fragments that target neighboring cells, which consequently undergo cellular senescence. Thus, transcription stress elicits paracrine signals leading to cellular senescence, promoting aging.


Subject(s)
Cellular Senescence , Cytosol , DNA Damage , Paracrine Communication , Telomere , Cellular Senescence/genetics , Animals , Telomere/metabolism , Telomere/genetics , Mice , Cytosol/metabolism , DNA/metabolism , Transcription, Genetic , Mice, Knockout , Humans , Extracellular Vesicles/metabolism , Genomic Instability , Aging/genetics , Aging/metabolism , Oxidative Stress , Mice, Inbred C57BL
2.
Environ Toxicol Pharmacol ; 98: 104064, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36640920

ABSTRACT

In the present study, the bidirectional interactions of Artemia franciscana with BPA, administered either alone or following treatment with the probiotics Bacillus subtilis, Lactococcus lactis or Lactobacillus plantarum, were evaluated. A 24 h exposure to BPA below LC50 induced oxidative stress to Artemia, indicated by diminished activity of superoxide dismutase, glutathione reductase, glutathione transferase and phenoloxidase, increased lipid peroxidation and decreased survival. Probiotic treatment prior to BPA exposure, led to increased survival, reduced lipid peroxidation and increased enzyme activities. BPA quantification in Artemia and its culture medium, showed a time dependent reduction in its levels, more evident in probiotic series, indicating its biotransformation. ESI-MS analysis confirmed the presence of the tentative BPA metabolites hydroquinone and BPA-sulfate, while BPA-disulfate formation was confirmed in only in the probiotic series. Our results provide evidence that probiotics alleviate the oxidative stress response induced by BPA, by enhancing the BPA biotransformation ability of Artemia.


Subject(s)
Artemia , Probiotics , Animals , Oxidative Stress , Phenols/pharmacology , Benzhydryl Compounds/pharmacology
3.
Methods Protoc ; 5(3)2022 May 01.
Article in English | MEDLINE | ID: mdl-35645346

ABSTRACT

Aquaculture, a mass supplier of seafood, relies on plastic materials that may contain the endocrine disruptors bisphenol-A (BPA) and tert-octylphenol (t-OCT). These pollutants present toxicity to Artemia, the live aquaculture feed, and are transferred through it to the larval stages of the cultured organisms. The purpose of this work is the development and validation of an analytical method to determine BPA and t-OCT in Artemia and their culture medium, using n-octylphenol as the internal standard. Extraction of the samples was performed with H2O/TFA (0.08%)-methanol (3:1), followed by SPE. Analysis was performed in a Nucleosil column with mobile phases A (95:5, v/v, 0.1% TFA in H2O:CH3CN) and B (5:95, v/v, 0.08% TFA in H2O:CH3CN). Calibration curves were constructed in the range of concentrations expected following a 24 h administration of BPA (10 µg/mL) or t-OCT (0.5 µg/mL), below their respective LC50. At the end of exposure to the pollutants, their total levels appeared reduced by about 32% for BPA and 35% for t-OCT, and this reduction could not be accounted for by photodegradation (9-19%). The developed method was validated in terms of linearity, accuracy, and precision, demonstrating the uptake of BPA and t-OCT in Artemia.

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