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Hussain Mohamad Awwad, Carsten-Henning Ohlmann, Michael Stoeckle, Juergen Geisel, Rima Obeid
BACKGROUND: Folate is required for synthesis of methyl groups and DNA in growing cells. The association between folate and prostate cancer (PCa) is not conclusive. METHODS: We investigated concentrations of folate vitamers, S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) in blood of men with PCa (n = 129) or benign prostatic hyperplasia (BPH) (n = 73) who were recruited just after the first diagnosis. RESULTS: In younger subjects <65 years, concentrations of (6S)-5-CH3 -H4 folate (15...
April 16, 2018: Clinical Biochemistry
Judy R Rees, Carolyn B Morris, Janet L Peacock, Per M Ueland, Elizabeth L Barry, Gail E McKeown-Eyssen, Jane C Figueiredo, Dale C Snover, John A Baron
In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence...
August 2017: Cancer Prevention Research
Mehala Subramaniapillai, Nicole E Carmona, Carola Rong, Roger S McIntyre
Mood disorders continue to be a significant burden to those affected, resulting in significant illness-associated disability and premature mortality. In addition to mood disturbance, individuals also suffer from other transdiagnostic impairments (eg, anhedonia and cognitive impairment). Although there have been significant advancements in psychiatric treatment over the last few decades, treatment efficacy (eg, symptom remission, lack of functional recovery, and disease modification) continues to be an important limitation...
March 2017: Dialogues in Clinical Neuroscience
Rachelle E Irwin, Kristina Pentieva, Tony Cassidy, Diane J Lees-Murdock, Marian McLaughlin, Girijesh Prasad, Helene McNulty, Colum P Walsh
DNA methylation provides an attractive possible means for propagating the effects of environmental inputs during fetal life and impacting subsequent adult mental health, which is leading to increasing collaboration between molecular biologists, nutritionists and psychiatrists. An area of interest is the potential role of folate, not just in neural tube closure in early pregnancy, but in later major neurodevelopmental events, with consequences for later sociocognitive maturation. Here, we set the scene for recent discoveries by reviewing the major events of neural development during fetal life, with an emphasis on tissues and structures where dynamic methylation changes are known to occur...
June 2016: Epigenomics
Naila Naz, Alicia Requena Jimenez, Anna Sanjuan-Vilaplana, Megan Gurney, Jaleel Miyan
Folate is vital in a range of biological processes and folate deficiency is associated with neurodevelopmental disorders such as neural tube defects and hydrocephalus (HC). 10-formyl-tetrahydrofolate-dehydrogenase (FDH) is a key regulator for folate availability and metabolic interconversion for the supply of 1-carbon groups. In previous studies, we found a deficiency of FDH in CSF associated with the developmental deficit in congenital and neonatal HC. In this study, we therefore aimed to investigate the role of FDH in folate transport and metabolism during the brain development of the congenital hydrocephalic Texas (H-Tx) rat and normal (Sprague-Dawley) rats...
August 2016: Journal of Neurochemistry
Pankaj Bhatia, Nirmal Singh
Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re-methylated to methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 5-methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CβS), and cystathionine-γ-lyase (CγL) or deficiency in cofactors (vitamin B6 , B12 , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia...
December 2015: Fundamental & Clinical Pharmacology
Megan M Niedzwiecki, Xinhua Liu, Megan N Hall, Tiffany Thomas, Vesna Slavkovich, Vesna Ilievski, Diane Levy, Shafiul Alam, Abu B Siddique, Faruque Parvez, Joseph H Graziano, Mary V Gamble
BACKGROUND: Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)-a class I human carcinogen linked to skin lesion and cancer risk-is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied. METHODS: We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19-66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30-63 years)...
November 2015: Cancer Epidemiology, Biomarkers & Prevention
Mansi Dass Singh, Philip Thomas, Julie Owens, William Hague, Michael Fenech
Dietary deficiencies of folate and other B vitamin cofactors involved in one-carbon metabolism, together with genetic polymorphisms in key folate-methionine metabolic pathway enzymes, are associated with increases in circulating plasma homocysteine, reduction in DNA methylation patterns, and genome instability events. All of these biomarkers have also been associated with pre-eclampsia. The aim of this review was to explore the literature and identify potential knowledge gaps in relation to the role of folate at the genomic level in either the etiology or the prevention of pre-eclampsia...
