RESUMO
Crude oils from distinct geographical regions have distinct chemical compositions, and, as a result, their toxicity may be different. However, developmental toxicity of crude oils derived from different geographical regions has not been extensively characterized. In this study, flounder embryos were separately exposed to effluents contaminated by three crude oils including: Basrah Light (BLO), Pyrenees (PCO), and Sakhalin Vityaz (SVO), in addition to a processed fuel oil (MFO-380), to measure developmental toxicity and for gene expressions. Each oil possessed a distinct chemical composition. Edema defect was highest in embryos exposed to PCO and MFO-380 that both have a greater fraction of three-ring PAHs (33% and 22%, respectively) compared to BLO and SVO. Observed caudal fin defects were higher in embryos exposed to SVO and MFO-380, which are both dominated by naphthalenes (81% and 52%, respectively). CYP1A gene expressions were also highest in embryos exposed to SVO and MFO-380. Higher incidence of cardiotoxicity and lower nkx 2.5 expression were detected in embryos exposed to PCO. Unique gene expression profiles were observed in embryos exposed to crude oils with distinct compositions. This study demonstrates that crude oils of different geographical origins with different compositional characteristics induce developmental toxicity to different degrees.
Assuntos
Proteínas de Peixes/metabolismo , Linguado/embriologia , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Morfogênese/efeitos dos fármacos , Petróleo/toxicidade , Teratogênicos/toxicidade , Poluentes Químicos da Água/toxicidade , Nadadeiras de Animais/anormalidades , Nadadeiras de Animais/efeitos dos fármacos , Nadadeiras de Animais/embriologia , Animais , Aquicultura , Austrália , Família 1 do Citocromo P450/química , Família 1 do Citocromo P450/genética , Família 1 do Citocromo P450/metabolismo , Proteínas de Peixes/agonistas , Proteínas de Peixes/antagonistas & inibidores , Proteínas de Peixes/genética , Linguado/anormalidades , Linguado/metabolismo , Óleos Combustíveis/análise , Óleos Combustíveis/toxicidade , Perfilação da Expressão Gênica , Coração/efeitos dos fármacos , Coração/embriologia , Proteína Homeobox Nkx-2.5/antagonistas & inibidores , Proteína Homeobox Nkx-2.5/genética , Proteína Homeobox Nkx-2.5/metabolismo , Iraque , Naftalenos/análise , Naftalenos/toxicidade , Petróleo/análise , Poluição por Petróleo/efeitos adversos , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Federação Russa , Teratogênicos/análise , Teratogênicos/química , Testes de Toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/químicaRESUMO
Class IIa histone deacetylases (HDACs) are very important for tissue specific gene regulation in development and pathology. Because class IIa HDAC catalytic activity is low, their exact molecular roles have not been fully elucidated. Studies have suggested that class IIa HDACs may serve as a scaffold to recruit the catalytically active class I HDAC complexes to their substrate. Here we directly address whether the class IIa HDAC, HDAC5 may function as a scaffold to recruit co-repressor complexes to promoters. We examined two well-characterized cardiac promoters, the sodium calcium exchanger (Ncx1) and the brain natriuretic peptide (Bnp) whose hypertrophic upregulation is mediated by both class I and IIa HDACs. Selective inhibition of class IIa HDACs did not prevent adrenergic stimulated Ncx1 upregulation, however HDAC5 knockout prevented pressure overload induced Ncx1 upregulation. Using the HDAC5((-/-)) mouse we show that HDAC5 is required for the interaction of the HDAC1/2/Sin3a co-repressor complexes with the Nkx2.5 and YY1 transcription factors and critical for recruitment of the HDAC1/Sin3a co-repressor complex to either the Ncx1 or Bnp promoter. Our novel findings support a non-canonical role of class IIa HDACs in the scaffolding of transcriptional regulatory complexes, which may be relevant for therapeutic intervention for pathologies.