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https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#1
Wei Qiu, Ai-Li Zhang, Ye Tian
Tetrandrine (Tet), a potent lysosomal inhibitor, blocks autophagic flux and induces cancer cell death. Previously, the present authors identified the prostate cancer cell line DU145 to exhibit high sensitivity towards Tet in 11 cancer cell lines. In the present study, autophagy in Tet-treated DU145 cells was investigated. Similar to other cell lines, such as PC-3 and 786-O cells, Tet neutralized the acidity of lysosome and blocked autophagy in DU145 cells. However, Tet failed to induce microtubule-associated protein 1 light chain 3 (LC3) conversion in DU145 cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#2
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28521490/transcript-levels-of-ten-eleven-translocation-type-1-3-in-cervical-cancer-and-non-cancerous-cervical-tissues
#3
Dorota Ewa Bronowicka-Kłys, Andrzej Roszak, Piotr Pawlik, Stefan Sajdak, Anna Sowińska, Paweł Piotr Jagodziński
Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28516210/antibiotic-resistance-genes-in-surface-water-of-eutrophic-urban-lakes-are-related-to-heavy-metals-antibiotics-lake-morphology-and-anthropic-impact
#4
Yuyi Yang, Chen Xu, Xinhua Cao, Hui Lin, Jun Wang
Urban lakes are impacted by heavy human activities and represent potential reservoirs for antibiotic resistance genes. In this study, six urban lakes in Wuhan, central China were selected to analyze the distribution of sulfonamide resistance (sul) genes, tetracycline resistance (tet) genes and quinolone resistance (qnr) genes and their relationship with heavy metals, antibiotics, lake morphology and anthropic impact. sul1 and sul2 were detected in all six lakes and dominated the types of antibiotic resistance genes, which accounted for 86...
May 17, 2017: Ecotoxicology
https://www.readbyqxmd.com/read/28514756/elevated-crp-levels-predict-poor-outcome-and-tumor-recurrence-in-patients-with-thymic-epithelial-tumors-a-pro-and-retrospective-analysis
#5
Stefan Janik, Christine Bekos, Philipp Hacker, Thomas Raunegger, Bahil Ghanim, Elisa Einwallner, Lucian Beer, Walter Klepetko, Leonhard Müllauer, Hendrik J Ankersmit, Bernhard Moser
OBJECTIVE: Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs. RESULTS: Pretreatment CRP serum concentrations were significantly elevated in patients with TETs, particularly TCs and metastatic TETs. After complete tumor resection CRP serum concentrations were decreased (p = 0...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501652/a-new-adenovector-system-for-implementing-thymulin-gene-therapy-for-inflammatory-disorders
#6
María F Zappa-Villar, Micaela López-León, Joaquín Pardo, Mariana Costa, Rosana Crespo, Mireille Dardenne, Rodolfo G Goya, Paula C Reggiani
Thymulin is a thymic peptide possessing anti-inflammatory effects. In order to manipulate thymulin expression in gene therapy studies, we built a bidirectional regulatable two-vector Tet-Off system and the corresponding control system. The experimental two-vector system, ETV, consists of a recombinant adenovector (RAd) harboring an expression cassette centered on a Tet-Off bidirectional promoter flanked by a synthetic gene for thymulin and the gene for humanized Green Fluorescent Protein (hGFP). The second adenovector of this system, RAd-tTA, constitutively expresses the regulatory protein tTA...
May 11, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28481866/critical-role-of-myc-activation-in-mouse-hepatocarcinogenesis-induced-by-the-activation-of-akt-and-ras-pathways
#7
B Xin, M Yamamoto, K Fujii, T Ooshio, X Chen, Y Okada, K Watanabe, N Miyokawa, H Furukawa, Y Nishikawa
MYC activation at modest levels has been frequently found in hepatocellular carcinoma. However, its significance in hepatocarcinogenesis has remained obscure. Here we examined the role of Myc activation in mouse liver tumours induced by hepatocytic expression of myristoylated AKT (AKT) and/or mutant HRAS(V12) (HRAS) via transposon-mediated gene integration. AKT or HRAS alone required 5 months to induce liver tumours, whereas their combination generated hepatocellular carcinoma within 8 weeks. Co-introduction of AKT and HRAS induced lipid-laden preneoplastic cells that grew into nodules composed of tumour cells with or without intracytoplasmic lipid, with the latter being more proliferative and associated with spontaneous Myc expression...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28467834/nickel-ii-inhibits-tet-mediated-5-methylcytosine-oxidation-by-high-affinity-displacement-of-the-cofactor-iron-ii
#8
Ruichuan Yin, Jiezhen Mo, Jiayin Dai, Hailin Wang
Ten-eleven translocation (Tet) family proteins are Fe(II)- and 2-oxoglutarate-dependent dioxygenases that regulate the dynamics of DNA methylation by catalyzing the oxidation of DNA 5-methylcytosine (5mC). To exert physiologically important functions, redox-active iron chelated in the catalytic center of Tet proteins directly involves the oxidation of the multiple substrates. To understand the function and interaction network of Tet dioxygenases, it is interesting to obtain high affinity and a specific inhibitor...
