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Tet proteins

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https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#1
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642344/a-role-for-tet2-in-parathyroid-carcinoma
#2
Elham Barazeghi, Anthony J Gill, Stan Sidhu, Olov Norlén, Roberto Dina, F Fausto Palazzo, Per Hellman, Peter Stålberg, Gunnar Westin
Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of TET1 and TET2 play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases...
July 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28629934/recent-advances-in-leishmania-reverse-genetics-manipulating-a-manipulative-parasite
#3
REVIEW
Samuel M Duncan, Nathaniel G Jones, Jeremy C Mottram
In this review we describe the expanding repertoire of molecular tools with which to study gene function in Leishmania. Specifically we review the tools available for studying functions of essential genes, such as plasmid shuffle and DiCre, as well as the rapidly expanding portfolio of available CRISPR/Cas9 approaches for large scale gene knockout and endogenous tagging. We include detail on approaches that allow the direct manipulation of RNA using RNAi and protein levels via Tet or DiCre induced overexpression and destabilization domain mediated degradation...
June 16, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28623268/ascorbate-induces-apoptosis-in-melanoma-cells-by-suppressing-clusterin-expression
#4
Sushmita Mustafi, David W Sant, Zhao-Jun Liu, Gaofeng Wang
Pharmacological levels of ascorbate have long been suggested as a potential treatment of cancer. However, we observed that EC50 of ascorbate was at a similar level for cultured healthy melanocytes and melanoma cells, suggesting a limit of pharmacological ascorbate in treating cancer. Loss of 5-hydroxymethylcytosine (5 hmC) is an epigenetic hallmark of cancer and ascorbate promotes 5 hmC generation by serving as a cofactor for TET methylcytosine dioxygenases. Our previous work demonstrated that ascorbate treatment at physiological level (100 μM) increased 5 hmC content in melanoma cells toward the level of healthy melanocytes...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28613399/immunosuppressive-efficacy-of-tetrandrine-combined-with-methylprednisolone-against-mitogen-activated-peripheral-blood-mononuclear-cells-of-hemodialysis-patients
#5
Wencheng Xu, Kehan Meng, Junichi Kusano, Hiroto Matsuda, Yoshikazu Hara, Yoshiaki Fujii, Shinya Suzuki, Eiki Ando, Xiaoqin Wang, Yuanchao Tu, Sachiko Tanaka, Kentaro Sugiyama, Haruki Yamada, Toshihiko Hirano
Immunosuppressive therapy for prevention of acute rejection episode occasionally causes serious adverse effects, and thus it is important to develop new therapeutic approach for renal transplant recipients. This study evaluated the immunosuppressive pharmacodynamics of tetrandrine (TET) and/or methylprednisolone (MP) in hemodialysis patients in vitro by using the peripheral blood mononuclear cells (PBMCs) isolated from whole blood of hemodialysis patients. The median (range) of MP IC50 values against the proliferation of patients PBMCs was 7...
June 14, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28609472/no-evidence-for-genome-editing-in-mouse-zygotes-and-hek293t-human-cell-line-using-the-dna-guided-natronobacterium-gregoryi-argonaute-ngago
#6
Nay Chi Khin, Jenna L Lowe, Lora M Jensen, Gaetan Burgio
A recently published research article reported that the extreme halophile archaebacterium Natronobacterium gregoryi Argonaute enzyme (NgAgo) could cleave the cellular DNA under physiological temperature conditions in cell line and be implemented as an alternative to CRISPR/Cas9 genome editing technology. We assessed this claim in mouse zygotes for four loci (Sptb, Tet-1, Tet-2 and Tet-3) and in the human HEK293T cell line for the EMX1 locus. Over 100 zygotes were microinjected with nls-NgAgo-GK plasmid provided from Addgene and various concentrations of 5'-phosphorylated guide DNA (gDNA) from 2...
