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https://www.readbyqxmd.com/read/28230279/folate-protects-hepatocytes-of-hyperhomocysteinemia-mice-from-apoptosis-via-cystic-fibrosis-transmembrane-conductance-regulator-cftr-activated-endoplasmic-reticulum-stress
#1
Anning Yang, Yue Sun, Caiyan Mao, Songhao Yang, Min Huang, Mei Deng, Ning Ding, Xiaoling Yang, Minghao Zhang, Shaoju Jin, Yideng Jiang, Ying Huang
Folate deficiency is a known risk factor for liver injury; however, the underlying mechanism remains unclear. In this study, we employed a high homocysteine-induced liver injury model of Apolipoprotein E-deficient (ApoE(-/-) ) mice fed high-methionine diet and found that high homocysteine induced endoplasmic reticulum (ER) stress and liver cell apoptosis by downregulation of cystic fibrosis transmembrane conductance regulator (CFTR) expression; observations that were attenuated with supplementation of dietary folate...
February 23, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28229915/regulated-methionine-oxidation-by-monooxygenases
#2
REVIEW
Bruno Manta, Vadim N Gladyshev
Protein function can be regulated via post-translational modifications by numerous enzymatic and non-enzymatic mechanisms, including oxidation of cysteine and methionine residues. Redox-dependent regulatory mechanisms have been identified for nearly every cellular process, but the major paradigm has been that cellular components are oxidized (damaged) by reactive oxygen species (ROS) in a relatively unspecific way, and then reduced (repaired) by designated reductases. While this scheme may work with cysteine, it cannot be ascribed to other residues, such as methionine, whose reaction with ROS is too slow to be biologically relevant...
February 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28229434/preclinical-pharmacokinetics-and-pharmacodynamics-of-pinometostat-epz-5676-a-first-in-class-small-molecule-s-adenosyl-methionine-competitive-inhibitor-of-dot1l
#3
Nigel J Waters
Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias...
February 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28225105/elucidating-the-biosynthetic-pathways-of-volatile-organic-compounds-in-mycobacterium-tuberculosis-through-a-computational-approach
#4
Purva Bhatter, Karthik Raman, Vani Janakiraman
Microbial volatile organic compounds (VOCs) have gained prominence in the recent past for their potential use as disease markers. The discovery of microbial VOCs has benefited 'difficult to detect' diseases such as tuberculosis (TB). Few of the identified VOCs of Mycobacterium tuberculosis (Mtb) are currently being explored for their diagnostic potential. However, very little is known about the biosynthesis of these small lipophilic molecules. Here, we propose putative biosynthetic pathways in Mycobacterium tuberculosis for three VOCs, namely methyl nicotinate, methyl phenylacetate and methyl p-anisate, using computational approaches...
February 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28224386/%C3%AE-bisabolol-inhibits-aspergillus-fumigatus-af239-growth-via-affecting-microsomal-%C3%A2-24-sterol-methyltransferase-as-a-crucial-enzyme-in-ergosterol-biosynthesis-pathway
#5
Zahra Jahanshiri, Masoomeh Shams-Ghahfarokhi, Farnoush Asghari-Paskiabi, Reza Saghiri, Mehdi Razzaghi-Abyaneh
Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28221344/chemoproteomic-profiling-and-discovery-of-protein-electrophiles-in-human-cells
#6
Megan L Matthews, Lin He, Benjamin D Horning, Erika J Olson, Bruno E Correia, John R Yates, Philip E Dawson, Benjamin F Cravatt
Activity-based protein profiling (ABPP) serves as a chemical proteomic platform to discover and characterize functional amino acids in proteins on the basis of their enhanced reactivity towards small-molecule probes. This approach, to date, has mainly targeted nucleophilic functional groups, such as the side chains of serine and cysteine, using electrophilic probes. Here we show that 'reverse-polarity' (RP)-ABPP using clickable, nucleophilic hydrazine probes can capture and identify protein-bound electrophiles in cells...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28221022/quantitative-13c-traces-of-glucose-fate-in-hepatitis-b-virus-infected-hepatocytes
#7
Qianfen Wan, Yulan Wang, Huiru Tang
Quantitative characterization of 13C-labeled metabolites is an important part of the stable isotope tracing method widely used in metabolic flux analysis. Due to long relaxation time and low sensitivity of 13C nuclei, direct measurement of 13C labeled metabolites using one dimensional 13C NMR often fails to meet the demand of metabolomics studies especially with large number of samples and metabolites having low abundance. Although HSQC-based 2D NMR methods have improved sensitivity with inversion detection, they are time-consuming thus unsuitable for high-throughput absolute quantification of 13C-labeled metabolites...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28220495/influence-of-hyperglycemia-on-liver-inflammatory-conditions-in-the-early-phase-of-non-alcoholic-fatty-liver-disease-in-mice
#8
Shinichi Harada, Kei Miyagi, Tokio Obata, Yasuko Morimoto, Kazuo Nakamoto, Ke Ih Kim, Soo Ki Kim, Soo Ryang Kim, Shogo Tokuyama
OBJECTIVES: A non-alcoholic fatty liver disease (NAFLD) has high prevalence and now important issue of public health. In general, there exists strong interaction between NAFLD and diabetes, but the detailed mechanism is unclear. In this study, we determined the effects of hyperglycemia on progression in the early phase of NAFLD in mice. METHODS: Male ddY mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) consisting of 60% of kcal from fat and 0...
