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  1. Article ; Online: Contribution of NAADP to Glutamate-Evoked Changes in Ca2+ Homeostasis in Mouse Hippocampal Neurons

    Julia Hermann / Melanie Bender / Dagmar Schumacher / Marcel S. Woo / Artem Shaposhnykov / Sina C. Rosenkranz / Vladimir Kuryshev / Chris Meier / Andreas H. Guse / Manuel A. Friese / Marc Freichel / Volodymyr Tsvilovskyy

    Frontiers in Cell and Developmental Biology, Vol

    2020  Volume 8

    Abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such ... ...

    Abstract Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such as TRPML1, the (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels as well as Ryanodine Receptors type 1 (RYR1; Guse, 2012). NAADP evokes calcium release from acidic calcium stores of many cell types (Guse, 2012), and NAADP-sensitive Ca2+ stores have been described in hippocampal neurons of the rat (Bak et al., 1999; McGuinness et al., 2007). Glutamate triggers Ca2+-mediated neuronal excitotoxicity in inflammation-induced neurodegenerative pathologies such as Multiple Sclerosis (MS; Friese et al., 2014), and when applied extracellularly to neurons glutamate can elevate NAADP levels in these cells. Accordingly, glutamate-evoked Ca2+ signals from intracellular organelles were inhibited by preventing organelle acidification (Pandey et al., 2009). Analysis of reported RNA sequencing experiments of cultured hippocampal neurons revealed the abundance of Mcoln1 (encoding TRPML1), Tpcn1, and Tpcn2 (encoding TPC1 and TPC2, respectively) as potential NAADP target channels in these cells. Transcripts encoding Ryr1 were not found in contrast to Ryr2 and Ryr3. To study the contribution of NAADP signaling to glutamate-evoked calcium transients in murine hippocampal neurons we used the NAADP antagonists Ned-19 (Naylor et al., 2009) and BZ194 (Dammermann et al., 2009). Our results show that both NAADP antagonists significantly reduce glutamate-evoked calcium transients. In addition to extracellular glutamate application, we studied synchronized calcium oscillations in the cells of the neuronal cultures evoked by addition of the GABAA receptor antagonist bicuculline. Pretreatment with Ned-19 (50 μM) or BZ194 (100 μM) led to an increase in the frequency of bicuculline-induced calcium oscillations at the cost of calcium transient amplitudes. Interestingly, ...
    Keywords hippocampal neurons ; glutamate ; NAADP ; Ca2+ homeostasis ; neuronal excitotoxicity ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Dependence of intracellular and exosomal microRNAs on viral E6/E7 oncogene expression in HPV-positive tumor cells.

    Anja Honegger / Daniela Schilling / Sandra Bastian / Jasmin Sponagel / Vladimir Kuryshev / Holger Sültmann / Martin Scheffner / Karin Hoppe-Seyler / Felix Hoppe-Seyler

    PLoS Pathogens, Vol 11, Iss 3, p e

    2015  Volume 1004712

    Abstract: Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of ... ...

    Abstract Specific types of human papillomaviruses (HPVs) cause cervical cancer. Cervical cancers exhibit aberrant cellular microRNA (miRNA) expression patterns. By genome-wide analyses, we investigate whether the intracellular and exosomal miRNA compositions of HPV-positive cancer cells are dependent on endogenous E6/E7 oncogene expression. Deep sequencing studies combined with qRT-PCR analyses show that E6/E7 silencing significantly affects ten of the 52 most abundant intracellular miRNAs in HPV18-positive HeLa cells, downregulating miR-17-5p, miR-186-5p, miR-378a-3p, miR-378f, miR-629-5p and miR-7-5p, and upregulating miR-143-3p, miR-23a-3p, miR-23b-3p and miR-27b-3p. The effects of E6/E7 silencing on miRNA levels are mainly not dependent on p53 and similarly observed in HPV16-positive SiHa cells. The E6/E7-regulated miRNAs are enriched for species involved in the control of cell proliferation, senescence and apoptosis, suggesting that they contribute to the growth of HPV-positive cancer cells. Consistently, we show that sustained E6/E7 expression is required to maintain the intracellular levels of members of the miR-17~92 cluster, which reduce expression of the anti-proliferative p21 gene in HPV-positive cancer cells. In exosomes secreted by HeLa cells, a distinct seven-miRNA-signature was identified among the most abundant miRNAs, with significant downregulation of let-7d-5p, miR-20a-5p, miR-378a-3p, miR-423-3p, miR-7-5p, miR-92a-3p and upregulation of miR-21-5p, upon E6/E7 silencing. Several of the E6/E7-dependent exosomal miRNAs have also been linked to the control of cell proliferation and apoptosis. This study represents the first global analysis of intracellular and exosomal miRNAs and shows that viral oncogene expression affects the abundance of multiple miRNAs likely contributing to the E6/E7-dependent growth of HPV-positive cancer cells.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 500
    Language English
    Publishing date 2015-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Integrative annotation of 21,037 human genes validated by full-length cDNA clones.

