ß3-adrenoceptor mediates metabolic protein remodeling in a rabbit model of tachypacing-induced atrial fibrillation.
Cell Physiol Biochem
; 32(6): 1631-42, 2013.
Article
em En
| MEDLINE
| ID: mdl-24335437
ABSTRACT
BACKGROUND:
The beta 3-adrenoceptor (ß3-AR) is closely associated with energy metabolism. This study aimed to explore the role of ß3-AR in energy remodeling in a rabbit model of pacing-induced atrial fibrillation (AF).METHODS:
Rabbits with a sham-operation or pacing-induced AF were used for this study, and the latter group was further divided into three subgroups 1) the pacing group, 2) the ß3-AR agonist (BRL37344)-treated group, and 3) the ß3-AR antagonist (SR59230A)-treated group. Atrial electrogram morphology and surface ECG were used to monitor the induction of AF and atrial effective refractory period (AERP). RT-PCR and western blot (WB) were used to show alterations in ß3-AR and metabolic-related protein.RESULTS:
RT-PCR and WB results showed that ß3-AR was significantly upregulated in the pacing group, and that it corresponded with high AF inducibility and significantly decreased AERP200 and ATP production in this group. Inhibition of ß3-AR decreased the AF induction rate, reversed AERP200 reduction, and restored ATP levels in the AF rabbits. Further activation of ß3-AR using agonist BRL37344 exacerbated AF-induced metabolic disruption. Periodic acid Schiff (PAS) and Oil Red O staining showed ß3-AR-dependent glycogen and lipid droplet accumulation in cardiac myocytes with AF. Glucose transporter-4 (GLUT-4) and CD36, key transporters of glucose and fatty acids, were downregulated in the pacing group. Expression of carnitine-palmitoyltransferase I (CPT-1), a key regulator in fatty acid metabolism, was also significantly downregulated in the pacing group. Reduced glucose transportation and fatty acid oxidation could be restored by inhibition of ß3-AR. Furthermore, key regulators of metabolism, peroxisome proliferator-activated receptor-α (PPARα) and PPAR co-activator (PGC-1α) can be regulated by pharmacological intervention of the ß3-AR.CONCLUSIONS:
ß3-AR is involved in metabolic protein remodeling in AF. PPARα/PGC-1α signaling pathway might be the relevant down-stream molecular machinery in response to AF-induced activation of ß3-AR. ß3-AR might be a novel target in AF treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Receptores Adrenérgicos beta 3
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China