February 21, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#9
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219202/-precision-treatment-after-resistance-to-first-generation-egfr-tki-in-patients-with-non-small-cell-lung-cancer
#10
C Pi, Y C Zhang, C R Xu, Q Zhou
Recently, with the research progress in molecular classification, the treatment of advanced non-small cell lung cancer (NSCLC) has been established as a model of anti-tumor treatment of precision medicine. The discovery of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) has transformed the treatment of NSCLC from platinum based doublet chemotherapy into era of target therapy. EGFR-TKI, such as erlotinib and gefitinib, have been recommended as standard first-line treatment of patients with EGFR mutation...
February 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28218462/tungsten-exposure-causes-a-selective-loss-of-histone-demethylase-protein
#11
Freda Laulicht Glick, Feng Wu, Xiaoru Zhang, Ashley Jordan, Jason Brocato, Thomas Kluz, Hong Sun, Max Costa
In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28216563/the-genomic-impact-of-dna-cpg-methylation-on-gene-expression-relationships-in-prostate-cancer
#12
REVIEW
Mark D Long, Dominic J Smiraglia, Moray J Campbell
The process of DNA CpG methylation has been extensively investigated for over 50 years and revealed associations between changing methylation status of CpG islands and gene expression. As a result, DNA CpG methylation is implicated in the control of gene expression in developmental and homeostasis processes, as well as being a cancer-driver mechanism. The development of genome-wide technologies and sophisticated statistical analytical approaches has ushered in an era of widespread analyses, for example in the cancer arena, of the relationships between altered DNA CpG methylation, gene expression, and tumor status...
February 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28215807/proteomic-responses-of-european-flounder-to-temperature-and-hypoxia-as-interacting-stressors-differential-sensitivities-of-populations
#13
Nicolas Pédron, Sébastien Artigaud, José-Luis Zambonino Infante, Nicolas Le Bayon, Grégory Charrier, Vianney Pichereau, Jean Laroche
In the context of global change, ectotherms are increasingly impacted by abiotic perturbations. Along the distribution area of a species, the populations at low latitudes are particularly exposed to temperature increase and hypoxic events. In this study, we have compared the proteomic responses in the liver of European flounder populations, by using 2-D electrophoresis. One southern peripheral population from Portugal vs two northern core populations from France, were reared in a common garden experiment. Most of the proteomic differences were observed between the two experimental conditions, a cold vs a warm and hypoxic conditions...
February 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28214754/new-pt-nnso-core-anticancer-agents-structural-optimization-and-investigation-of-their-anticancer-activity
#14
Shu Xian Chong, Yinxue Jin, Steve Chik Fun Au-Yeung, Kenneth Kin Wah To
A series of new platinum Pt(II) compounds possessing a bidentate leaving ligand modified from oxaliplatin has been synthesized, with one of the oxygen ligating atom substituted for a sulphur atom (resulting in a Pt-NNSO coordination core structure). The general structures are R,R-diaminocyclohexane (DACH)-Pt-(methylthio)acetic acid (K4) and DACH-Pt-(thiophenylacetic acid) (K4 derivatives). Substitution of an electron donating or withdrawing group at the ortho or para position on the phenyl ring of K4 derivatives was found to affect the complexes' stability, reactivity with the biological molecules (5'-guanosine monophosphate (5'-GMP) and L-methionine (L-Met)) and anticancer activity...
