Functionally conserved effects of rapamycin exposure on zebrafish
Date
2016-03Source Title
Molecular Medicine Reports
Print ISSN
1791-2997
Publisher
Spandidos Publications
Volume
13
Issue
5
Pages
4421 - 4430
Language
English
Type
ArticleItem Usage Stats
151
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91
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downloads
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-analysisMicroarray
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/11693/36466Published Version (Please cite this version)
https://doi.org/10.3892/mmr.2016.5059Collections
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