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Redox Biology Aug 2023Using S-phase synchronized RPE1-hTERT cells exposed to the DNA damaging agent, methyl methanesulfonate, we show the existence of a redox state associated with...
Using S-phase synchronized RPE1-hTERT cells exposed to the DNA damaging agent, methyl methanesulfonate, we show the existence of a redox state associated with replication stress-induced senescence termed senescence-associated redox state (SA-redox state). SA-redox state is characterized by its reactivity with superoxide-sensing fluorescent probes such as dihydroethidine, lucigenin and mitosox and peroxynitrite or hydroxyl radical sensing probe hydroxyphenyl fluorescein (HPF) but not the hydrogen peroxide (HO) reactive fluorescent probe CM-HDCFDA. Measurement of GSH and GSSH also reveals that SA-redox state mitigates the level of total GSH rather than oxidizes GSH to GSSG. Moreover, supporting the role of superoxide (O) in the SA-redox state, we show that incubation of senescent RPE1-hTERT cells with the O scavenger, Tiron, decreases the reactivity of SA-redox state with the oxidants' reactive probes lucigenin and HPF while the HO antioxidant N-acetyl cysteine has no effect. SA-redox state does not participate in the loss of proliferative capacity, G2/M cell cycle arrest or the increase in SA-β-Gal activity. However, SA-redox state is associated with the activation of NF-κB, dictates the profile of the Senescence Associated Secretory Phenotype, increases TFEB protein level, promotes geroconversion evidenced by increased phosphorylation of S6K and S6 proteins, and influences senescent cells response to senolysis. Furthermore, we provide evidence for crosstalk between SA redox state, p53 and p21. While p53 mitigates the establishment of SA-redox state, p21 is critical for the sustained reinforcement of the SA-redox state involved in geroconversion and resistance to senolysis.
Topics: Superoxides; Hydrogen Peroxide; Cellular Senescence; Tumor Suppressor Protein p53; Oxidation-Reduction
PubMed: 37285741
DOI: 10.1016/j.redox.2023.102757 -
Inorganic Chemistry May 2024One of the crucial metabolic processes for both plant and animal kingdoms is the oxidation of the amino acid tryptophan (TRP) that regulates plant growth and controls...
One of the crucial metabolic processes for both plant and animal kingdoms is the oxidation of the amino acid tryptophan (TRP) that regulates plant growth and controls hunger and sleeping patterns in animals. Here, we report revolutionary insights into how this process can be crucially affected by interactions with metal oxide nanoparticles (NPs), creating a toolbox for a plethora of important biomedical and agricultural applications. Molecular mechanisms in TRP-NP interactions were revealed by NMR and optical spectroscopy for ceria and titania and by X-ray single-crystal study and a computational study of model TRP-polyoxometalate complexes, which permitted the visualization of the oxidation mechanism at an atomic level. Nanozyme activity, involving concerted proton and electron transfer to the NP surface for oxides with a high oxidative potential, like CeO or WO, converted TRP in the first step into a tricyclic organic acid belonging to the family of natural plant hormones, auxins. TiO, a much poorer oxidant, was strongly binding TRP without concurrent oxidation in the dark but oxidized it nonspecifically via the release of reactive oxygen species (ROS) in daylight.
Topics: Cerium; Metal Nanoparticles; Models, Molecular; Oxidation-Reduction; Oxides; Titanium; Tryptophan
PubMed: 38684718
DOI: 10.1021/acs.inorgchem.3c03674 -
Environmental Health : a Global Access... Dec 2023Exhaled nitric oxide is a marker of airway inflammation. Air pollution induces airway inflammation and oxidative stress. Little is known about the impact of air... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Exhaled nitric oxide is a marker of airway inflammation. Air pollution induces airway inflammation and oxidative stress. Little is known about the impact of air pollution on exhaled nitric oxide in young infants.
