title: Functionally conserved effects of rapamycin exposure on zebrafish.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara 06800, Turkey.
authors.forename: Ceren
authors.initials: C
authors.lastname: Sucularli
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara 06800, Turkey.
authors.forename: Huma
authors.initials: H
authors.lastname: Shehwana
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara 06800, Turkey.
authors.forename: Cem
authors.initials: C
authors.lastname: Kuscu
authors.affiliation: Biotechnology Institute, Ankara University, Ankara 06010, Turkey.
authors.forename: Dilay Ciglidag
authors.initials: DC
authors.lastname: Dungul
authors.affiliation: Biotechnology Institute, Ankara University, Ankara 06010, Turkey.
authors.forename: Hilal
authors.initials: H
authors.lastname: Ozdag
authors.affiliation: Department of Molecular Biology and Genetics, Faculty of Science, Bilkent University, Ankara 06800, Turkey.
authors.forename: Ozlen
authors.initials: O
authors.lastname: Konu
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D020123:Sirolimus / Q000494:pharmacology*; D013045:Species Specificity; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus