Importance of methyl donors during reproduction.
Ontology highlight
ABSTRACT:
SUBMITTER: Zeisel SH
PROVIDER: S-EPMC2628952 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Diet changes can partly explain the high burden of asthma in industrialised nations. Findings from experimental studies have stimulated many observational studies of the association between vitamins (A, C, D, and E) or nutrients acting as methyl donors (folate, vitamin B12, and choline) and asthma. However, observational studies are susceptible to several sources of bias; well conducted randomised controlled trials (RCTs) are the gold standard to establish whether diet has an effect on asthma. Evidence from observational studies and a few RCTs strongly justifies ongoing and future RCTs in three areas: vitamin D for the prevention or treatment of asthma, choline supplementation as adjuvant treatment for asthma, and vitamin E to prevent the detrimental effects of air pollution in patients with asthma. At present, insufficient evidence exists to recommend supplementation with any vitamin or nutrient acting as a methyl donor to prevent or treat asthma.
| S-EPMC3904132 | biostudies-literature
Project description:Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of life could program brain development and have long-lasting effects on mental health. Studies have shown that early nutritional intervention that includes methyl-donors improves cognitive functions throughout life. Choline is a micronutrient and a methyl donor that is required for normal brain growth and development. It plays a pivotal role in maintaining structural and functional integrity of cellular membranes. It also regulates cholinergic signaling in the brain via the synthesis of acetylcholine. Via its metabolites, it participates in pathways that regulate methylation of genes related to memory and cognitive functions at different stages of development. Choline-related functions have been dysregulated in some neurodegenerative diseases suggesting choline role in influencing mental health across the lifespan.
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Project description:Anthranilic acids were recently reported as superior catalysts for hydrazone and oxime formation compared to aniline, the classic catalyst for these reactions. Here, alternative proton donors were examined with varied pKa in an effort to enhance activity at biological pH. The experiments show that 2-aminobenzenephosphonic acids are superior to anthranilic acids in catalyzing hydrazone formation with common aldehyde substrates.
| S-EPMC3618716 | biostudies-literature
Project description:The present investigation theoretically reports the comprehensive kinetic mechanism of the reaction between aniline and the methyl radical over a wide range of temperatures (300-2000 K) and pressures (76-76,000 Torr). The potential energy surface of the C6H5NH2 + CH3 reaction has been established at the CCSD(T)//M06-2X/6-311++G(3df,2p) level of theory. The conventional transition-state theory (TST) was utilized to calculate rate constants for the elementary reaction channels, while the stochastic RRKM-based master equation framework was applied for the T- and P-dependent rate-coefficient calculation of multiwell reaction paths. Hindered internal rotation and Eckart tunneling treatments were included. The H-abstraction from the -NH2 group of aniline (to form P1 (C6H5NH + CH4)) has been found to compete with the CH3-addition on the C atom at the ortho site of aniline (to form IS2) with the atmospheric rate expressions (in cm3 molecule-1 s-1) as ka1 = 7.5 × 10-23 T3.04 exp[(-40.63 ± 0.29 kJ·mol-1)/RT] and kb2 = 2.29 × 10-3 T-3.19 exp[(-56.94 ± 1.17 kJ·mol-1)/RT] for T = 300-2000 K and P = 760 Torr. Even though rate constants of several reaction channels decrease with increasing pressures, the total rate constant ktotal = 7.71 × 10-17 T1.20 exp[(-40.96 ± 2.18 kJ·mol-1)/RT] of the title reaction still increases as the pressure increases in the range of 76-76,000 Torr. The calculated enthalpy changes for some species are in good agreement with the available experimental data within their uncertainties (the maximum deviation between theory and experiment is ∼11 kJ·mol-1). The T1 diagnostic and spin contamination analysis for all species involved have also been observed. This work provides sound quality rate coefficients for the title reaction, which will be valuable for the development of detailed combustion reaction mechanisms for hydrocarbon fuels.
