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Water Research May 2022Mercury (Hg) and its compounds are a kind of worldwide concerned persistent toxic pollutants. As the major primary producer in the ocean, microalgae are expected to play...
Mercury (Hg) and its compounds are a kind of worldwide concerned persistent toxic pollutants. As the major primary producer in the ocean, microalgae are expected to play an important role in the cycling and accumulation of Hg in marine ecosystems by either uptake Hg species from seawater or involving in the transformations of Hg species. However, there is still lack of clear knowledge on whether microalgae can induce the methylation and demethylation of Hg in aquatic environments. In this study, Hg isotope dilution and isotope addition techniques were utilized to determine the methylation and demethylation potential of Hg at concentrations comparable to that in natural environments by 15 common marine microalgae (8 species of Diatoms, 4 species of Dinoflagellates, 2 species of Chlorophyta and 1 species of Chrysophyte). Methylation of inorganic Hg was found to be negligible in the culture of all tested marine microalgae, while 6 species could significantly induce the demethylation of methylmercury (MeHg). The rates of microalgae mediated MeHg demethylation were at the same order of magnitude as that of photodemethylation, indicating that marine microalgae may play an important role in the degradation of MeHg in marine environments. Further studies suggest that the demethylation of MeHg by the microalgae may be mainly caused by their extracellular secretions (via photo-induce demethylation) and associated bacteria, rather than the direct demethylation of MeHg by microalgae cells. In addition, it was found that thiol groups may be the major component in microalgal extracellular secretions that lead to the photo-demethylation of MeHg.
Topics: Demethylation; Ecosystem; Mercury; Methylation; Microalgae
PubMed: 35290869
DOI: 10.1016/j.watres.2022.118266 -
Environmental Science & Technology Jan 2024Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These...
Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These transformations have been reported to occur during human metabolism and wastewater treatment, leading to the propagation of CECs. When treated wastewater and biosolids are used in agriculture, CECs and their transformation products (TPs) are introduced into soil-plant systems. However, little is known about whether transformation cycles, such as methylation and demethylation, take place in higher plants and hence affect the fate of CECs in terrestrial ecosystems. In this study, we explored the interconversion between four common CECs (acetaminophen, diazepam, methylparaben, and naproxen) and their methylated or demethylated TPs in cells and whole wheat seedlings. The methylation-demethylation cycle occurred in both plant models with demethylation generally taking place at a greater degree than methylation. The transformation rate of demethylation or methylation was dependent on the bond strength of R-CH, with demethylation of methylparaben or methylation of acetaminophen being more pronounced. Although not explored in this study, these interconversions may exert influences on the behavior and biological activity of CECs, particularly in terrestrial ecosystems. The study findings demonstrated the prevalence of transformation cycles between CECs and their methylated or demethylated TPs in higher plants, contributing to a more complete understanding of risks of CECs in the human-wastewater-soil-plant continuum.
Topics: Humans; Wastewater; Water Pollutants, Chemical; Acetaminophen; Ecosystem; Soil; Methylation; Demethylation; Environmental Monitoring; Parabens
PubMed: 38240245
DOI: 10.1021/acs.est.3c03171 -
Journal of Agricultural and Food... Mar 20225-Demethylated polymethoxyflavones (5-OH PMFs) are the most unique monodemethylated PMFs with relatively low polarities and are proved to possess better anticancer and...
5-Demethylated polymethoxyflavones (5-OH PMFs) are the most unique monodemethylated PMFs with relatively low polarities and are proved to possess better anticancer and anti-inflammatory effects than their respective permethoxylated ones. However, their detailed metabolic fates have not been fully studied. 5-Demethylsinensetin (5-OH Sin), being one of the 5-demethylated citrus PMFs, was used in the present research to investigate its biotransformation in pharmacokinetics and excretion in rats. The results showed that 5-OH Sin was mostly accumulated in the large intestine, indicating its poor absorption in the small intestine. In addition, 5,3'-didemethylsinensetin and 5,4'-didemethylsinensetin were identified as two dominated metabolites of 5-OH Sin, and the C-3' position of 5-OH Sin was more facile to be demethylated in systemic circulation. Moreover, other than demethylation reactions, the methylation transformation of 5-OH Sin and its metabolites were also observed and quantified, suggesting that the bidirectional biotransformation between 5-OH Sin and its parent compound, Sin, occurred under conditions.
