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      Functionally conserved effects of rapamycin exposure on zebrafish

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      Author(s)
      Sucularli, C.
      Shehwana, H.
      Kuscu, C.
      Dungul, D. C.
      Ozdag, H.
      Konu, O.
      Date
      2016-03
      Source Title
      Molecular Medicine Reports
      Print ISSN
      1791-2997
      Publisher
      Spandidos Publications
      Volume
      13
      Issue
      5
      Pages
      4421 - 4430
      Language
      English
      Type
      Article
      Item Usage Stats
      151
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      91
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      Abstract
      Mechanistic target of rapamycin (mTOR) is a conserved serine/threonine kinase important in cell proliferation, growth and protein translation. Rapamycin, a well-known anti-cancer agent and immunosuppressant drug, inhibits mTOR activity in different taxa including zebrafish. In the present study, the effect of rapamycin exposure on the transcriptome of a zebrafish fibroblast cell line, ZF4, was investigated. Microarray analysis demonstrated that rapamycin treatment modulated a large set of genes with varying functions including protein synthesis, assembly of mitochondrial and proteasomal machinery, cell cycle, metabolism and oxidative phosphorylation in ZF4 cells. A mild however, coordinated reduction in the expression of proteasomal and mitochondrial ribosomal subunits was detected, while the expression of numerous ribosomal subunits increased. Meta-analysis of heterogeneous mouse rapamycin microarray datasets enabled the comparison of zebrafish and mouse pathways modulated by rapamycin, using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology pathway analysis. The analyses demonstrated a high degree of functional conservation between zebrafish and mice in response to rapamycin. In addition, rapamycin treatment resulted in a marked dose-dependent reduction in body size and pigmentation in zebrafish embryos. The present study is the first, to the best of our knowledge, to evaluate the conservation of rapamycin-modulated functional pathways between zebrafish and mice, in addition to the dose-dependent growth curves of zebrafish embryos upon rapamycin exposure.
      Keywords
      Meta-analysis
      Microarray
      Mouse
      mTOR
      Rapamycin
      Real-time qPCR
      Zebrafish
      ZF4
      Aromatic levo amino acid decarboxylase
      Cytochrome P450
      Cytochrome P450 26B1
      Dickkopf 1 protein
      Dickkopf 1b protein
      Messenger RNA
      Phenylalanine 4 monooxygenase
      Proteasome
      Protein
      Rapamycin
      Transcription factor
      Transcription factor FOXM1
      Transcriptome
      Unclassified drug
      WNT inhibitory factor 1
      Rapamycin
      Target of rapamycin kinase
      Zebrafish protein
      Animal cell
      Animal cell culture
      Animal experiment
      Apoptosis
      Article
      Body size
      Cell cycle
      Cell metabolism
      Cell proliferation
      Cell viability
      Controlled study
      DNA synthesis
      Down regulation
      Drug effect
      Drug exposure
      Embryo
      Embryo growth
      Endoplasmic reticulum
      Fibroblast culture
      Gene expression
      Genetic conservation
      Microarray analysis
      Mitochondrion
      Mouse
      Nonhuman
      Oxidative phosphorylation
      Pigmentation
      Protein synthesis
      Ribosome subunit
      Steady state
      Upregulation
      Zebra fish
      Animal
      Cell line
      Comparative study
      Drug effects
      Gene expression regulation
      Metabolism
      Species difference
      Zebra fish
      Animals
      Cell Line
      Gene Expression Regulation
      Mice
      Sirolimus
      Species Specificity
      TOR Serine-Threonine Kinases
      Zebrafish
      Zebrafish Proteins
      Permalink
      http://hdl.handle.net/11693/36466
      Published Version (Please cite this version)
      https://doi.org/10.3892/mmr.2016.5059
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      • Department of Molecular Biology and Genetics 468
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