| S-EPMC10193547 | biostudies-literature
Project description:The aim of this study was to evaluate the potential effects of methyl donor supplementation of pregnant animals in the presence or absence of a concomitant lactation on the methylome of the offspring. Twenty Holstein cows, 10 nulliparous (non-lactating while pregnant) and 10 multiparous (lactating while pregnant) were blocked by parity and randomly assigned to an i.m. weekly injections of a placebo (CTRL) or a solution containing methyl donors (MET). After calving, 5 calves randomly selected from each treatment (two born to non-lactating and three to lactating dams) were blood-sampled to determine their full methylome. There were more than 2,000 CpG differentially methylated between calves born to CTRL and those born to MET, and also between calves born to lactating and non-lactating dams. Most of the differences affected genes involved in immune function, cell growth regulation and differentiation, kinase activity, and ion channeling. We conclude that the coexistence of pregnancy and lactation affects the methylome of the offspring, and that supplementation of methyl donors early in gestation has also consequences on the methylome.
| S-EPMC5724855 | biostudies-literature
Project description:It has been proposed that in slow-growing vertebrate populations survival generally has a greater influence on population growth than reproduction. Despite many studies cautioning against such generalizations for conservation, wildlife management for slow-growing populations still often focuses on perturbing survival without careful evaluation as to whether those changes are likely or feasible. Here, we evaluate the relative importance of reproduction and survival for the conservation of two bottlenose dolphin (Tursiops cf aduncus) populations: a large, apparently stable population and a smaller one that is forecast to decline. We also assessed the feasibility and effectiveness of wildlife management objectives aimed at boosting either reproduction or survival. Consistent with other analytically based elasticity studies, survival had the greatest effect on population trajectories when altering vital rates by equal proportions. However, the findings of our alternative analytical approaches are in stark contrast to commonly used proportional sensitivity analyses and suggest that reproduction is considerably more important. We show that in the stable population reproductive output is higher, and adult survival is lower;the difference in viability between the two populations is due to the difference in reproduction;reproductive rates are variable, whereas survival rates are relatively constant over time;perturbations on the basis of observed, temporal variation indicate that population dynamics are much more influenced by reproduction than by adult survival;for the apparently declining population, raising reproductive rates would be an effective and feasible tool to reverse the forecast population decline; increasing survival would be ineffective. Our findings highlight the importance of reproduction - even in slow-growing populations - and the need to assess the effect of natural variation in vital rates on population viability. We echo others in cautioning against generalizations based on life-history traits and recommend that population modeling for conservation should also take into account the magnitude of vital rate changes that could be attained under alternative management scenarios.
| S-EPMC5513288 | biostudies-literature
Project description:Background and purposeDNA hypomethylation was previously implicated in metastasis. In the present study, we examined whether methyl supplementation with the universal methyl donor S-adenosylmethionine (SAM) inhibits prostate cancer associated skeletal metastasis.Experimental approachHighly invasive human prostate cancer cells PC-3 and DU-145 were treated with vehicle alone, S-adenosylhomocysteine (SAH) or SAM and their effects on tumour cell proliferation, invasion, migration and colony formation were monitored. For in vivo studies, control (SAH) and SAM-treated PC-3 cells were injected into the tibia of Fox chase SCID mice and skeletal lesions were determined by X-ray and μCT. To understand possible mechanisms involved, we delineated the effect of SAM on the genome-wide methylation profile of PC-3 cells.Key resultsTreatment with SAM resulted in a dose-dependent inhibition of tumour cell proliferation, invasion, cell migration, colony formation and cell cycle characteristics. Animals injected with 250 μM SAM-treated cells developed significantly smaller skeletal lesions, which were associated with increases in bone volume to tumour volume ratio and connectivity density as well as decreased trabecular spacing. Genome-wide methylation analysis showed differential methylation in several key signalling pathways implicated in prostate cancer including the signal transducer and activator of transcription 3 (STAT3) pathway. A selective STAT3 inhibitor decreased tumour cell invasion, effects which were less pronounced as compared with SAM.Conclusions and implicationsThese studies provide a possible mechanism for the role of DNA demethylation in the development of skeletal metastasis and a rationale for the use of hypermethylation pharmacological agents to impede the development and progression of skeletal metastasis.