METHODS
The Breathing for Life Trial recruited pregnant women with asthma into a randomised controlled trial comparing usual clinical care versus inflammometry-guided asthma management in pregnancy. Four hundred fifty-seven infants from the Breathing for Life Trial birth cohort were assessed at six weeks of age. Exhaled nitric oxide was measured in unsedated, sleeping infants. Its association with local mean 24-h and mean seven-day concentrations of ozone, nitric oxide, nitrogen dioxide, carbon monoxide, sulfur dioxide, ammonia, particulate matter less than 10 μm (PM10) and less than 2.5 μm (PM2.5) in diameter was investigated. The air pollutant data were sourced from local monitoring sites of the New South Wales Air Quality Monitoring Network. The association was assessed using a 'least absolute shrinkage and selection operator' (LASSO) approach, multivariable regression and Spearman's rank correlation.
RESULTS
A seasonal variation was evident with higher median exhaled nitric oxide levels (13.6 ppb) in warmer months and lower median exhaled nitric oxide levels (11.0 ppb) in cooler months, P = 0.008. LASSO identified positive associations for exhaled nitric oxide with 24-h mean ammonia, seven-day mean ammonia, seven-day mean PM10, seven-day mean PM2.5, and seven-day mean ozone; and negative associations for eNO with seven-day mean carbon monoxide, 24-h mean nitric oxide and 24-h mean sulfur dioxide, with an R-square of 0.25 for the penalized coefficients. These coefficients selected by LASSO (and confounders) were entered in multivariable regression. The achieved R-square was 0.27.
CONCLUSION
In this cohort of young infants of asthmatic mothers, exhaled nitric oxide showed seasonal variation and an association with local air pollution concentrations.
Topics: Female; Humans; Infant; Pregnancy; Air Pollutants; Air Pollution; Ammonia; Asthma; Carbon Monoxide; Inflammation; Nitric Oxide; Ozone; Particulate Matter; Sulfur Dioxide
PubMed: 38049853
DOI: 10.1186/s12940-023-01030-6 -
Frontiers in Immunology 2023Comparative animal models generate fundamental scientific knowledge of immune responses. However, these studies typically are conducted in mammals because of their... (Review)
Review
Comparative animal models generate fundamental scientific knowledge of immune responses. However, these studies typically are conducted in mammals because of their biochemical and physiological similarity to humans. Presently, there has been an interest in using teleost fish models to study intestinal immunology, particularly intestinal mucosa immune response. Instead of targeting the pathogen itself, a preferred approach for managing fish health is through nutrient supplementation, as it is noninvasive and less labor intensive than vaccine administrations while still modulating immune properties. Amino acids (AAs) regulate metabolic processes, oxidant-antioxidant balance, and physiological requirements to improve immune response. Thus, nutritionists can develop sustainable aquafeeds through AA supplementation to promote specific immune responses, including the intestinal mucosa immune system. We propose the use of dietary supplementation with functional AAs to improve immune response by discussing teleost fish immunology within the intestine and explore how oxidative burst is used as an immune defense mechanism. We evaluate immune components and immune responses in the intestine that use oxidant-antioxidant balance through potential selection of AAs and their metabolites to improve mucosal immune capacity and gut integrity. AAs are effective modulators of teleost gut immunity through oxidant-antioxidant balance. To incorporate nutrition as an immunoregulatory means in teleost, we must obtain more tools including genomic, proteomic, nutrition, immunology, and macrobiotic and metabonomic analyses, so that future studies can provide a more holistic understanding of the mucosal immune system in fish.
Topics: Animals; Humans; Antioxidants; Immunonutrition Diet; Oxidants; Immunity, Mucosal; Amino Acids; Proteomics; Fishes; Intestinal Mucosa; Mammals
PubMed: 37841275
DOI: 10.3389/fimmu.2023.1241615 -
Redox Biology Apr 2024Endothelial dysfunction and endothelial activation are common early events in vascular diseases and can arise from mitochondrial dysfunction. Neurogranin (Ng) is a 17kD...