May 8, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28456003/sodium-dependent-vitamin-c-transporter-2-deficiency-impairs-myelination-and-remyelination-after-injury-roles-of-collagen-and-demethylation
#9
Dominik Röhr, Hartmut Halfter, Jörg B Schulz, Peter Young, Burkhard Gess
Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen-containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28450733/tet-family-dioxygenases-and-dna-demethylation-in-stem-cells-and-cancers
#10
REVIEW
Jungeun An, Anjana Rao, Myunggon Ko
The methylation of cytosine and subsequent oxidation constitutes a fundamental epigenetic modification in mammalian genomes, and its abnormalities are intimately coupled to various pathogenic processes including cancer development. Enzymes of the Ten-eleven translocation (TET) family catalyze the stepwise oxidation of 5-methylcytosine in DNA to 5-hydroxymethylcytosine and further oxidation products. These oxidized 5-methylcytosine derivatives represent intermediates in the reversal of cytosine methylation, and also serve as stable epigenetic modifications that exert distinctive regulatory roles...
April 28, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28449087/methyl-cpg-binding-domain-protein-1-regulates-localization-and-activity-of-tet1-in-a-cxxc3-domain-dependent-manner
#11
Peng Zhang, Cathia Rausch, Florian D Hastert, Boyana Boneva, Alina Filatova, Sujit J Patil, Ulrike A Nuber, Yu Gao, Xinyu Zhao, M Cristina Cardoso
Cytosine modifications diversify and structure the genome thereby controlling proper development and differentiation. Here, we focus on the interplay of the 5-methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic subcellular localization and the formation of the Tet oxidation product 5-hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1 enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic DNA...
April 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28448110/heavy-metals-induce-decline-of-derivatives-of-5-methycytosine-in-both-dna-and-rna-of-stem-cells
#12
Jun Xiong, Xiaona Liu, Qing-Yun Cheng, Shan Xiao, Lai-Xin Xia, Bi-Feng Yuan, Yu-Qi Feng
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC)...
May 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#13
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28428226/rapid-throughput-analysis-of-gabaa-receptor-subtype-modulators-and-blockers-using-disbac1-3-membrane-potential-red-dye
#14
Atefeh Mousavi Nik, Brandon Pressly, Vikrant Singh, Shane Antrobus, Susan Hulsizer, Michael A Rogawski, Heike Wulff, Isaac N Pessah
Fluorometric Imaging Plate Reader (FLIPR®) membrane potential dye (FMP-Red-Dye) is a proprietary tool for basic discovery and high throughput drug screening for G-protein coupled receptors and ion channels. We optimized and validated this potentiometric probe to assay functional modulators of heterologous expressed GABAA receptor (GABAAR) isoforms (synaptic α1β3γ2, extrasynaptic α4β3δ, and β3 homopentomers). High-resolution mass spectrometry identified FMP-Red-dye as DisSBAC1(3). GABAAR expressing cells equilibrated with FMP-Red-Dye exhibited depolarized equilibrium membrane (Em) potentials compared to GABAAR-null cells...