Topics: Animals; Biotransformation; Citrus; Demethylation; Flavones; Methylation; Rats
PubMed: 35230106
DOI: 10.1021/acs.jafc.1c07509 -
Cancer Research Apr 2019Since the identification of the first RNA demethylase and the establishment of methylated RNA immunoprecipitation-sequencing methodology 6 to 7 years ago, RNA... (Review)
Review
Since the identification of the first RNA demethylase and the establishment of methylated RNA immunoprecipitation-sequencing methodology 6 to 7 years ago, RNA methylation has emerged as a widespread phenomenon and a critical regulator of transcript expression. This new layer of regulation is termed "epitranscriptomics." The most prevalent RNA methylation, -methyladenosine (mA), occurs in approximately 25% of transcripts at the genome-wide level and is enriched around stop codons, in 5'- and 3'-untranslated regions, and within long internal exons. RNA mA modification regulates RNA splicing, translocation, stability, and translation into protein. mA is catalyzed by the RNA methyltransferases METTL3, METTL14, and METTL16 (writers), is removed by the demethylases FTO and ALKBH5 (erasers), and interacts with mA-binding proteins, such as YTHDF1 and IGF2BP1 (readers). RNA methyltransferases, demethylases, and mA-binding proteins are frequently upregulated in human cancer tissues from a variety of organ origins, increasing onco-transcript and oncoprotein expression, cancer cell proliferation, survival, tumor initiation, progression, and metastasis. Although RNA methyltransferase inhibitors are not available yet, FTO inhibitors have shown promising anticancer effects and in animal models of cancer. Further screening for selective and potent RNA methyltransferase, demethylase, or mA-binding protein inhibitors may lead to compounds suitable for future clinical trials in cancer patients.
Topics: Adenosine; Demethylation; Humans; Methylation; Methyltransferases; Neoplasms; RNA; RNA-Binding Proteins
PubMed: 30894375
DOI: 10.1158/0008-5472.CAN-18-2965 -
Science (New York, N.Y.) Dec 2022Active DNA demethylation maintains enhancer activity in nonproliferating cells but can damage DNA.
Active DNA demethylation maintains enhancer activity in nonproliferating cells but can damage DNA.
Topics: DNA Demethylation; Macrophages; Neurons; Enhancer Elements, Genetic; Humans; DNA Breaks, Single-Stranded
PubMed: 36454845
DOI: 10.1126/science.adf3171 -
Neuroendocrinology 2022Neurons expressing estrogen receptor (ER) ɑ in the arcuate (ARC) and ventromedial (VMH) nuclei of the hypothalamus sex-specifically control energy homeostasis, sexual...
INTRODUCTION
Neurons expressing estrogen receptor (ER) ɑ in the arcuate (ARC) and ventromedial (VMH) nuclei of the hypothalamus sex-specifically control energy homeostasis, sexual behavior, and bone density. Females have more ERɑ neurons in the VMH and ARC than males, and the sex difference in the VMH is eliminated by neonatal treatment with testosterone or a DNA methylation inhibitor.
OBJECTIVE
Here, we tested the roles of testosterone and DNA methylation/demethylation in development of ERɑ in the ARC.
METHODS
ERɑ was examined at birth and weaning in mice that received vehicle or testosterone subcutaneously, and vehicle or DNA methyltransferase inhibitor intracerebroventricularly, as neonates. To examine effects of DNA demethylation on the ERɑ cell number in the ARC, mice were treated neonatally with small interfering RNAs against ten-eleven translocase enzymes. The methylation status of the ERɑ gene (Esr1) was determined in the ARC and VMH using pyrosequencing of bisulfite-converted DNA.
RESULTS
A sex difference in ERɑ in the ARC, favoring females, developed between birth and weaning and was due to programming effects of testosterone. Neonatal inhibition of DNA methylation decreased ERɑ in the ARC of females, and an inhibition of
de methylation increased ERɑ in the ARC of males. The promoter region of Esr1 exhibited a small sex difference in percent of total methylation in the ARC (females > males) that was opposite to that in the VMH (males > females).CONCLUSION
DNA methylation and demethylation regulate ERɑ cell number in the ARC, and methylation correlates with activation of Esr1 in this region.
Topics: Animals; Arcuate Nucleus of Hypothalamus; DNA Methylation; Demethylation; Estrogen Receptor alpha; Female; Male; Mice; Sex Characteristics; Testosterone
PubMed: 34547753
DOI: 10.1159/000519671 -
Science Advances Jun 2020DNA demethylation is important for the erasure of DNA methylation. The role of DNA demethylation in plant development remains poorly understood. Here, we found extensive...
DNA demethylation is important for the erasure of DNA methylation. The role of DNA demethylation in plant development remains poorly understood. Here, we found extensive DNA demethylation in the CHH context around pericentromeric regions and DNA demethylation in the CG, CHG, and CHH contexts at discrete genomic regions during ectopic xylem tracheary element (TE) differentiation. While loss of pericentromeric methylation occurs passively, DNA demethylation at a subset of regions relies on active DNA demethylation initiated by DNA glycosylases ROS1, DML2, and DML3. The and mutations impair ectopic TE differentiation and xylem development in the young roots of seedlings. Active DNA demethylation targets and regulates many genes for TE differentiation. The defect of xylem development in is proposed to be caused by dysregulation of multiple genes. Our study identifies a role of active DNA demethylation in vascular development and reveals an epigenetic mechanism for TE differentiation.