2017: PloS One
https://www.readbyqxmd.com/read/28607447/fam83h-is-involved-in-the-progression-of-hepatocellular-carcinoma-and-is-regulated-by-myc
#7
Kyoung Min Kim, See-Hyoung Park, Jun Sang Bae, Sang Jae Noh, Guo-Zhong Tao, Jung Ryul Kim, Keun Sang Kwon, Ho Sung Park, Byung-Hyun Park, Ho Lee, Myoung Ja Chung, Woo Sung Moon, Karl G Sylvester, Kyu Yun Jang
Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28601635/silencing-hif-1%C3%AE-induces-tet2-expression-and-augments-ascorbic-acid-induced-5-hydroxymethylation-of-dna-in-human-metastatic-melanoma-cells
#8
Adam P Fischer, Sarah L Miles
Expression and function of Ten-eleven translocation (TET) enzymes, which initiate DNA demethylation by catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5 hmC) on methylated DNA, are frequently lost in malignant tissue. This ultimately results in lost expression of methylated tumor suppressor genes. Many malignancies, including melanoma, also aberrantly overexpress the oncogenic hypoxia inducible factor-1α (HIF-1α) transcription factor, however the association between HIF-1α and TET enzyme expression is largely uninvestigated...
June 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28600952/time-course-of-tau-toxicity-and-pharmacologic-prevention-in-a-cell%C3%A2-model-of-tauopathy
#9
Marcus Pickhardt, Jacek Biernat, Sabrina Hübschmann, Frank J A Dennissen, Thomas Timm, Annukka Aho, Eva-Maria Mandelkow, Eckhard Mandelkow
The aggregation of Tau protein is a hallmark of neurodegenerative diseases including Alzheimer's disease. Previously, we generated a cell model of tauopathy based on the 4-repeat domain with the FTDP-17 mutation ΔK280 (Tau(4RDΔK)) which is expressed in a regulatable fashion (tet-on). The deletion variant ΔK280 is highly amyloidogenic and forms fibrous aggregates in neuroblastoma N2a cells staining with the reporter dye Thioflavin S. The aggregation of Tau(4RDΔK) is toxic, contrary to wildtype or anti-aggregant variants of the protein...
May 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28597304/improved-tet-on-and-tet-off-systems-for-tetracycline-regulated-expression-of-genes-in-candida
#10
Swati Bijlani, Anubhav S Nahar, K Ganesan
Tetracycline-regulated expression of genes is often used for functional analysis of Candida albicans genes. However, the widely used Tet-On system has certain limitations such as prolonged lag time (up to 8 h) for induction and non-uniform expression among the cells. We speculated that poor expression of tetracycline-controlled transactivator (Tet-transactivator) from CaADH1 promoter could be responsible for this, and thus compared the effect of expressing this protein under the control of CaADH1, CaTDH3 and CaRP10 promoters on the expression of GFP from the TET promoter...
June 8, 2017: Current Genetics
https://www.readbyqxmd.com/read/28596758/a-functional-metagenomic-analysis-of-tetracycline-resistance-in-cheese-bacteria
#11
Ana B Flórez, Lucía Vázquez, Baltasar Mayo
Metagenomic techniques have been successfully used to monitor antibiotic resistance genes in environmental, animal and human ecosystems. However, despite the claim that the food chain plays a key role in the spread of antibiotic resistance, metagenomic analysis has scarcely been used to investigate food systems. The present work reports a functional metagenomic analysis of the prevalence and evolution of tetracycline resistance determinants in a raw-milk, blue-veined cheese during manufacturing and ripening...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28574626/assessment-of-phenotypic-and-genotypic-antibiotic-susceptibility-of-vaginal-lactobacillus-sp
#12
Jelena Štšepetova, Heleri Taelma, Imbi Smidt, Pirje Hütt, Eleri Lapp, Evi Aotäht, Reet Mändar
AIM: To assess antibiotic susceptibility of vaginal lactobacilli strains and provide the data required for assessing the potential of antibiotic resistance risk of new strains selected as probiotic. METHODS AND RESULTS: Potential probiotic vaginal lactobacilli used in the study included 31 vaginal strains of Lactobacillus crispatus, (n=27), L. gasseri (n=3) and L. jensenii (n=1) obtained from the collection of Competence Centre on Health Technologies. Two commercial probiotic strains were used as controls (L...
June 2, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28529589/tetrandrine-triggers-an-alternative-autophagy-in-du145-cells
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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