October 2015: Nutrition Reviews
Anne Rochtus, Katrien Jansen, Chris Van Geet, Kathleen Freson
Neural tube defects (NTDs), affecting 1-2 per 1000 pregnancies, are severe congenital malformations that arise from the failure of neurulation during early embryonic development. The methylation hypothesis suggests that folate prevents NTDs by stimulating cellular methylation reactions. Folate is central to the one-carbon metabolism that produces pyrimidines and purines for DNA synthesis and for the generation of the methyldonor S-adenosyl-methionine. This review focuses on the relation between the folate-mediated one-carbon metabolism, DNA methylation and NTDs...
2015: Mini Reviews in Medicinal Chemistry
M D Araújo, B N Borges, S Rodrigues-Antunes, R M R Burbano, M L Harada
The folate metabolic pathway, which is involved in DNA synthesis and methylation, is associated with individual susceptibility to several diseases, including gastric tumors. In this study, we investigated four polymorphisms [thymidylate synthase enhancer region, single nucleotide polymorphism thymidylate synthase 5' (TS5'), TS3' untranslated region, and methylenetetrahydrofolate reductase (MTHFR) 677C> T] in 2 genes related to the folate pathway, TS and MTHFR, and their possible association with the risk gastric cancer development in a population from Pará state, Brazil...
2015: Genetics and Molecular Research: GMR
Mahmoud Aarabi, Maria C San Gabriel, Donovan Chan, Nathalie A Behan, Maxime Caron, Tomi Pastinen, Guillaume Bourque, Amanda J MacFarlane, Armand Zini, Jacquetta Trasler
Dietary folate is a major source of methyl groups required for DNA methylation, an epigenetic modification that is actively maintained and remodeled during spermatogenesis. While high-dose folic acid supplementation (up to 10 times the daily recommended dose) has been shown to improve sperm parameters in infertile men, the effects of supplementation on the sperm epigenome are unknown. To assess the impact of 6 months of high-dose folic acid supplementation on the sperm epigenome, we studied 30 men with idiopathic infertility...
November 15, 2015: Human Molecular Genetics
Irene Pusceddu, Markus Herrmann, Susanne H Kirsch, Christian Werner, Ulrich Hübner, Marion Bodis, Ulrich Laufs, Stefan Wagenpfeil, Jürgen Geisel, Wolfgang Herrmann
PURPOSE: Deficiencies of folate, vitamins B12 and D are common age-related conditions. Vitamin B12 and folate are necessary for DNA methylation. Telomeres appear to be regulated by DNA methylation. Here, we study the effect of B vitamins supplementation on telomere length and global DNA methylation in a prospective study. METHODS: In total, 60 elderly subjects were supplemented for 1 year with either vitamin B12, B6, folate, vitamin D and calcium (group A n = 31) or only vitamin D and calcium (group B n = 29)...
August 2016: European Journal of Nutrition
Shuyu Zhang, Changhe Shi, Chengyuan Mao, Bo Song, Haiman Hou, Jun Wu, Xinjing Liu, Haiyang Luo, Shilei Sun, Yuming Xu
BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease, and its pathological hallmark is the accumulation of α-synuclein proteins. Homocysteine (Hcy) is an intermediate amino acid generated during the metabolism of methionine. Hcy may contribute to the pathogenesis of neurodegenerative disorders. Vitamin B12 and folate are cofactors necessary for the methylation of homocysteine. METHODS: This study compared the levels of serum Hcy, vitamin B12 and folate in patients with MSA with those in healthy people to reveal the possible association between MSA and plasma levels of Hcy, vitamin B12 and folate...
2015: PloS One
Martin Wagner, Sungwoo Choi, Katrin Panzitt, Jennifer L Mamrosh, Jae Man Lee, Alex Zaufel, Rui Xiao, Ruth Wooton-Kee, Marcus Ståhlman, Christopher B Newgard, Jan Borén, David D Moore
UNLABELLED: Balance of labile methyl groups (choline, methionine, betaine, and folate) is important for normal liver function. Quantitatively, a significant use of labile methyl groups is in the production of phosphatidylcholines (PCs), which are ligands for the nuclear liver receptor homolog-1 (LRH-1). We studied the role of LRH-1 in methyl-pool homeostasis and determined its metabolic effects using the methionine and choline-deficient (MCD) diet, which depletes methyl groups and results in a deleterious decrease in the PC-to-phosphatidylethanolamine ratio...