Topics: Arabidopsis; Arabidopsis Proteins; DNA Demethylation; DNA Methylation; Gene Expression Regulation, Plant; Nuclear Proteins; Protein-Tyrosine Kinases; Proto-Oncogene Proteins
PubMed: 32637594
DOI: 10.1126/sciadv.aaz2963 -
Cells Feb 2019Lupus flares when genetically predisposed people encounter exogenous agents such as infections and sun exposure and drugs such as procainamide and hydralazine, but the... (Review)
Review
Lupus flares when genetically predisposed people encounter exogenous agents such as infections and sun exposure and drugs such as procainamide and hydralazine, but the mechanisms by which these agents trigger the flares has been unclear. Current evidence indicates that procainamide and hydralazine, as well as inflammation caused by the environmental agents, can cause overexpression of genes normally silenced by DNA methylation in CD4⁺ T cells, converting them into autoreactive, proinflammatory cytotoxic cells that are sufficient to cause lupus in mice, and similar cells are found in patients with active lupus. More recent studies demonstrate that these cells comprise a distinct CD4⁺ T cell subset, making it a therapeutic target for the treatment of lupus flares. Transcriptional analyses of this subset reveal proteins uniquely expressed by this subset, which may serve as therapeutic to deplete these cells, treating lupus flares.
Topics: Animals; DNA Methylation; Demethylation; Epigenesis, Genetic; Humans; Lupus Erythematosus, Systemic; T-Lymphocyte Subsets
PubMed: 30764520
DOI: 10.3390/cells8020127 -
Methods in Molecular Biology (Clifton,... 2022Here we describe how to profile the contribution of metabolism and implication of metals to histone methylation and demethylation. The techniques described with the...
Here we describe how to profile the contribution of metabolism and implication of metals to histone methylation and demethylation. The techniques described with the adequate protocols are metabolomics, quantitative proteomics, inductively coupled mass spectrometry and nanoscale secondary ion mass spectrometry.
Topics: Demethylation; Histones; Metals; Methylation; Spectrometry, Mass, Secondary Ion
PubMed: 35733013
DOI: 10.1007/978-1-0716-2481-4_6 -
Journal of Microbiological Methods Sep 2018The ability of enzymatic Kraft Lignin (KL) demethylation was determined using catechol and ferric ion coordination (catechol-Fe complexes) by reduction of Fe to Fe and...
The ability of enzymatic Kraft Lignin (KL) demethylation was determined using catechol and ferric ion coordination (catechol-Fe complexes) by reduction of Fe to Fe and formation of mono, bis- and/or tris-catechol-Fe complexes has been investigated to identify enzyme that can strip-off O-methyl groups from lignin such as O-demethylase. To detect fungal demethylation and release of catechol-like structures, these were demonstrated using catechol, gallic acid and caffeic acid as standard model compounds to forms mono, bis- and/or tris-catechol-Fe complexes. The catechol-Fe complexes formation controlled by pH via the deprotonation of the catechol hydroxyls was investigated at pH 2.5, 8.0 and 10.0 and demonstrated that catechol formed mono, bis- and/or tris-catechol-Fe complexes, and showed maximum absorbance at 547 nm. Lignin demethylation (O-demethylase) and formation of pyrocatecholic structures was detected using Aspergillus sp. and Galerina autumnalis culture filtrates as the enzyme source. The produced aromatic vicinal diol groups in lignin model compounds (LMCs) and KL were determined using different catecholic-binding reagents with the influence of HO along with 4-antiaminopyrine reagent, was analyzed by the following: i) Fe-catechol complexation method, ii) HNO method, iii) FAS (Ferric Ammonium-Sulfate) method, iv) Ti(III)-NTA (Titanium (III)- Nitrilotriacetate) method for hydrolytic zone formation. Among the tested methods showing lytic zone formation was Fe-catechol complexation. The LMCs and KL treated using Aspergillus sp. culture filtrate showed maximum Fe-catechol complexes with 3-methoxy catechol (91 μmol/mL), o-vanillin (44 μmol/mL) and KL (100 μmol/mL). In addition, Galerina autumnalis culture filtrate showed demethylation of vanillin (48 μmol/mL), 3-methoxy catechol (82 μmol/mL), o-vanillin, (33 μmol/mL), 3 4-dimethoxybenzyl alcohol (49 μmol/mL) and KL (41 μmol/mL). The results suggest that lignin demethylation (O-demethylases) activity that strip-off methyl groups in LMCs and KL and produced vicinal diols that covalently bind with Fe to form Fe-catechol complexes. The new Fe-catechol complexation method has the ability to characterize pyrocatechol and galloyl structures in chemically or biologically modified lignins and to detect O-demethylase activity.
Topics: Aspergillus; Basidiomycota; Benzaldehydes; Caffeic Acids; Catalysis; Catechols; Demethylation; Enzyme Assays; Ferric Compounds; Fungi; Gallic Acid; Hydrogen-Ion Concentration; Iron; Lignin; Oxidoreductases, O-Demethylating; Wood
PubMed: 30076868
DOI: 10.1016/j.mimet.2018.07.021