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Homocysteine and gene expression

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https://www.readbyqxmd.com/read/28701466/methionine-synthase-is-localized-to-the-nucleus-in-pichia-pastoris-and-candida-albicans-and-to-the-cytoplasm-in-saccharomyces-cerevisiae
#1
Umakant Sahu, Hunsur R Vinod Kumar, Shankar S Kapnoor, Raghu Bhagavat, Nagasuma Chandra, Pundi N Rangarajan
Methionine synthase (MS) catalyzes methylation of homocysteine, the last step in the biosynthesis of methionine, which is essential for the regeneration of tetrahydrofolate and biosynthesis of S-adenosyl methionine. Here, we report that MS is localized to the nucleus of Pichia pastoris and Candida albicans but cytoplasmic in Saccharomyces cerevisiaeP. pastoris strain carrying a deletion of MET6 gene encoding MS (Ppmet6) exhibits methionine as well as adenine auxotrophy indicating that MS is required for methionine as well as adenine biosynthesis...
July 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28633641/expression-levels-of-atherosclerosis-associated-mir-143-and-mir-145-in-the-plasma-of-patients-with-hyperhomocysteinaemia
#2
Kejian Liu, Saiyare Xuekelati, Yue Zhang, Yin Yin, Yue Li, Rui Chai, Xinwei Li, Yi Peng, Jiangdong Wu, Xiaomei Guo
BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients...
June 20, 2017: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/28579512/homocysteine-up-regulates-endothelin-type-a-receptor-in-vascular-smooth-muscle-cells-through-sirt1-erk1-2-signaling-pathway
#3
Yulong Chen, Huanhuan Liu, Xinhong Wang, Hongmei Zhang, Enqi Liu, Xingli Su
Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in cardiovascular diseases (CVDs). The endothelin type A (ETA) receptor is involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 2 (ERK1/2) signaling pathway is involved in regulation of the ETA receptor induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present study was designed to investigate the hypothesis that homocysteine up-regulates ETA receptor through the Sirt1/ERK1/2 signaling pathway...
June 1, 2017: Microvascular Research
https://www.readbyqxmd.com/read/28572511/clinical-or-atpase-domain-mutations-in-abcd4-disrupt-the-interaction-between-the-vitamin-b12-trafficking-proteins-abcd4-and-lmbd1
#4
Victoria Fettelschoss, Patricie Burda, Corinne Sagné, David Coelho, Corinne De Laet, Seraina Lutz, Terttu Suormala, Brian Fowler, Nicolas Pietrancosta, Bruno Gasnier, Beat Bornhauser, D Sean Froese, Matthias R Baumgartner
Vitamin B12 (cobalamin (Cbl)), in the cofactor forms methyl-Cbl and adenosyl-Cbl, is required for the function of the essential enzymes methionine synthase and methylmalonyl-CoA mutase, respectively. Cbl enters mammalian cells by receptor-mediated endocytosis of protein-bound Cbl followed by lysosomal export of free Cbl to the cytosol and further processing to these cofactor forms. The integral membrane proteins LMBD1 and ABCD4 are required for lysosomal release of Cbl, and mutations in the genes LMBRD1 and ABCD4 result in the cobalamin metabolism disorders cblF and cblJ...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546923/homocysteine-mediates-transcriptional-changes-of-the-inflammatory-pathway-signature-genes-in-human-retinal-pigment-epithelial-cells
#5
Mahavir Singh, Suresh C Tyagi
AIM: To test whether homocysteine (Hcy) can influence the transcriptional profile, we hypothesized that Hcy can lead to the induction of proinflammatory molecules in the retinal cells of aging people. METHODS: An unbiased in vitro inflammatory pathway focused study was designed employing retinal pigment epithelial (RPE) cell line, ARPE-19. Cells were cultured in the presence or absence of Hcy to capture target genes' expression profile. Three different concentrations of Hcy were added in the culture medium of confluent monolayers...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28489914/mir-27a-and-mir-449b-polymorphisms-associated-with-a-risk-of-idiopathic-recurrent-pregnancy-loss