    Tadashi Imanishi / Takeshi Itoh / Yutaka Suzuki / Claire O'Donovan / Satoshi Fukuchi / Kanako O Koyanagi / Roberto A Barrero / Takuro Tamura / Yumi Yamaguchi-Kabata / Motohiko Tanino / Kei Yura / Satoru Miyazaki / Kazuho Ikeo / Keiichi Homma / Arek Kasprzyk / Tetsuo Nishikawa / Mika Hirakawa / Jean Thierry-Mieg / Danielle Thierry-Mieg /
    Jennifer Ashurst / Libin Jia / Mitsuteru Nakao / Michael A Thomas / Nicola Mulder / Youla Karavidopoulou / Lihua Jin / Sangsoo Kim / Tomohiro Yasuda / Boris Lenhard / Eric Eveno / Yoshiyuki Suzuki / Chisato Yamasaki / Jun-ichi Takeda / Craig Gough / Phillip Hilton / Yasuyuki Fujii / Hiroaki Sakai / Susumu Tanaka / Clara Amid / Matthew Bellgard / Maria de Fatima Bonaldo / Hidemasa Bono / Susan K Bromberg / Anthony J Brookes / Elspeth Bruford / Piero Carninci / Claude Chelala / Christine Couillault / Sandro J de Souza / Marie-Anne Debily / Marie-Dominique Devignes / Inna Dubchak / Toshinori Endo / Anne Estreicher / Eduardo Eyras / Kaoru Fukami-Kobayashi / Gopal R Gopinath / Esther Graudens / Yoonsoo Hahn / Michael Han / Ze-Guang Han / Kousuke Hanada / Hideki Hanaoka / Erimi Harada / Katsuyuki Hashimoto / Ursula Hinz / Momoki Hirai / Teruyoshi Hishiki / Ian Hopkinson / Sandrine Imbeaud / Hidetoshi Inoko / Alexander Kanapin / Yayoi Kaneko / Takeya Kasukawa / Janet Kelso / Paul Kersey / Reiko Kikuno / Kouichi Kimura / Bernhard Korn / Vladimir Kuryshev / Izabela Makalowska / Takashi Makino / Shuhei Mano / Regine Mariage-Samson / Jun Mashima / Hideo Matsuda / Hans-Werner Mewes / Shinsei Minoshima / Keiichi Nagai / Hideki Nagasaki / Naoki Nagata / Rajni Nigam / Osamu Ogasawara / Osamu Ohara / Masafumi Ohtsubo / Norihiro Okada / Toshihisa Okido / Satoshi Oota / Motonori Ota / Toshio Ota / Tetsuji Otsuki / Dominique Piatier-Tonneau / Annemarie Poustka / Shuang-Xi Ren / Naruya Saitou / Katsunaga Sakai / Shigetaka Sakamoto / Ryuichi Sakate / Ingo Schupp / Florence Servant / Stephen Sherry / Rie Shiba / Nobuyoshi Shimizu / Mary Shimoyama / Andrew J Simpson / Bento Soares / Charles Steward / Makiko Suwa / Mami Suzuki / Aiko Takahashi / Gen Tamiya / Hiroshi Tanaka / Todd Taylor / Joseph D Terwilliger / Per Unneberg / Vamsi Veeramachaneni / Shinya Watanabe / Laurens Wilming / Norikazu Yasuda / Hyang-Sook Yoo / Marvin Stodolsky / Wojciech Makalowski / Mitiko Go / Kenta Nakai / Toshihisa Takagi / Minoru Kanehisa / Yoshiyuki Sakaki / John Quackenbush / Yasushi Okazaki / Yoshihide Hayashizaki / Winston Hide / Ranajit Chakraborty / Ken Nishikawa / Hideaki Sugawara / Yoshio Tateno / Zhu Chen / Michio Oishi / Peter Tonellato / Rolf Apweiler / Kousaku Okubo / Lukas Wagner / Stefan Wiemann / Robert L Strausberg / Takao Isogai / Charles Auffray / Nobuo Nomura / Takashi Gojobori / Sumio Sugano

    PLoS Biology, Vol 2, Iss 6, p e

    2004  Volume 162

    Abstract: The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation ... ...

    Abstract The human genome sequence defines our inherent biological potential; the realization of the biology encoded therein requires knowledge of the function of each gene. Currently, our knowledge in this area is still limited. Several lines of investigation have been used to elucidate the structure and function of the genes in the human genome. Even so, gene prediction remains a difficult task, as the varieties of transcripts of a gene may vary to a great extent. We thus performed an exhaustive integrative characterization of 41,118 full-length cDNAs that capture the gene transcripts as complete functional cassettes, providing an unequivocal report of structural and functional diversity at the gene level. Our international collaboration has validated 21,037 human gene candidates by analysis of high-quality full-length cDNA clones through curation using unified criteria. This led to the identification of 5,155 new gene candidates. It also manifested the most reliable way to control the quality of the cDNA clones. We have developed a human gene database, called the H-Invitational Database (H-InvDB; http://www.h-invitational.jp/). It provides the following: integrative annotation of human genes, description of gene structures, details of novel alternative splicing isoforms, non-protein-coding RNAs, functional domains, subcellular localizations, metabolic pathways, predictions of protein three-dimensional structure, mapping of known single nucleotide polymorphisms (SNPs), identification of polymorphic microsatellite repeats within human genes, and comparative results with mouse full-length cDNAs. The H-InvDB analysis has shown that up to 4% of the human genome sequence (National Center for Biotechnology Information build 34 assembly) may contain misassembled or missing regions. We found that 6.5% of the human gene candidates (1,377 loci) did not have a good protein-coding open reading frame, of which 296 loci are strong candidates for non-protein-coding RNA genes. In addition, among 72,027 uniquely mapped SNPs and insertions/deletions localized within human genes, 13,215 nonsynonymous SNPs, 315 nonsense SNPs, and 452 indels occurred in coding regions. Together with 25 polymorphic microsatellite repeats present in coding regions, they may alter protein structure, causing phenotypic effects or resulting in disease. The H-InvDB platform represents a substantial contribution to resources needed for the exploration of human biology and pathology.
    Keywords Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2004-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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