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Homocysteine and gene expression

Shubhangi Prabhudesai, Chris Koceja, Anindya Dey, Shahram Eisa-Beygi, Noah R Leigh, Resham Bhattacharya, Priyabrata Mukherjee, Ramani Ramchandran
The cystathionine ß-synthase (CBS) is a critical enzyme in the transsulfuration pathway and is responsible for the synthesis of cystathionine from serine and homocysteine. Cystathionine is a precursor to amino acid cysteine. CBS is also responsible for generation of hydrogen sulfide (H2 S) from cysteine. Mutation in CBS enzyme causes homocysteine levels to rise, and gives rise to a condition called hyperhomocysteinuria. To date, numerous mouse knockout models for CBS enzyme has been generated, which show panoply of defects, reflecting the importance of this enzyme in development...
2018: Frontiers in Cell and Developmental Biology
Cassandra M Herring, Fuller W Bazer, Gregory A Johnson, Guoyao Wu
Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2 S that are generated from amino acid catabolism...
January 1, 2018: Experimental Biology and Medicine
Kejian Liu, Saiyare Xuekelati, Kang Zhou, Zhitao Yan, Xu Yang, Azeem Inayat, Jiangdong Wu, Xiaomei Guo
The aim of this study is to discuss the hypothesis that expression of plasma atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy) patients could predict the presence of atherosclerosis from different channels. Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30) selected for our study have been confirmed as critical gene regulators involved in atherosclerosis and can be steadily determined in plasma. Expression of the above six plasma circulating miRNAs revealed significant upregulation of two miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR-155, and miR-222)...
February 20, 2018: DNA and Cell Biology
Timothy J Bergmann, Ilaria Fregno, Fiorenza Fumagalli, Andrea Rinaldi, Francesco Bertoni, Paul J Boersema, Paola Picotti, Maurizio Molinari
The stress sensors ATF6, IRE1 and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to re-establish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans or redox homeostasis. Cell responses to variations in luminal load with unfolded proteins are, in contrast, poorly characterized...
February 16, 2018: Journal of Biological Chemistry
Zhen Hou, Qinwei Sun, Yun Hu, Shu Yang, Yibo Zong, Ruqian Zhao
As a feed additive, betaine is widely used in livestock production for its ability to promote growth. Our previous studies had reported that maternal betaine supplementation altered hepatic metabolism in offspring. But it remains unknown whether and how maternal betaine modulates metabolism of thyroid hormones in the offspring chickens by epigenetic modification. In this study, one hundred and twenty Rugao yellow-feathered laying hens were randomly divided into two groups, and were fed basal diet with or without 0...
February 13, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Tanusree Saha, Mahasweta Chatterjee, Deepak Verma, Anirban Ray, Swagata Sinha, Usha Rajamma, Kanchan Mukhopadhyay
An etiologically complex disorder, Attention Deficit Hyperactivity Disorder (ADHD), is often associated with various levels of cognitive deficit. Folate/vitamin B9 is crucial for numerous biochemical pathways including neural stem cell proliferation and differentiation, regulation of gene expression, neurotransmitter synthesis, myelin synthesis and repair, etc. and a scarcity has often been linked to cognitive deficit. Our pilot study in the field revealed significant association of few genetic variants with ADHD...
January 31, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
Shu Yang, Nannan Zhao, Yang Yang, Yun Hu, Haibo Dong, Ruqian Zhao
The growth-promoting action of betaine involves activation of GH/IGF-1 signaling, yet it remains unclear whether insulin-like growth factor 2 (IGF2), an imprinting gene, is affected by maternal dietary betaine supplementation. In this study, F1 offspring rats derived from dams fed basal or betaine-supplemented diet were examined at D21 and D63. Maternal betaine significantly upregulated the hepatic expression of IGF2 mRNA and protein in offspring rats at both D21 and D63, which was accompanied by enhanced hepatic IGF2 immunoreactivity and elevated serum IGF-2 level...
January 28, 2018: Journal of Agricultural and Food Chemistry
Radovan Murín, Eva Vidomanová, Bhavani S Kowtharapu, Jozef Hatok, Dušan Dobrota
Alterations in enzymatic activities underlying the cellular capacity to maintain functional S-adenosylmethionine (SAM) cycle are associated with modified levels of its constituents. Since SAM is the most prominent donor of methyl group for sustaining the methylation pattern of macromolecules by methyltransferases, its availability is an essential prerequisite for sustaining the methylation pattern of nucleic acids and proteins. In addition, increased intracellular concentrations of S-adenosylhomocysteine and homocysteine, another two constituents of SAM cycle, exerts an inhibitory effect on the enzymatic activity of methyltranferases...
December 2017: General Physiology and Biophysics
Ciria G Figueroa-Soto, Elisa M Valenzuela-Soto
For many years, glycine betaine (GB) has been widely studied as an osmolyte in plants and bacteria. In animal cells, GB is an osmolyte mainly in the kidneys, but in humans many studies have shown its role as a methyl donor in homocysteine metabolism in the liver. GB is also a protein stabilizer, and thus, it became known as an osmoprotector. In many organisms GB is synthesized from choline and can also be obtained from some foods. Over the last twenty years GB has gone from being considered simply as an osmolyte to being known as a cytoprotector involved in cell metabolism and as a chemical chaperone...
January 20, 2018: Biochimie
Lihua Wei, Shimei Zhao, Gaoxing Wang, Shiming Zhang, Weibo Luo, Zhengxue Qin, Xiongjie Bi, Yimei Tan, Moke Meng, Jun'an Qin, Huiping Qin, Dan Tian, An'wen Zhang
Atherosclerosis is a complicated process comprising inflammation, accumulation of collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important role in fibrosis and inflammation. In recent years, increasing research has concentrated on the connection between DNA methylation and atherosclerosis. The current study was designed to investigate methylation status of some specific gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship. We found that SMAD7 expression was decreased and its promoter region was markedly methylated in atherosclerotic plaques when compared with normal artery walls...
January 20, 2018: Biochemical and Biophysical Research Communications
Swarnalok De, Gabriela Chavez-Calvillo, Matti Wahlsten, Kristiina Mäkinen
Infection caused by synergistic interaction of two plant viruses is typically manifested by severe symptoms and increased accumulation of either virus. In potex-potyviral synergism potyviral RNA silencing suppressor HCPro is known to enhance the pathogenicity of the potexvirus counterpart. In line with this Potato virus X (PVX; genus Potexvirus) genomic RNA (gRNA) accumulation and gene expression from subgenomic RNA (sgRNA) increased in Nicotiana benthamiana by Potato virus A (PVA; genus Potyvirus) HCPro expression...
January 24, 2018: Molecular Plant Pathology
Kenneth R Eyring, Brent S Pedersen, Kenneth N Maclean, Sally P Stabler, Ivana V Yang, David A Schwartz
RATIONALE: Environmental exposures strongly influence the development and progression of asthma. We have previously demonstrated that mice exposed to a diet enriched with methyl donors during vulnerable periods of fetal development can enhance the heritable risk of allergic airway disease through epigenetic changes. There is conflicting evidence on the role of folate (one of the primary methyl donors) in modifying allergic airway disease. OBJECTIVES: We hypothesized that blocking folate metabolism through the loss of methylene-tetrahydrofolate reductase (Mthfr) activity would reduce the allergic airway disease phenotype through epigenetic mechanisms...
2018: PloS One
Lian Duan, Ling Wei, Yanghua Tian, Zhengshan Zhang, Panpan Hu, Qiang Wei, Sugang Liu, Jun Zhang, Yuyang Wang, Desheng Li, Weizhong Yang, Rui Zong, Peng Xian, Cong Han, Xiangyang Bao, Feng Zhao, Jie Feng, Wei Liu, Wuchun Cao, Guoping Zhou, Chunyan Zhu, Fengqiong Yu, Weimin Yang, Yu Meng, Jingye Wang, Xianwen Chen, Yu Wang, Bing Shen, Bing Zhao, Jinghai Wan, Fengyu Zhang, Gang Zhao, Aimin Xu, Xuejun Zhang, Jianjun Liu, Xianbo Zuo, Kai Wang
BACKGROUND AND PURPOSE: Moyamoya disease (MMD) is a rare cerebral vasculopathy characterized by bilateral internal carotid artery stenosis and often leads to stroke in children or young adults. Although familial inheritance is well recognized, the genetic basis of MMD remains poorly understood. METHODS: A 2-stage genome-wide association study was conducted involving 1492 cases and 5084 controls. In the discovery stage, logistic regression was used to test associations, and imputation was conducted based on genotyped single-nucleotide polymorphisms (SNPs)...
January 2018: Stroke; a Journal of Cerebral Circulation
Evan C Lien, Laura Ghisolfi, Renee C Geck, John M Asara, Alex Toker
The precursor homocysteine is metabolized either through the methionine cycle to produce methionine or through the transsulfuration pathway to synthesize cysteine. Alternatively, cysteine can be obtained through uptake of its oxidized form, cystine. Many cancer cells exhibit methionine dependency such that their proliferation is impaired in growth media in which methionine is replaced by homocysteine. We showed that oncogenic PIK3CA and decreased expression of SLC7A11, a gene that encodes a cystine transporter also known as xCT, correlated with increased methionine dependency in breast cancer cells...
December 19, 2017: Science Signaling
Shanshan Cui, Wen Li, Pengyan Wang, Xin Lv, Yuxia Gao, Guowei Huang
Homocysteine may be responsible for vascular endothelial cell injury, which occurs early in the pathology of cardiovascular disease. Homocysteine metabolism requires enzymatic interaction with vitamins such as folic acid, vitamin B12, and vitamin B6. We hypothesized that folic acid alleviated homocysteine-induced vascular injury by regulating the metabolic pathway of apoptosis. Human umbilical vein endothelial cells were incubated for 48 h with folic acid at the concentrations of 0-1000 nmol/L, in combination with either 1000 μmol/L homocysteine or vehicle for the first 24 h...
December 18, 2017: Molecular and Cellular Biochemistry
Yu-Xin Bai, Fang Fang, Jia-Ling Jiang, Feng Xu
BACKGROUND Lung alveolar epithelial type II cells (AEC II) are the most important stem cells in lung tissues, which are critical for wound repair of bronchopulmonary dysplasia (BPD). This study investigated the effects of calcitonin gene-related peptide (CGRP) on AEC II cells exposed to hyperoxia. MATERIAL AND METHODS Neonatal rat AEC II cells were isolated and identified by detecting surfactant protein C (SP-C). Three small interfering RNAs targeting Notch 1 were synthesized and transfected into AEC II. A hyperoxia-exposed AEC II cell injury model was established and was divided into 8 groups...
December 5, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Li Wu, Xihong Zhou, Tiejun Li, Juyun He, Linli Huang, Zicheng Ouyang, Liuqin He, Tao Wei, Qinghua He
Zinc plays a role in alleviating oxidative stress. However, the related mechanisms remain to be further elucidated. The present study was conducted to investigate whether the recovery of oxidative stress in high-fat-diet (HFD)-pretreated mice was affected by zinc. Male mice received either an HFD or a low-fat-diet (LFD) for 8 weeks. Then, the mice fed with HFD and LFD were both assigned to either a control diet (30 mg zinc, ZD) or a no-added zinc diet (NZD) for an additional 4 weeks. The results showed that after feeding with NZD for 4 weeks, the HFD-pretreated mice had the highest plasma glucose and insulin concentrations, while had the lowest CuZn-SOD and glutathione concentrations...
December 4, 2017: Biological Trace Element Research
Erica M Weekman, Abigail E Woolums, Tiffany L Sudduth, Donna M Wilcock
High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr...
November 2017: ASN Neuro
María A Pajares, Dolores Pérez-Sala
SIGNIFICANCE: Transsulfuration allows conversion of methionine into cysteine using homocysteine (Hcy) as an intermediate. This pathway produces S-adenosylmethionine (AdoMet), a key metabolite for cell function, and provides 50% of the cysteine needed for hepatic glutathione synthesis. The route requires the intake of essential nutrients (e.g., methionine and vitamins) and is regulated by their availability. Transsulfuration presents multiple interconnections with epigenetics, adenosine triphosphate (ATP), and glutathione synthesis, polyol and pentose phosphate pathways, and detoxification that rely mostly in the exchange of substrates or products...
January 9, 2018: Antioxidants & Redox Signaling
Daniel Berner, Matthias Zenkel, Francesca Pasutto, Ursula Hoja, Panah Liravi, Gabriele C Gusek-Schneider, Friedrich E Kruse, Johannes Schödel, Andre Reis, Ursula Schlötzer-Schrehardt
Purpose: Alternative mRNA splicing coupled to nonsense-mediated decay (NMD) is a common mRNA surveillance pathway also known to dynamically modulate gene expression in response to cellular stress. Here, we investigated the involvement of this pathway in the regulation of lysyl oxidase-like 1 (LOXL1) expression in response to pseudoexfoliation (PEX)-associated pathophysiologic factors. Methods: Transcript levels of LOXL1 isoforms were determined in ocular tissues obtained from donor eyes without and with PEX syndrome...
November 1, 2017: Investigative Ophthalmology & Visual Science
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