title: Zebrafish as a model organism to evaluate drugs potentially able to modulate sirtuin expression.
abstract: Sirtuins comprise a unique class of NAD(+)-dependent deacetylases that are key regulators of many physiological processes. They appear to be a potential target set of enzymes for treatment of age-associated diseases and have attracted interest in many research areas involving chemical and cellular investigations to understand them and discover potential ligands. For molecular screening, a cost-effective, easily manipulated, and consolidated model organism is needed, and the zebrafish fits these requirements perfectly. Here, we report the identification of sirtuin-related genes and their expression patterns in nine tissues of adult zebrafish. The investigation identified eight sirtuin-related genes, and their phylogenetic analysis resulted in seven well-resolved terminal clades, corresponding to each sirtuin (SIRT1, 2, 4-7) and two SIRT3 paralogs. Each gene showed a unique expression profile, illustrating a wide tissue distribution of sirtuins in zebrafish. SIRT1, SIRT3, SIRT5, and SIRT6 genes were expressed in all tissues, and SIRT1 exhibited the highest level of expression in all organs. A modulation experiment was performed using resveratrol, and results confirmed to the predicted scenario: altered sirtuin expression levels. Drugs based on sirtuin modulators may be tested using this system and could lead us to more selective and powerful therapies for age-related disorders.
authors.affiliation: Laboratório de Biologia Genômica e Molecular, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Talita Carneiro Brandão
authors.initials: TC
authors.lastname: Pereira
authors.forename: Eduardo Pacheco
authors.initials: EP
authors.lastname: Rico
authors.forename: Denis Broock
authors.initials: DB
authors.lastname: Rosemberg
authors.forename: Helena
authors.initials: H
authors.lastname: Schirmer
authors.forename: Renato Dutra
authors.initials: RD
authors.lastname: Dias
authors.forename: André Arigony
authors.initials: AA
authors.lastname: Souto
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
authors.forename: Maurício Reis
authors.initials: MR
authors.lastname: Bogo
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D010802:Phylogeny; D000077185:Resveratrol; D037761:Sirtuins / Q000235:genetics* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013267:Stilbenes; D029961:Zebrafish Proteins; D037761:Sirtuins; D000077185:Resveratrol