Endothelial dysfunction and endothelial activation are common early events in vascular diseases and can arise from mitochondrial dysfunction. Neurogranin (Ng) is a 17kD protein well known to regulate intracellular Ca-calmodulin (CaM) complex signaling, and its dysfunction is significantly implicated in brain aging and neurodegenerative diseases. We found that Ng is also expressed in human aortic endothelial cells (HAECs), and depleting Ng promotes Ca-CaM complex-dependent endothelial activation and redox imbalances. Endothelial-specific Ng knockout (Cre-CDH5-Ng) mice demonstrate a significant delay in the flow-mediated dilation (FMD) response. Therefore, it is critical to characterize how endothelial Ng expression regulates reactive oxygen species (ROS) generation and affects cardiovascular disease. Label-free quantification proteomics identified that mitochondrial dysfunction and the oxidative phosphorylation pathway are significantly changed in the aorta of Cre-CDH5-Ng mice. We found that a significant amount of Ng is expressed in the mitochondrial fraction of HAECs using western blotting and colocalized with the mitochondrial marker, COX IV, using immunofluorescence staining. Seahorse assay demonstrated that a lack of Ng decreases mitochondrial respiration. Treatment with MitoEbselen significantly restores the oxygen consumption rate in Ng knockdown cells. With the RoGFP-Orp1 approach, we identified that Ng knockdown increases mitochondrial-specific hydrogen peroxide (HO) production, and MitoEbselen treatment significantly reduced mitochondrial ROS (mtROS) levels in Ng knockdown cells. These results suggest that Ng plays a significant role in mtROS production. We discovered that MitoEbselen treatment also rescues decreased eNOS expression and nitric oxide (NO) levels in Ng knockdown cells, which implicates the critical role of Ng in mtROS-NO balance in the endothelial cells.
Topics: Animals; Humans; Mice; Endothelial Cells; Hydrogen Peroxide; Mitochondria; Mitochondrial Diseases; Neurogranin; Nitric Oxide; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 38359746
DOI: 10.1016/j.redox.2024.103085 -
International Journal of Molecular... Aug 2023The spermatozoa have limited antioxidant defences, a high polyunsaturated fatty acids content and the impossibility of synthesizing proteins, thus being susceptible to...
The spermatozoa have limited antioxidant defences, a high polyunsaturated fatty acids content and the impossibility of synthesizing proteins, thus being susceptible to oxidative stress. High levels of reactive oxygen species (ROS) harm human spermatozoa, promoting oxidative damage to sperm lipids, proteins and DNA, leading to infertility. Coenzyme A (CoA) is a key metabolic integrator in all living cells. Recently, CoA was shown to function as a major cellular antioxidant mediated by a covalent modification of surface-exposed cysteines by CoA (protein CoAlation) under oxidative or metabolic stresses. Here, the profile of protein CoAlation was examined in sperm capacitation and in human spermatozoa treated with different oxidizing agents (hydrogen peroxide, (HO), diamide and tert-butyl hydroperoxide (t-BHP). Sperm viability and motility were also investigated. We found that HO and diamide produced the highest levels of protein CoAlation and the greatest reduction of sperm motility without impairing viability. Protein CoAlation levels are regulated by 2-Cys peroxiredoxins (PRDXs). Capacitated spermatozoa showed lower levels of protein CoAlation than non-capacitation cells. This study is the first to demonstrate that PRDXs regulate protein CoAlation, which is part of the antioxidant response of human spermatozoa and participates in the redox regulation associated with sperm capacitation.
Topics: Humans; Male; Hydrogen Peroxide; Antioxidants; Diamide; Sperm Motility; Semen; Oxidative Stress; Reactive Oxygen Species; Spermatozoa; Peroxiredoxins
PubMed: 37569900
DOI: 10.3390/ijms241512526 -
Ecotoxicology and Environmental Safety Sep 2023Studtite and meta-studtite are the only two uranyl peroxides found in nature. Sparsely soluble studtite has been found in natural uranium deposits, on the surface of...
Studtite and meta-studtite are the only two uranyl peroxides found in nature. Sparsely soluble studtite has been found in natural uranium deposits, on the surface of spent nuclear fuel in contact with water and on core material from major nuclear accidents such as Chernobyl. The formation of studtite on the surface of nuclear fuel can have an impact on the release of radionuclides to the biosphere. In this work, we have experimentally studied the formation of studtite as function of HCO concentration and pH. The results show that studtite can form at pH ≤ 10 in solutions without added HCO. At pH ≤ 7, the precipitate was found to be mainly studtite, while at 8 ≤ pH ≤ 9.8, a mixture of studtite and meta-schoepite was found. Studtite formation from UO and HO was observed at [HCO] ≤ 2 mM and studtite was only found to dissolve at [HCO] > 2 mM.