April 20, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28411375/development-of-tetramethylenedisulfotetramine-tets-hapten-library-synthesis-electrophysiological-studies-and-immune-response-in-rabbits
#15
Bogdan Barnych, Natalia Vasylieva, Tom Joseph, Susan Hulsizer, Hai Nguyen, Tomas Cajka, Isaac Pessah, Heike Wulff, Shirley Gee, Bruce Hammock
There is a need for fast detection methods for the banned rodenticide tetramethylenedisulfotetramine (TETS), a highly potent blocker of the γ-aminobutyric acid (GABAA) receptors. General synthetic approach toward two groups of analogues was developed. Screening of the resulting library of compounds by FLIPR or whole-cell voltage-clamp revealed that despite the structural differences some of the TETS analogues retained GABAA receptor inhibition, however their potency was an order of magnitude lower. Antibodies raised in rabbits against some of the TETS analogues conjugated to protein recognized free TETS and will be used for the development of an immunoassay for TETS...
April 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28408905/tet-methylcytosine-oxidases-in-t-cell-and-b-cell-development-and-function
#16
REVIEW
Ageliki Tsagaratou, Chan-Wang J Lio, Xiaojing Yue, Anjana Rao
DNA methylation is established by DNA methyltransferases and is a key epigenetic mark. Ten-eleven translocation (TET) proteins are enzymes that oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidization products (oxi-mCs), which indirectly promote DNA demethylation. Here, we provide an overview of the effect of TET proteins and altered DNA modification status in T and B cell development and function. We summarize current advances in our understanding of the role of TET proteins and 5hmC in T and B cells in both physiological and pathological contexts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396520/cytosine-modifications-modulate-the-chromatin-architecture-of-transcriptional-enhancers
#17
Elise A Mahé, Thierry Madigou, Aurélien A Sérandour, Maud Bizot, Stéphane Avner, Frédéric Chalmel, Gaëlle Palierne, Raphaël Métivier, Gilles Salbert
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten Eleven Translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive...
April 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28393256/tetrandrine-inhibits-the-proliferation-of-human-osteosarcoma-cells-by-upregulating-the-pten-pathway
#18
Dong-Dong Tian, Ran-Xi Zhang, Nian Wu, Wei Yuan, Shuai-Hong Luo, Hou-Qing Chen, Yang Liu, Yang Wang, Bai-Cheng He, Zhong-Liang Deng
Tetrandrine (TET) is a natural product isolated from the Chinese herb Stephania tetrandra S. Moore and has been reported to have antiproliferation and apoptosis-inducing activity in various malignant tumor cells. However, the exact molecular mechanisms underlying these effects remain unclear. In the present study, we tested the antiproliferation effect of TET on osteosarcoma (OS) 143B cells and explored the possible potential molecular mechanism in this process. Using CCK-8 assay and flow cytometry, we found that TET inhibited proliferation, induced apoptosis and arrested the cell cycle of the 143B cells...
April 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28390956/the-structure-of-the-amorphous-matrix-of-keratins
#19
Murat Kadir, Xinwei Wang, Bowen Zhu, Jing Liu, Duane Harland, Crisan Popescu
Various keratin fibers, particularly human hairs, were investigated by transmission electron microscopy, TEM, solid-state (1)H NMR and Transient Electro-Thermal Technique, TET. The results converge to suggest that the matrix of keratin fiber cortex, far from being amorphous, has a well-defined nano-scale grainy structure, the size of these grains being around 2-4nm. The size of the grains appears to strongly depend on the chemical treatment of the fiber, on the temperature and on the relative humidity of the environment, as well as on the physiological factors at the level of fiber production in follicle...
April 5, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28360820/the-effect-of-tetrandrine-combined-with-cisplatin-on-proliferation-and-apoptosis-of-a549-ddp-cells-and-a549-cells
#20
Ling-Yun Ye, Song Hu, Hua-E Xu, Rong-Rong Xu, Hui Kong, Xiao-Ning Zeng, Wei-Ping Xie, Hong Wang
BACKGROUND: Non-small cell lung cancer comprises the majority of lung cancer cases and is insensitive to chemotherapy. Most patients develop drug resistance. Recently, tetrandrine (TET), a bis-benzylisoquinoline alkaloid, was identified as a novel anti-cancer agent. However, the effect of tetrandrine combined with cisplatin on lung cancer has not yet been studied. We aimed to identify a possible synergistic effect between tetrandrine and cisplatin, besides, to investigate the effects of TET in combination with DDP on proliferation and apoptosis in cisplatin-resistant and cisplatin-sensitive A549 cell lines, and to study the underlying mechanism...
2017: Cancer Cell International
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