#6
HyungChul Rah, Ki Wha Chung, Ki Han Ko, Eun Sun Kim, Jung Oh Kim, Jung Hyun Sakong, Ji Hyang Kim, Woo Sik Lee, Nam Keun Kim
OBJECTIVE: MicroRNAs (miRNAs) regulate gene expression during the peri-implantation period. The purpose of this study was to investigate whether genetic polymorphisms in the four miRNAs associated with fetal or placental development play roles in the development of idiopathic recurrent pregnancy loss (RPL) in Korean females. STUDY DESIGN: A case-control study involving 225 controls and 387 women with at least two consecutively recurrent pregnancy losses between 1999 and 2012 was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28488385/the-c-797-g-a-p-r266k-cystathionine-%C3%AE-synthase-mutation-causes-homocystinuria-by-affecting-protein-stability
#7
Sapna Gupta, Liqun Wang, Warren D Kruger
Mutations in the cystathionine beta-synthase (CBS) gene are the cause of classical homocystinuria, the most common inborn error in sulfur metabolism. The c.797 G>A (p.R266K) mutation in CBS was originally described in several Norwegian pyridoxine responsive CBS deficient patients, and heterologous gene expression studies have shown that the protein has near wild-type levels of enzyme activity. Here, we characterize a transgenic mouse lacking endogenous Cbs and expressing p.R266K human CBS protein from a zinc inducible metallothionein promoter (Tg-R266K Cbs(-/-) )...
July 2017: Human Mutation
https://www.readbyqxmd.com/read/28483519/microrna-384-mediated-herpud1-upregulation-promotes-angiotensin-ii-induced-endothelial-cell-apoptosis
#8
Hui Lin, Sunlei Pan, Liping Meng, Changzuan Zhou, Chengjian Jiang, Zheng Ji, Jufang Chi, Hangyuan Guo
BACKGROUND: Angiotensin II (Ang II)-induced damage to endothelial cells (ECs) plays a crucial role in the pathogenesis of atherosclerosis. This study aimed to investigate the role of microRNA-384 (miR-384) in endothelial cell apoptosis. METHODS: The expression of five various miRNAs in Ang II-treated human umbilical vein endothelial cells (HUVECs) were detected by qPCR. The Ang II-induced apoptosis of HUVECs was determined by flow cytometry, TUNEL staining and western blot...
July 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28475147/folic-acid-supplementation-delays-atherosclerotic-lesion-development-by-modulating-mcp1-and-vegf-dna-methylation-levels-in-vivo-and-in-vitro
#9
Shanshan Cui, Wen Li, Xin Lv, Pengyan Wang, Yuxia Gao, Guowei Huang
The pathogenesis of atherosclerosis has been partly acknowledged to result from aberrant epigenetic mechanisms. Accordingly, low folate levels are considered to be a contributing factor to promoting vascular disease because of deregulation of DNA methylation. We hypothesized that increasing the levels of folic acid may act via an epigenetic gene silencing mechanism to ameliorate atherosclerosis. Here, we investigated the atheroprotective effects of folic acid and the resultant methylation status in high-fat diet-fed ApoE knockout mice and in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells...
May 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28472596/reciprocal-regulation-between-mir-148a-152-and-dna-methyltransferase-1-is-associated-with-hyperhomocysteinemia-accelerated-atherosclerosis
#10
Anning Yang, Yue Sun, Yuan Gao, Songhao Yang, Caiyan Mao, Ning Ding, Mei Deng, Yanhua Wang, Xiaoling Yang, Yuexia Jia, Huiping Zhang, Yideng Jiang
DNA methyltransferase 1 (DNMT1) and miRNAs are both important regulators of gene expression that have been implicated in the pathogenesis of atherosclerosis. This study was designed to elucidate the potential interaction between DNMT1 and miRNAs in the context of hyperhomocysteinemia (HHcy)-related atherosclerosis. In the aorta of ApoE(-/-) mice fed a high methionine diet, increased expression of miR-148a/152, with decreased DNMT1 mRNA and protein levels, was detected. Similar changes were observed in cultured foam cells stimulated with homocysteine...