January 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Yanqing Geng, Rufei Gao, Xuemei Chen, Xueqing Liu, Xinggui Liao, Yanli Li, Shangjing Liu, Yubin Ding, Yingxiong Wang, Junlin He
Existing evidence suggests that adverse pregnancy outcomes are closely related with dietary factors. Previous studies in mice have focused on the harm of folate deficiency (FD) on development of embryo, while the effect of low maternal folate levels on maternal intrauterine environment during early pregnancy remains unclear. Since our previous study found that FD treatment of mice causes no apparent defects in embryo implantation but is accompanied by female subfertility, we next chose to investigate a potential role of FD on molecular events after implantation...
November 2015: Molecular Human Reproduction
Bernard D Lemire
FOXRED1 mutations result in complex I (NADH:ubiquinone oxidoreductase) deficiencies and Leigh syndrome (subacute necrotizing encephalomyelopathy). FOXRED1 is a mitochondrial flavoprotein related to N-methyl amino acid dehydrogenases. How is FOXRED1 required for the biogenesis of complex I? I present a hypothesis that suggests FOXRED1 catalytic activity as a sarcosine oxidase protects the developing fetus from oxidative stress during pregnancy. Loss of FOXRED1, coupled with protein, choline and/or folate-deficient diets results in the depletion of glutathione, the dysregulation of nitric oxide metabolism and the peroxynitrite-mediated inactivation of complex I...
September 2015: Mitochondrion
Huan Liu, Wen Li, Shijing Zhao, Xumei Zhang, Meilin Zhang, Yanyu Xiao, John X Wilson, Guowei Huang
PURPOSE: Alzheimer's disease (AD) is a highly prevalent type of dementia. The epigenetic mechanism of gene methylation provides a putative link between nutrition, one-carbon metabolism, and disease progression because folate deficiency may cause hypomethylation of promoter regions in AD-relevant genes. We hypothesized that folic acid supplementation may protect neuron cells from amyloid β (Aβ) oligomer-induced toxicity by modulating DNA methylation of APP and PS1 in AD models. METHODS: Primary hippocampal neuronal cells and hippocampal HT-22 cells were incubated for 24 h with a combination of folic acid and either Aβ oligomers or vehicle and were then incubated for 72 h with various concentrations of folic acid...
August 2016: European Journal of Nutrition
Sydella A Blatch, Sally P Stabler, Jon F Harrison
Mechanisms of vitamin function in non-mammals are poorly understood, despite being essential for development. Folate and cobalamin are B-vitamin cofactors with overlapping roles in transferring various single-carbon units. In mammals, one or both is needed for nucleotide synthesis, DNA methylation, amino acid conversions and other reactions. However, there has been little investigation of the response to folate or cobalamin in insects. Here, we manipulated folate intake and potentially cobalamin levels in the fruit fly Drosophila melanogaster with chemically-defined diets, an antibiotic to reduce bacterially-derived vitamins, and the folate-interfering pharmaceutical methotrexate, to see if single-carbon metabolites and DNA synthesis rates would be affected...
November 2015: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Matthew P Hanley, Daniel W Rosenberg
For many years folic acid has been evaluated for its utility as a chemopreventive agent due to its position at the center of the one-carbon metabolic network. This network is responsible for generating precursors to nucleotide synthesis as well as the one-carbon moieties used in DNA methylation reactions, two mechanisms which are frequently disrupted during carcinogenesis. While the use of folic acid for the chemoprevention of colorectal cancer is still controversial, there is evidence that folic acid intake has significant influence on these fundamental cellular mechanisms...
June 2015: Current Pharmacology Reports
Viviana Arroyo-Jousse, Diego F García-Díaz, Francisco Pérez-Bravo
BACKGROUND: The worldwide rise in the incidence of Type 1 Diabetes (T1D), and the concordance rate between monozygotic twins (50%), indicate a strong effect of the environment as an underlying factor of this disease. This process can occur throughout epigenetic modifications of gene expression such as DNA methylation, in which several nutrients participate as cofactors. AIM: To determine DNA methylation status in T1D patients and if it is related to plasma levels of folates and homocysteine (Hcy)...
May 2015: Revista Médica de Chile
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