PPARα agonist prevented the apoptosis induced by glucose and fatty acid in neonatal cardiomyocytes.
J Endocrinol Invest
; 34(4): 271-5, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-20354356
ABSTRACT
OBJECTIVE:
We investigated the effect of peroxisome proliferator activator receptors α (PPARα) on cardiomyocyte apoptosis induced by glucose and fatty acid, and if high glucose levels could increase fatty acid-induced apoptosis.METHODS:
Cardiomyocytes were maintained in Dulbecco's Modified Eagle Medium and divided into 5 groups Group N (control Group); Group G (exposed to 25.5 mmol/l glucose); Group L (exposed to 5 mmol/l glucose, fatty acid); Group H (exposed to 25.5 mmol/l glucose and fatty acid); Group I (exposed to 25.5 mmol/l glucose, fatty acid and Wy14643). Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Immunocytochemistry staining detected PPARα's expressing, and western blotting detected PPARα and nuclear factor κB's (NF-κB) protein level.RESULTS:
Exposure to fatty acid resulted in a significant increase of cardiomyocytes apoptosis, with the extension of NF-κB formation, whereas exposure to 25.5 mmol/l glucose had no influence on the apoptosis rate. However, combination with fatty acid and high glucose concentration had induced more apoptosis with the up-regulation of NF-κB formation. The fatty acid and glucose-induced effects were improved by Wy14643, with down-regulation of NF-κB formation.CONCLUSION:
These results suggested that in neonatal cardiomyocytes, fatty acid and glucose in combination with fatty acid induced apoptosis via NF-κB formation and activation of apoptosis pathways; glucose in combination with fatty acid induce more apoptosis rate for the more NF- κB formation, activation of the PPARα can reverse such apoptosis effect. The results also suggest that gluco-lipotoxicity may play a central role in the development of diabetic cardiomyopathy, and PPARα-agonist may be an effective drug in treating the diabetic cardiomyopathy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Apoptose
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Miócitos Cardíacos
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PPAR alfa
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Ácidos Graxos
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Glucose
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Endocrinol Invest
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
China