June 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28471487/folic-acid-is-necessary-for-proliferation-and-differentiation-of-c2c12-myoblasts
#11
Seong Y Hwang, Yong J Kang, Bokyung Sung, Jung Y Jang, Na L Hwang, Hye J Oh, Yu R Ahn, Hong J Kim, Jin H Shin, Mi-Ae Yoo, Cheol M Kim, Hae Y Chung, Nam D Kim
Folic acid, a water soluble B vitamin, plays an important role in cellular metabolic activities, such as functioning as a cofactor in one-carbon metabolism for DNA and RNA synthesis as well as nucleotide and amino acid biosynthesis in the body. A lack of dietary folic acid can lead to folic acid deficiency and result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and walking difficulty. However, the effect of folic acid deficiency on skeletal muscle development and its molecular mechanisms are unknown...
May 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28468239/choline-other-methyl-donors-and-epigenetics
#12
Steven Zeisel
Choline dietary intake varies such that many people do not achieve adequate intakes. Diet intake of choline can modulate methylation because, via betaine homocysteine methyltransferase (BHMT), this nutrient (and its metabolite, betaine) regulate the concentrations of S-adenosylhomocysteine and S-adenosylmethionine. Some of the epigenetic mechanisms that modify gene expression without modifying the genetic code depend on the methylation of DNA or of histones; and diet availability of choline and other methyl-group donors influences both of these methylations...
April 29, 2017: Nutrients
https://www.readbyqxmd.com/read/28446631/combined-vitamin-b-12-and-balanced-protein-energy-supplementation-affect-homocysteine-remethylation-in-the-methionine-cycle-in-pregnant-south-indian-women-of-low-vitamin-b-12-status
#13
RANDOMIZED CONTROLLED TRIAL
Sarita Devi, Arpita Mukhopadhyay, Pratibha Dwarkanath, Tinku Thomas, Julian Crasta, Annamma Thomas, C N Sheela, Jean W Hsu, Grace J Tang, Farook Jahoor, Anura V Kurpad
Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-μg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33)...
June 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28435838/thiol-trapping-and-metabolic-redistribution-of-sulfur-metabolites-enable-cells-to-overcome-cysteine-overload
#14
Anup Arunrao Deshpande, Muskan Bhatia, Sunil Laxman, Anand Kumar Bachhawat
Cysteine is an essential requirement in living organisms. However, due to its reactive thiol side chain, elevated levels of intracellular cysteine can be toxic and therefore need to be rapidly eliminated from the cellular milieu. In mammals and many other organisms, excess cysteine is believed to be primarily eliminated by the cysteine dioxygenase dependent oxidative degradation of cysteine, followed by the removal of the oxidative products. However, other mechanisms of tackling excess cysteine are also likely to exist, but have not thus far been explored...
March 27, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28397458/mapping-of-dna-hypermethylation-and-hypomethylation-induced-by-folate-deficiency-in-sporadic-colorectal-cancer-and-clinical-implication-analysis-of-hypermethylation-pattern-in-cbs-promoter
#15
Zaizhong Zhang, Yang He, Xiaohuang Tu, Sheng Huang, Zhuo Chen, Lie Wang, Jingxiang Song
BACKGROUND: Aberrant DNA methylation patterns play a major role in tumorigenesis and the effects of nutrients, especially folate in the diet, on methylation changes is of great importance in colorectal cancer (CRC). Folate deficiency would disrupt methylation patterns; however, its exact effects on DNA methylation patterns in CRC are unclear. This study was performed to gain insight into the methylation changes induced by folate deficiency and the putative role of methylation pattern diversities of related genes in the clinical outcome of CRC...
April 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28381354/1-25-dihydroxyvitamin-d3-prevents-deleterious-effects-of-homocysteine-on-mitochondrial-function-and-redox-status-in-heart-slices
#16
Aline Longoni, Janaina Kolling, Cassiana Siebert, João Paulo Dos Santos, Jussemara Souza da Silva, Letícia F Pettenuzzo, Leo Anderson Meira-Martins, Carlos-Alberto Gonçalves, Adriano M de Assis, Angela T S Wyse
Because homocysteine (Hcy) is a risk factor for cardiovascular disease, and vitamin D deficiency can contribute to cardiovascular pathologies. In the present study, we tested the hypothesis that Hcy could impair energy metabolism, mitochondrial function, and redox status in heart slices of Wistar rats and that 1,25-dihydroxivitamin D3 (calcitriol) treatment could prevent such effects. Heart slices were first pretreated with 3 different concentrations of calcitriol (50, 100, and 250nmol/L) for 30minutes at 37°C, after which Hcy was added to promote deleterious effects on metabolism...
February 2017: Nutrition Research
https://www.readbyqxmd.com/read/28374905/mtor-folate-sensing-links-folate-availability-to-trophoblast-cell-function
#17
Fredrick J Rosario, Theresa L Powell, Thomas Jansson
KEY POINTS: Folate deficiency during pregnancy is associated with restricted fetal growth, although the underlying mechanisms are poorly understood. Here we show that mechanistic target of rapamycin (mTOR) functions as a folate sensor in primary human trophoblast (PHT) cells. Folate sensing by mTOR in PHT cells involves both mTOR Complex 1 and 2 and requires the proton-coupled folate transporter. We report a previously unknown molecular mechanism by which folate regulates trophoblast cell function...
July 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28369960/chronic-alcohol-exposure-differentially-alters-one-carbon-metabolism-in-rat-liver-and-brain
#18
James Auta, Huaibo Zhang, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Epigenetic mechanisms such as DNA methylation play an important role in regulating the pathophysiology of alcoholism. Chronic alcohol exposure leads to behavioral changes as well as decreased expression of genes associated with synaptic plasticity. In the liver, it has been documented that chronic alcohol exposure impairs methionine synthase (Ms) activity leading to a decrease in S-adenosyl methionine/S-adenosyl homocysteine (SAM/SAH) ratio which results in DNA hypomethylation; however, it is not known whether similar alterations of SAM and SAH levels are also produced in brain...
June 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28368295/homocysteine-induces-hepatic-steatosis-involving-er-stress-response-in-high-methionine-diet-fed-mice
#19
Yanbiao Ai, Zhenzhen Sun, Chuan Peng, Lingli Liu, Xiaoqiu Xiao, Jibin Li
Elevated circulating homocysteine (Hcy) has been proposed to be associated with non-alcoholic fatty liver disease (NAFLD). It is also reported that Hcy causes protein misfolding in the endoplasmic reticulum (ER). In this study, we used a high methionine diet (HMD)-fed mouse model and cultured primary hepatocytes to investigate the effects of Hcy on hepatic lipids metabolism. C57BL/6J mice received either standard chow diet (CT, n = 10) or diet supplemented with 2% methionine (MET, n = 10) for 16 weeks. In in vitro experiments, cultured mouse primary hepatocytes were treated with Hcy, or Hcy combined with 4-phenylbutyric acid (4-PBA), or tunicamycin (TM), respectively...
April 1, 2017: Nutrients
https://www.readbyqxmd.com/read/28334897/genetic-absence-of-alox5-protects-from-homocysteine-induced-memory-impairment-tau-phosphorylation-and-synaptic-pathology
#20
Jian-Guo Li, Carlos Barrero, Salim Merali, Domenico Praticò
Elevated level of homocysteine (Hcy) is considered a risk factor for neurodegenerative diseases, but the mechanisms remain to be established. Because high Hcy is associated with an up-regulation of the ALOX5 gene product, the 5Lipoxygenase (5LO), herein we investigated whether this activation is responsible for the Hcy effect on neurodegeneration or is a secondary event. To reach this goal, wild type mice and mice genetically deficient for 5LO were assessed after being exposed to a diet known to significantly increase brain levels of Hcy...
May 15, 2017: Human Molecular Genetics
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