February 12, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28214520/impact-of-copper-ligand-mutations-on-a-cupredoxin-with-a-green-copper-center
#15
Magali Roger, Giuliano Sciara, Frédéric Biaso, Elisabeth Lojou, Xie Wang, Marielle Bauzan, Marie-Thérèse Giudici-Orticoni, Alejandro Vila, Marianne Ilbert
Mononuclear cupredoxins contain a type 1 copper center with a trigonal or tetragonal geometry usually maintained by four ligands, a cystein, two histidines and a methionine. The recent discovery of new members of this family with unusual properties demonstrates, however, the versatility of this class of proteins. Changes in their ligand set lead to drastic variation in their metal site geometry and in the resulting spectroscopic and redox features. In our work, we report the identification of the copper ligands in the recently discovered cupredoxin AcoP...
February 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28212626/a-global-characterization-of-the-translational-and-transcriptional-programs-induced-by-methionine-restriction-through-ribosome-profiling-and-rna-seq
#16
Ke Zou, Qi Ouyang, Hao Li, Jiashun Zheng
BACKGROUND: Among twenty amino acids, methionine has a special role as it is coded by the translation initiation codon and methionyl-tRNAi (Met-tRNAi) is required for the assembly of the translation initiation complex. Thus methionine may play a special role in global gene regulation. Methionine has also been known to play important roles in cell growth, development, cancer, and aging. In this work, we characterize the translational and transcriptional programs induced by methionine restriction (MetR) and investigate the potential mechanisms through which methionine regulates gene expression, using the budding yeast S...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28210839/thrombotic-microangiopathy-caused-by-methionine-synthase-deficiency-diagnosis-and-treatment-pitfalls
#17
Maria Helena Vaisbich, Andressa Braga, Maria Gabrielle, Clarissa Bueno, Flávia Piazzon, Fernando Kok
BACKGROUND: Inborn errors of cobalamin (Cbl) metabolism form a large group of rare diseases. One of these, Cbl deficiency type C (CblC), is a well-known cause of thrombotic microangiopathy (TMA), especially in infants. However, there has only been a single published case of TMA associated to Cbl deficiency type G (CblG), also known as methionine synthase deficiency (MSD). CASE DIAGNOSIS/TREATMENT: A 21-month-old boy presented with pallor and oral ulcers during episodes of upper respiratory infection (URI)...
February 16, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28210795/observational-comparisons-of-intestinal-microbiota-characterizations-immune-enzyme-activities-and-muscle-amino-acid-compositions-of-loach-in-paddy-fields-and-ponds-in-sichuan-province
#18
Song Yang, Yuanliang Duan, Jie Zhang, Jian Zhou, Ya Liu, Jun Du, Liulan Zhao, Zongjun Du, Shuaishuai Han
A balanced intestinal microbial ecosystem is crucial for the growth and health of animals because it can influence the digestion and absorption of nutrients in the intestine. Different culture conditions may change the ecology of microbial in intestine and thus affect the overall growth performance of an animal. In this study, we compared intestinal morphologies, microbiota characterizations, immune enzyme activities, and muscle amino acid compositions of loach cultured in paddy fields and ponds. The fish were fed with the same diets from May 5 to November 5 (2015) in three paddy or ponds...
February 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28209762/identification-of-genes-in-saccharomyces-cerevisiae-that-are-haploinsufficient-for-overcoming-amino-acid-starvation
#19
Nancy S Bae, Andrew P Seberg, Leslie P Carroll, Mark J Swanson
The yeast Saccharomyces cerevisiae responds to amino acid deprivation by activating a pathway conserved in eukaryotes to overcome the starvation stress. We have screened the entire yeast heterozygous deletion collection to identify strains haploinsufficient for growth in the presence of sulfometuron methyl, which causes starvation for isoleucine and valine. We have discovered that cells devoid of MET15 are sensitive to sulfometuron methyl, and loss of heterozygosity at the MET15 locus can complicate screening the heterozygous deletion collection...
February 16, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28209181/de-novo-sequencing-and-comparative-transcriptome-analysis-of-adventitious-root-development-induced-by-exogenous-indole-3-butyric-acid-in-cuttings-of-tetraploid-black-locust
#20
Jine Quan, Seng Meng, Erhui Guo, Sheng Zhang, Zhong Zhao, Xitian Yang
BACKGROUND: Indole-3-butyric acid (IBA) is applied to the cuttings of various plant species to induce formation of adventitious roots (ARs) in commercial settings. Tetraploid black locust is an attractive ornamental tree that is drought resistant, sand tolerant, can prevent sand erosion and has various commercial uses. To further elucidate the mechanisms of AR formation, we used Illumina sequencing to analyze transcriptome dynamics and differential gene expression at four developmental stages in control (CK) and IBA-treated groups...
February 16, 2017: BMC Genomics
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