Topics: Bicarbonates; Hydrogen Peroxide; Uranium Compounds; Peroxides; Water
PubMed: 37494736
DOI: 10.1016/j.ecoenv.2023.115297 -
Redox Biology May 2024We obviously agree with Wu et al. that HO might accumulate in the Archean land waters devoid of Fe. We do disagree on the topic of the half-life of HO, as the work cited...
We obviously agree with Wu et al. that HO might accumulate in the Archean land waters devoid of Fe. We do disagree on the topic of the half-life of HO, as the work cited in support for a longer half-live is not relevant to the conditions in the Archean ocean. While the existence of radicals in quartz is not in doubt, we do question the hypothesis that these radicals oxidize water to HO and HO.
Topics: Hydrogen Peroxide; Oxygen; Photosynthesis; Hydroxyl Radical; Oxidation-Reduction
PubMed: 38492556
DOI: 10.1016/j.redox.2024.103110 -
Journal of Dentistry Oct 2023Denture stomatitis is prevalent in older people and poses serious health risks. Ready-to-use (RTU) neutral-pH Electrolysed Oxidizing Water (EOW) is an effective...
OBJECTIVES
Denture stomatitis is prevalent in older people and poses serious health risks. Ready-to-use (RTU) neutral-pH Electrolysed Oxidizing Water (EOW) is an effective environmental disinfectant used in residential care settings and geriatric wards. However, the influence of storage on stability and effectiveness for denture disinfection has not been established. This research investigated the storage-related stability and antimicrobial activity of RTU EOW, and its efficacy against Candida albicans biofilms formed on denture resin.
METHODS
The pH, oxidation/reduction potential (mV), available chlorine content (mg/L) and [HOCl] (mM) of RTU EOW (Envirolyte, New Zealand) solutions (n = 22) were measured from bottle opening to 28 days following storage at 4 °C, room temperature (RT) or 37 °C. Staphylococcus aureus and C. albicans cells were incubated in 80% EOW for contact times (CTs) up to 15 min and colony-forming units (cfu) determined. Minimum inhibitory concentrations (MIC EOW-HOCl) after CTs up to five minutes were determined for S. aureus and C. albicans reference strains and clinical isolates. C. albicans-denture resin disc biofilms were assessed after a five-minute CT with undiluted EOW by XTT-metabolic activity assay.
RESULTS
[HOCl] remained stable when RTU EOW was stored at 4 °C or RT for five months after manufacture. One-minute CT resulted in log cfu reductions of >6 for S. aureus and >5 for C. albicans. Mean MIC for five-minute CT was 37 µM (S. aureus) and 54 µM (C. albicans). Undiluted EOW reduced C. albicans biofilm metabolic activity by 86%.
CONCLUSIONS
RTU neutral-pH EOW is stable over five-months storage and is an effective denture disinfectant.
CLINICAL SIGNIFICANCE
The efficacy of the RTU neutral EOW against C. albicans isolates and biofilms formed on denture resin surfaces supports its use as a denture disinfectant and can inform future research to assess its potential for preventing denture-related oral Candida infections in the older population, especially in resource-limited communities.
Topics: Humans; Aged; Water; Staphylococcus aureus; Candida albicans; Disinfectants; Biofilms; Hydrogen-Ion Concentration; Denture Bases
PubMed: 37567495
DOI: 10.1016/j.jdent.2023.104656 -
International Journal of Molecular... Sep 2023It has been reported that in an oxidative environment, the flavonoid ,-dihydroquercetin (,-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin...
It has been reported that in an oxidative environment, the flavonoid ,-dihydroquercetin (,-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than ,-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that ,-DHQ is oxidized by horseradish peroxidase (HRP), with HO as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a ,-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the ,-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to ,-DHQ. No ,-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of ,-DHQ quinone to ,-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of ,-DHQ is observed, and that GSH adducts the oxidized product of ,-DHQ on the B-ring, led us to conclude that the redox-modulating activity of ,-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of ,-DHQ in an oxidative environment does not result in 'biotargeting' quercetin.
Topics: Antioxidants; Quercetin; Hydrogen Peroxide; Ascorbic Acid; Glutathione; Quinones
PubMed: 37762525
DOI: 10.3390/ijms241814220