Sucularli, C.Shehwana, H.Kuscu, C.Dungul, D. C.Ozdag, H.Konu, O.2018-04-122018-04-122016-031791-2997http://hdl.handle.net/11693/36466Mechanistic 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.EnglishMeta-analysisMicroarrayMousemTORRapamycinReal-time qPCRZebrafishZF4Aromatic levo amino acid decarboxylaseCytochrome P450Cytochrome P450 26B1Dickkopf 1 proteinDickkopf 1b proteinMessenger RNAPhenylalanine 4 monooxygenaseProteasomeProteinRapamycinTranscription factorTranscription factor FOXM1TranscriptomeUnclassified drugWNT inhibitory factor 1RapamycinTarget of rapamycin kinaseZebrafish proteinAnimal cellAnimal cell cultureAnimal experimentApoptosisArticleBody sizeCell cycleCell metabolismCell proliferationCell viabilityControlled studyDNA synthesisDown regulationDrug effectDrug exposureEmbryoEmbryo growthEndoplasmic reticulumFibroblast cultureGene expressionGenetic conservationMicroarray analysisMitochondrionMouseNonhumanOxidative phosphorylationPigmentationProtein synthesisRibosome subunitSteady stateUpregulationZebra fishAnimalCell lineComparative studyDrug effectsGene expression regulationMetabolismSpecies differenceZebra fishAnimalsCell LineGene Expression RegulationMiceSirolimusSpecies SpecificityTOR Serine-Threonine KinasesZebrafishZebrafish ProteinsArticle10.3892/mmr.2016.5059