| S-EPMC4439874 | biostudies-literature
Project description:Asthma is a complex heritable disease that is increasing in prevalence and severity, particularly in developed countries such as the United States, where 11% of the population is affected. The contribution of environmental and genetic factors to this growing epidemic is currently not well understood. We developed the hypothesis, based on previous literature, that changes in DNA methylation resulting in aberrant gene transcription may enhance the risk of developing allergic airway disease. Our findings indicate that in mice, a maternal diet supplemented with methyl donors enhanced the severity of allergic airway disease that was inherited transgenerationally. Using a genomic approach, we discovered 82 gene-associated loci that were differentially methylated after in utero supplementation with a methyl-rich diet. These methylation changes were associated with decreased transcriptional activity and increased disease severity. Runt-related transcription factor 3 (Runx3), a gene known to negatively regulate allergic airway disease, was found to be excessively methylated, and Runx3 mRNA and protein levels were suppressed in progeny exposed in utero to a high-methylation diet. Moreover, treatment with a demethylating agent increased Runx3 gene transcription, further supporting our claim that a methyl-rich diet can affect methylation status and consequent transcriptional regulation. Our findings indicate that dietary factors can modify the heritable risk of allergic airway disease through epigenetic mechanisms during a vulnerable period of fetal development in mice.
| S-EPMC2542847 | biostudies-literature
Project description:Bacteria use quorum sensing to probe and respond to population densities in their external environment. The detection of quorum signaling molecules causes a virulence response in many pathogenic bacteria. Blocking this signaling pathway, without interfering with critical metabolic functions, would produce compounds that can disarm pathogens without killing them. By not blocking growth per se, this therapeutic approach would have a lower associated risk for the development of bacterial resistance. Modified forms of l-methionine can yield analogues of the essential methyl donor, S-adenosyl-l-methionine (AdoMet), by serving as substrates for AdoMet synthetase [Zano, S., et al. (2013) Arch. Biochem. Biophys. 536, 64]. The AdoMet analogues examined here were chosen for their putative inability to serve as precursors for the synthesis of the acylhomoserine lactone class of quorum sensing molecules. We now show that these AdoMet analogues can still function as methyl donors, for methylation of both DNA and catechol-based neurotransmitters. The rates of methyl transfer for several of these altered AdoMet analogues are comparable to those observed with unmodified AdoMet. Additional refinement of these structures is expected to produce lead compounds to be tested as selective therapeutic agents against infections by a broad range of pathogenic Gram-negative bacteria.
| S-EPMC3985469 | biostudies-other
Project description:Atherosclerosis is an inflammatory condition of the arterial wall mediated by cells of both innate and adaptive immunity. T lymphocytes play an important role in orchestrating the pathogenic immune response involved in the acceleration of atherosclerosis. Previously, we have shown that a prenatal methyl-donor supplementation diet (MS), when fed to dams during pregnancy and lactation, decreased the T cell-mediated pro-inflammatory cytokine and chemokine response in F1 mice. In the current study, we report feeding Apolipoprotein E (ApoE(-/-)) deficient dams with the MS diet during pregnancy reduces atherosclerotic plaques in F1 mice that were fed high fat diet (HFD) after weaning. F1 mice from dams on the MS diet exhibited increased global T cell DNA methylation. T-cell chemokines and their receptors (in particular CCR2, CCR5, and CXCR3) play important roles in the inflammatory cell recruitment to vascular lesions. MS diet significantly reduced Ccr2 mRNA and protein expression in CD3+ T cells but not in CD11b+ monocytes in MS F1 mice relative to controls. F1 litter size, HFD consumption, body weight, and body fat were similar between control and MS diet groups. Moreover, serum thiol metabolite levels were similar between the two groups. However, MS diet is associated with significantly higher serum HDL and lower LDL+VLDL levels in comparison to F1 mice from dams on the control diet. Inflammatory cytokines (IL-17, TNF-α, IL-6) were also lower in MS F1 mice serum and conditioned media from T-cell culture. Altogether, these data suggest that the MS diet ameliorates development of atherosclerosis by inhibiting the T-cell Ccr2 expression, reducing inflammatory cytokines production and increasing serum HDL:LDL ratio.
| S-EPMC3578836 | biostudies-literature