Assessment of energetic costs of AhR activation by ß-naphthoflavone in rainbow trout (Oncorhynchus mykiss) hepatocytes using metabolic flux analysis.
Toxicol Appl Pharmacol
; 271(1): 86-94, 2013 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-23639520
ABSTRACT
Exposure to environmental contaminants such as activators of the aryl hydrocarbon receptor (AhR) leads to the induction of defense and detoxification mechanisms. While these mechanisms allow organisms to metabolize and excrete at least some of these environmental contaminants, it has been proposed that these mechanisms lead to significant energetic challenges. This study tests the hypothesis that activation of the AhR by the model agonist ß-naphthoflavone (ßNF) results in increased energetic costs in rainbow trout (Oncorhynchus mykiss) hepatocytes. To address this hypothesis, we employed traditional biochemical approaches to examine energy allocation and metabolism including the adenylate energy charge (AEC), protein synthesis rates, Na(+)/K(+)-ATPase activity, and enzyme activities. Moreover, we have used for the first time in a fish cell preparation, metabolic flux analysis (MFA) an in silico approach for the estimation of intracellular metabolic fluxes. Exposure of trout hepatocytes to 1µM ßNF for 48h did not alter hepatocyte AEC, protein synthesis, or Na(+)/K(+)-ATPase activity but did lead to sparing of glycogen reserves and changes in activities of alanine aminotransferase and citrate synthase suggesting altered metabolism. Conversely, MFA did not identify altered metabolic fluxes, although we do show that the dynamic metabolism of isolated trout hepatocytes poses a significant challenge for this type of approach which should be considered in future studies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Hidrocarboneto Arílico
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Oncorhynchus mykiss
/
Beta-Naftoflavona
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Hepatócitos
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Metabolismo Energético
Tipo de estudo:
Health_economic_evaluation
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá